Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pathology > 4 - Diseases Of The Immune System > Flashcards

4 - Diseases Of The Immune System Flashcards

1
Q

Refers to the body’s protection against infection

A

Immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Composed of innate and adaptive components
Capable of causing tissue injury
May become exaggerated or depressed

A

Immune System

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Natural, present at birth, cells are always present, non-adapative

A

Innate immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Characterized by inflammation, antiviral defense and sending danger signals

A

Innate immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Major reaction of innate immune system

A

Inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Developed by exposure to pathogens, specific, normally silent

A

Adapative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Two components of adaptive immune system

A

Humoral

Cellular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Primary cells in humoral response

A

B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Primary cells in cellular response

A

T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Three broad categories of the diseases of the immune system

A
  1. Hypersensitivity reactions
  2. Autoimmune disease
  3. Immunologic deficiency syndromes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

A disease characterized by abnormal proteins from IgG that accumulates forming insoluble structures and exert obstructive and compressive effects

A

Amyloidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

A category of immune system disease that may be

1) elicited by both endogenous and exogenous substances
2) associated with particular susceptible genes
3) caused by imbalance between effector and control mechanisms

A

Hypersensitivity reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Exaggerated immune system

A

Hypersensitivity reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Depressed immune system

A

Immunologic deficiency syndromes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Self against self

A

Autoimmune diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Four types of hypersensitivity reactions

A

Type I: Immediate hypersensitivity
Type II: Antibody-mediated hypersensitivity
Type III: Immune complex mediated hypersensitivity
Type IV: T-cell mediated hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Type of hypersensitivity reactions characterized by rapidly developing immunologic reaction occurring within minutes after the combination of an antigen with antibody bund to mast cells in individuals previously sensitized to the antigen

A

Type I: Immediate hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Type I: Immediate hypersensitivity reaction is mediated by this antibody

A

IgE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Mechanism of type I: Immediate hypersensitivity reactions

A

Ag + IgE bound to mast cells or basophils ➡️ immediate release of vasoactive amines and other mediators from mast cells and recruitment of inflammatory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Mechanism of Type I: Immediate hypersensitivity reactions on re-exposure

A

Allergen binds and crosslink with IgE on mast cells results in:

  1. Release (degranulation) of preformed vesicles containing primary mediators
  2. De novo synthesis and release of secondary mediators
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Primary mediators of Type I: Immediate hypersensitivity reactions

A

Histamine, proteases, chemotactic factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Main mediator responsible for signs and symptoms of Type I: Immediate hypersensitivity reactions

A

Histamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Secondary mediators of Type I: Immediate hypersensitivity reactions

A

Leukotrienes B4, C4, D4 and prostaglandin D2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Two phases of Type I: Immediate hypersensitivity reactions

A
  1. Initial (rapid) response: 5-30mins

2. Second (delayed) phase: 2-24hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Mediators of initial response phase
Biogenic amines
26
Effect of biogenic amines
Bronchial smooth muscle contraction Increased vascular permeability and dilatation Increase mucous gland secretion
27
Mediators of second phase
Lipid mediators: LTB4, C4, D4 & E4, PGD2 and PAF | Cytokine mediators: TNF-alpha, IL-1,3,4,5,6, GM-CSF, chemokines
28
Effects of Leukotriene C4 and D4
Bronchial smooth muscle contraction | Increase permeability
29
Effects of prostaglandin D2
Bronchospasm | Increase mucous secretion
30
Caused tissue damage by releasing major basic protein and cationic proteins
Eosinophils
31
True or False. | Major basic protein and eosinophil cationic proteins are both toxic to epithelial cells.
True
32
Effects of IL-3,4,5,6 and GM-CSF
Promote activation of IgE and recruitment of eosinophils
33
True or False. | Mediators take action on antigen and cause the clinical presentation of allergy
True
34
Mediator that induces class switching of the lymphocytes to an IgE producing B cell
IL-4
35
Mediator that activated eosinophils and recruits them to site of infection
IL-5
36
Receptors where IgE crosslinks with mast cells
FCepsilonR1
37
Two subtypes of Type I: Immediate hypersensitivity reactions
1. Local immmediate hypersensitivity | 2. Systemic anaphylaxis
38
Subtype of Type I: Immediate hypersensitivity that affects a specific organ, exemplified by atopic allergies, and have hereditary predisposition
Local immediate hypersensitivity reactions
39
True or False. In local immediate hypersensitivity reactions, affected individuals tend to develop local type I responses to common allergens due to increase IgE and IL-4 producing TH2 cells.
True
40
Symptoms of local immediate hypersensitivity reactions
Utricaria, allergic rhinitis, asthma and nasal catarrh
41
Subtype of Type I: Immediate hypersensitivity that affects multiple organs, follows a parenteral or oral administration of an allergen (e.g. penicillin, peanuts, toxins, shellfish) and is more severe or may be fatal
Systemic anaphylaxis
42
Symptoms of systemic anaphylaxis
Pruritus, utricaria, erythema within minutes after exposure ➡️ bronchoconstriction, laryngeal edema, obstruction, hypotensive shock ➡️ death
43
Type of hypersensitivity reaction that is mediated by antibodies against intrinsic antigens or extrinsic agents adsorbed on cell surfaces or ECM
Type II: Antibody-mediated hypersensitivity reactions
44
Main antibodies involved in Type II: Antibody-mediated hypersensitivity reactions
IgG and IgM
45
Mechanism of Type II: Antibody-mediated hypersensitivity reactions
IgG or IgM + Ag bound to cell surface or ECM ➡️ phagocytosis and lysis ➡️ tissue injury due to inflammation
46
Three major pathways of Type II: Antibody-mediated hypersensitivity reactions
IIa. Opsonization, complement- and Fc-mediated phagocytosis IIb. Complement- and Fc-receptor-mediated inflammation IIc. Antibody-mediated cellular dysfunction
47
Components of the complement system that act as opsonins
C3b and C5b
48
True or False. Complement activation causes neutrophils and macrophages to attack Ag which release ROS and substances that induce inflammation
True
49
Autoimmune hemolytic anemia Target antigen: ________________ Mechanism: __________________
Target antigen: RBC membrane proteins | Mechanism: IIa opsonization and phagocytosis of erythrocytes
50
Autoimmune thrombocytopenia purpura Target antigen: ________________ Mechanism: __________________
Target antigen: Platelet membrane proteins (GpIIb:IIa or GpIb/IX) Mechanism: IIa opsonization and phagocytosis of platelets
51
Goodpasture syndrome Target antigen: ________________ Mechanism: __________________
Target antigen: Noncollagenous proteins in basement membrane of alveoli and glomeruli Mechanism: IIb complement and Fc receptor mediated inflammation
52
Myasthenia gravis Target antigen: ________________ Mechanism: __________________
Target antigen: Acetylcholine receptor | Mechanism: IIc Ab inhibits Ach binding; down-regulates receptor
53
``` Graves disease (hyperthyroidism) Target antigen: ________________ Mechanism: __________________ ```
Target antigen: TSH receptor | Mechanism: IIc Ab-mediated stimulation of TSH receptor
54
Insulin resistance DM Target antigen: ________________ Mechanism: __________________
Target antigen: Insulin receptor | Mechanism: IIc Ab inhibit binding of insulin
55
Acute Rheumatic Fever Target antigen: ________________ Mechanism: __________________
Target antigen: Streptococcal cell wall Ag (exogenous) Mechanism: Ab mistakes myocardial Ag as foreign; IIb Ab cross-reacts with host myocardial Ag ➡️ macrophage activation/inflammation
56
Mechanism of Type III: Immune-complex mediated hypersensitivity
Ag+Ab ➡️ Ag-Ab complexes in circulation will be deposited in various organs ➡️ activate complement (classical pathway) ➡️ attract neutrophils and macrophages ➡️ release lysosomal enzymes (elastases, collagenases) ➡️ vasculitis, glomerulonephritis, arthritis, rash, etc.
57
Two subtypes of Type III: Immune-complex mediated hypersensitivity
Local | Systemic
58
Common deposition of immune-complexes
Kidneys, joints, blood vessels and skin
59
True or False. | Immune complexes are hard to eliminate and may bond in the circulation or at site of deposition.
True
60
In this subtype of Type III: Immune-complex mediated hypersensitivity, circulating immune complexes are systemically deposited, particularly in organs that filter blood at high pressures
Systemic immune complex disease
61
Examples of systemic immune complex disease
Acute serum sickness | SLE
62
Clinical presentation of acute serum sickness
Arthritis, skin rash, fever | 4-5 days after admin of serum but may appear more rapidly with repeated injection of the serum
63
Phases of the pathogenesis of systemic immune complex disease
Phase I: Formation of Ag-Ab complexes in circulation Phase II: Deposition of immune complexes in various tissues Phase III: Inflammatory reaction at the sites of immune complex deposition and clinical features appear due to tissue injury 10 days after exposure
64
True or False. | During active phase, C3 levels are decrease because they are used.
True
65
Characteristics of local immune complex disease
Affects a particularly Arthus reaction Large immune complexes precipitate in the vessel walls causing disruption of blood flow and inflammation Visible edema with severe hemorrhage followed occassionally by ulceration of the skin
66
Morphologic manifestations of local immune complex disease
Acute vasculitis with fibrinoid necrosis of the vessel wall | Intense neutrophilic infiltration
67
Disease examples of Ab-mediated hypersensitivity
``` Autoimmune hemolytic anemia Autoimmune thrombocytopenia purpura Goodpasture syndrome Myasthenia gravis Graves disease Insulin resistance DM Acute rheumatic fever ```
68
Disease examples of immune-complex mediated hypersensitivity
``` SLE Polyarteritis nodosa Poststreptococcal glomerulonephritis Acute glomerulonephritis Arthus reaction Serum sickness ```
69
Localized are of tissue necrosis resulting from acute immune complex vasculitis, usually elicited in the skin
Arthus reaction
70
SLE Antigen involved: _______________ Manifestations: _______________
Antigen involved: DNA, nucleoproteins, others | Manifestations: Nephritis, arthritis, vasculitis, skin lesions
71
Polyarteritis nodosa Antigen involved: _______________ Manifestations: _______________
Antigen involved: Hep B surface antigen | Manifestations: Vasculitis
72
Poststreptococcal glomerulonephritis Antigen involved: _______________ Manifestations: _______________
Antigen involved: Streptococcal cell wall Ags, may be planted in GBM Manifestations: Nephritis
73
Acute glomerulonephritis Antigen involved: _______________ Manifestations: _______________
Antigen involved: Bacterial, parasite, tumor Ag | Manifestations: Nephritis
74
Arthus reaction Antigen involved: _______________ Manifestations: _______________
Antigen involved: Various foreign proteins | Manifestations: Cutaneous vasculitis
75
Serum sickness Antigen involved: _______________ Manifestations: _______________
Antigen involved: Various proteins (e.g. foreign serum) | Manifestations: Arthritis vasculitis, nephritis
76
This type of hypersensitivity reaction is initiated by Ag-activated (sensitized) lymphocytes
Type IV: T-cell mediated hypersensitivity
77
Two subtypes of Type IV: T-cell mediated hypersensitivity
Delayed type hypersensitivity | T-cell mediated cytotoxicity
78
This subtype of Type IV: T-cell mediated hypersensitivity reaction is a principal pattern of response to TB, fungi, protozoa, parasite, contact skin sensitivity and allograft rejection
Delayed type hypersensitivity
79
Cytokines release during delayed type hypersensitivity
IFN-gamma IL2 TNF and Lymphotoxin
80
Cytokine responsible for activation of macrophages
IFN-gamma
81
Cytokine responsible for the proliferation T cells
IL2
82
Cytokines that are responsible for the extravasation of lymphocytes & monocytes and granuloma formation
TNF and Lymphotoxins
83
The type of hypersensitivity reaction whose inflammatory response is the most destructive
Type IV: T-cell mediated hypersensitivity
84
True or False. | CD4+ T cells and macrophages are always partners.
True
85
True or False. | Sometimes, CD8+ T cells will play a role in producing cytokines to aid CD4+ T cells.
True
86
Major T-cell in delayed type hypersensitivity reactions
CD4+ T cells
87
Major T cell in T-cell mediated cytotoxicity
CD8+ T cell
88
Morphology of delayed type hypersensitivity reactions
Perivascular cuffing Perivascular infiltrate replaced by macrophages (after 2-3 weeks) with epithelioid cells Granuloma formation
89
Mechanism of delayed type hypersensitivity reaction
Ag ➡️ Proliferation and differentiation of CD4+ T cells (APCs produce IL-1,6,12,23 and IFN-gamma) ➡️ Differentiation from TH1 to TH17 subset ➡️ inflammation
90
Type IV: T-cell mediated hypersensitivity subtype that fights against virus, tumor cells and allograft rejection
T-cell mediated cytotoxicity
91
Mechanism of T-cell mediated cytotoxicity
1.
92
Protease that cleave and activate caspases
Granzyme
93
End result of T-cell mediated cytotoxicity
Apoptosis
94
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
95
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
96
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
97
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
98
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
99
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
100
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
101
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
102
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
103
Cells involved in acute humoral rejection
B cells and Abs
104
Type of rejection that occurs after months to years after transplantation
Chronic rejection
105
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
106
Clinical presentation of chronic rejection
Progressive organ dysfunction
107
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
108
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
109
TH cell subset that recruits more macrophages mononuclear cells
TH1
110
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
111
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
112
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
113
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
114
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
115
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
116
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
117
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
118
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
119
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
120
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
121
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
122
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
123
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
124
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
125
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
126
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
127
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
128
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
129
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
130
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
131
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
132
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
133
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
134
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
135
Most common cause of death in SLE
Renal failure
136
Second most common cause of death in SLE
Sepsis/infection
137
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
138
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
139
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
140
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
141
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
142
Non-erosive synovitis with little joint deformity in SLE
Arthritis
143
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
144
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
145
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
146
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
147
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
148
Characteristic FANA pattern of SLE
Peripheral pattern
149
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
150
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
151
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
152
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
153
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
154
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
155
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
156
Sjogren Syndrome in association with another autoimmune disease
Secondary form
157
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
158
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
159
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
160
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
161
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
162
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
163
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
164
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
165
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
166
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
167
Calcium deposit in the skin
Calcinosis
168
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
169
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
170
Skin thickening of the fingers
Sclerodactyly
171
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
172
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
173
Two types of immunodeficiency
Primary | Secondary
174
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
175
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
176
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
177
Differentiation of mature plasma cells which requires T cells
Class switching
178
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
179
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
180
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
181
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
182
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
183
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
184
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
185
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
186
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
187
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
188
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
189
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
190
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
191
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
192
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
193
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
194
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
195
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
196
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
197
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
198
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
199
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
200
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
201
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
202
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
203
Promote survival and differentiation of B cells
BAFF
204
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
205
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
206
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
207
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
208
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
209
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
210
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
211
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
212
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
213
Clinical manifestation of C2 deficiency
Associated with bacterial infections
214
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
215
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
216
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
217
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
218
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
219
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
220
Two major target of HIV
Immune system and CNS
221
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
222
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
223
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
224
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
225
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
226
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
227
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
228
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
229
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
230
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
231
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
232
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
233
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
234
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
235
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
236
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
237
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
238
Group of diseases common of having deposition of amyloids
Amyloidosis
239
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
240
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
241
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
242
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
243
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
244
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
245
Morphology of Amyloidosis in the heart
Subendocardial deposits
246
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
247
Protease that cleave and activate caspases
Granzyme
248
End result of T-cell mediated cytotoxicity
Apoptosis
249
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
250
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
251
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
252
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
253
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
254
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
255
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
256
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
257
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
258
Cells involved in acute humoral rejection
B cells and Abs
259
Type of rejection that occurs after months to years after transplantation
Chronic rejection
260
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
261
Clinical presentation of chronic rejection
Progressive organ dysfunction
262
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
263
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
264
TH cell subset that recruits more macrophages mononuclear cells
TH1
265
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
266
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
267
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
268
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
269
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
270
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
271
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
272
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
273
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
274
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
275
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
276
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
277
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
278
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
279
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
280
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
281
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
282
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
283
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
284
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
285
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
286
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
287
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
288
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
289
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
290
Most common cause of death in SLE
Renal failure
291
Second most common cause of death in SLE
Sepsis/infection
292
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
293
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
294
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
295
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
296
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
297
Non-erosive synovitis with little joint deformity in SLE
Arthritis
298
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
299
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
300
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
301
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
302
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
303
Characteristic FANA pattern of SLE
Peripheral pattern
304
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
305
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
306
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
307
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
308
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
309
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
310
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
311
Sjogren Syndrome in association with another autoimmune disease
Secondary form
312
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
313
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
314
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
315
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
316
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
317
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
318
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
319
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
320
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
321
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
322
Calcium deposit in the skin
Calcinosis
323
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
324
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
325
Skin thickening of the fingers
Sclerodactyly
326
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
327
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
328
Two types of immunodeficiency
Primary | Secondary
329
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
330
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
331
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
332
Differentiation of mature plasma cells which requires T cells
Class switching
333
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
334
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
335
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
336
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
337
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
338
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
339
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
340
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
341
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
342
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
343
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
344
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
345
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
346
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
347
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
348
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
349
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
350
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
351
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
352
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
353
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
354
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
355
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
356
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
357
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
358
Promote survival and differentiation of B cells
BAFF
359
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
360
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
361
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
362
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
363
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
364
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
365
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
366
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
367
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
368
Clinical manifestation of C2 deficiency
Associated with bacterial infections
369
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
370
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
371
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
372
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
373
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
374
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
375
Two major target of HIV
Immune system and CNS
376
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
377
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
378
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
379
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
380
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
381
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
382
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
383
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
384
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
385
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
386
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
387
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
388
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
389
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
390
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
391
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
392
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
393
Group of diseases common of having deposition of amyloids
Amyloidosis
394
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
395
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
396
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
397
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
398
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
399
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
400
Morphology of Amyloidosis in the heart
Subendocardial deposits
401
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
402
Protease that cleave and activate caspases
Granzyme
403
End result of T-cell mediated cytotoxicity
Apoptosis
404
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
405
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
406
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
407
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
408
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
409
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
410
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
411
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
412
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
413
Cells involved in acute humoral rejection
B cells and Abs
414
Type of rejection that occurs after months to years after transplantation
Chronic rejection
415
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
416
Clinical presentation of chronic rejection
Progressive organ dysfunction
417
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
418
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
419
TH cell subset that recruits more macrophages mononuclear cells
TH1
420
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
421
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
422
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
423
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
424
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
425
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
426
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
427
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
428
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
429
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
430
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
431
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
432
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
433
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
434
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
435
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
436
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
437
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
438
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
439
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
440
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
441
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
442
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
443
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
444
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
445
Most common cause of death in SLE
Renal failure
446
Second most common cause of death in SLE
Sepsis/infection
447
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
448
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
449
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
450
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
451
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
452
Non-erosive synovitis with little joint deformity in SLE
Arthritis
453
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
454
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
455
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
456
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
457
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
458
Characteristic FANA pattern of SLE
Peripheral pattern
459
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
460
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
461
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
462
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
463
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
464
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
465
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
466
Sjogren Syndrome in association with another autoimmune disease
Secondary form
467
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
468
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
469
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
470
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
471
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
472
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
473
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
474
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
475
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
476
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
477
Calcium deposit in the skin
Calcinosis
478
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
479
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
480
Skin thickening of the fingers
Sclerodactyly
481
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
482
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
483
Two types of immunodeficiency
Primary | Secondary
484
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
485
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
486
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
487
Differentiation of mature plasma cells which requires T cells
Class switching
488
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
489
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
490
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
491
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
492
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
493
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
494
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
495
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
496
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
497
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
498
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
499
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
500
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
501
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
502
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
503
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
504
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
505
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
506
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
507
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
508
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
509
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
510
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
511
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
512
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
513
Promote survival and differentiation of B cells
BAFF
514
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
515
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
516
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
517
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
518
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
519
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
520
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
521
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
522
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
523
Clinical manifestation of C2 deficiency
Associated with bacterial infections
524
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
525
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
526
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
527
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
528
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
529
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
530
Two major target of HIV
Immune system and CNS
531
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
532
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
533
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
534
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
535
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
536
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
537
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
538
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
539
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
540
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
541
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
542
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
543
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
544
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
545
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
546
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
547
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
548
Group of diseases common of having deposition of amyloids
Amyloidosis
549
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
550
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
551
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
552
Morphology of Amyloidosis in the heart
Subendocardial deposits
553
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
554
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
555
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
556
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
557
Protease that cleave and activate caspases
Granzyme
558
End result of T-cell mediated cytotoxicity
Apoptosis
559
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
560
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
561
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
562
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
563
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
564
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
565
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
566
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
567
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
568
Cells involved in acute humoral rejection
B cells and Abs
569
Type of rejection that occurs after months to years after transplantation
Chronic rejection
570
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
571
Clinical presentation of chronic rejection
Progressive organ dysfunction
572
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
573
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
574
TH cell subset that recruits more macrophages mononuclear cells
TH1
575
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
576
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
577
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
578
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
579
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
580
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
581
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
582
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
583
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
584
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
585
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
586
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
587
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
588
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
589
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
590
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
591
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
592
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
593
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
594
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
595
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
596
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
597
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
598
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
599
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
600
Most common cause of death in SLE
Renal failure
601
Second most common cause of death in SLE
Sepsis/infection
602
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
603
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
604
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
605
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
606
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
607
Non-erosive synovitis with little joint deformity in SLE
Arthritis
608
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
609
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
610
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
611
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
612
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
613
Characteristic FANA pattern of SLE
Peripheral pattern
614
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
615
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
616
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
617
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
618
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
619
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
620
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
621
Sjogren Syndrome in association with another autoimmune disease
Secondary form
622
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
623
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
624
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
625
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
626
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
627
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
628
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
629
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
630
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
631
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
632
Calcium deposit in the skin
Calcinosis
633
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
634
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
635
Skin thickening of the fingers
Sclerodactyly
636
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
637
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
638
Two types of immunodeficiency
Primary | Secondary
639
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
640
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
641
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
642
Differentiation of mature plasma cells which requires T cells
Class switching
643
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
644
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
645
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
646
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
647
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
648
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
649
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
650
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
651
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
652
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
653
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
654
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
655
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
656
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
657
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
658
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
659
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
660
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
661
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
662
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
663
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
664
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
665
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
666
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
667
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
668
Promote survival and differentiation of B cells
BAFF
669
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
670
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
671
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
672
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
673
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
674
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
675
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
676
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
677
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
678
Clinical manifestation of C2 deficiency
Associated with bacterial infections
679
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
680
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
681
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
682
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
683
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
684
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
685
Two major target of HIV
Immune system and CNS
686
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
687
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
688
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
689
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
690
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
691
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
692
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
693
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
694
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
695
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
696
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
697
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
698
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
699
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
700
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
701
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
702
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
703
Group of diseases common of having deposition of amyloids
Amyloidosis
704
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
705
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
706
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
707
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
708
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
709
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
710
Morphology of Amyloidosis in the heart
Subendocardial deposits
711
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
712
Protease that cleave and activate caspases
Granzyme
713
End result of T-cell mediated cytotoxicity
Apoptosis
714
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
715
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
716
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
717
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
718
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
719
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
720
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
721
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
722
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
723
Cells involved in acute humoral rejection
B cells and Abs
724
Type of rejection that occurs after months to years after transplantation
Chronic rejection
725
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
726
Clinical presentation of chronic rejection
Progressive organ dysfunction
727
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
728
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
729
TH cell subset that recruits more macrophages mononuclear cells
TH1
730
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
731
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
732
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
733
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
734
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
735
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
736
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
737
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
738
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
739
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
740
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
741
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
742
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
743
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
744
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
745
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
746
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
747
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
748
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
749
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
750
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
751
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
752
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
753
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
754
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
755
Most common cause of death in SLE
Renal failure
756
Second most common cause of death in SLE
Sepsis/infection
757
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
758
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
759
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
760
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
761
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
762
Non-erosive synovitis with little joint deformity in SLE
Arthritis
763
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
764
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
765
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
766
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
767
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
768
Characteristic FANA pattern of SLE
Peripheral pattern
769
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
770
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
771
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
772
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
773
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
774
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
775
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
776
Sjogren Syndrome in association with another autoimmune disease
Secondary form
777
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
778
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
779
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
780
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
781
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
782
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
783
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
784
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
785
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
786
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
787
Calcium deposit in the skin
Calcinosis
788
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
789
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
790
Skin thickening of the fingers
Sclerodactyly
791
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
792
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
793
Two types of immunodeficiency
Primary | Secondary
794
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
795
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
796
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
797
Differentiation of mature plasma cells which requires T cells
Class switching
798
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
799
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
800
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
801
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
802
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
803
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
804
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
805
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
806
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
807
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
808
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
809
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
810
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
811
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
812
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
813
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
814
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
815
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
816
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
817
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
818
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
819
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
820
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
821
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
822
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
823
Promote survival and differentiation of B cells
BAFF
824
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
825
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
826
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
827
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
828
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
829
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
830
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
831
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
832
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
833
Clinical manifestation of C2 deficiency
Associated with bacterial infections
834
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
835
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
836
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
837
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
838
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
839
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
840
Two major target of HIV
Immune system and CNS
841
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
842
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
843
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
844
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
845
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
846
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
847
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
848
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
849
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
850
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
851
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
852
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
853
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
854
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
855
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
856
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
857
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
858
Group of diseases common of having deposition of amyloids
Amyloidosis
859
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
860
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
861
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
862
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
863
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
864
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
865
Morphology of Amyloidosis in the heart
Subendocardial deposits
866
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
867
Protease that cleave and activate caspases
Granzyme
868
End result of T-cell mediated cytotoxicity
Apoptosis
869
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
870
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
871
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
872
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
873
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
874
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
875
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
876
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
877
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
878
Cells involved in acute humoral rejection
B cells and Abs
879
Type of rejection that occurs after months to years after transplantation
Chronic rejection
880
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
881
Clinical presentation of chronic rejection
Progressive organ dysfunction
882
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
883
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
884
TH cell subset that recruits more macrophages mononuclear cells
TH1
885
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
886
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
887
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
888
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
889
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
890
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
891
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
892
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
893
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
894
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
895
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
896
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
897
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
898
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
899
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
900
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
901
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
902
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
903
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
904
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
905
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
906
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
907
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
908
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
909
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
910
Most common cause of death in SLE
Renal failure
911
Second most common cause of death in SLE
Sepsis/infection
912
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
913
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
914
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
915
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
916
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
917
Non-erosive synovitis with little joint deformity in SLE
Arthritis
918
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
919
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
920
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
921
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
922
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
923
Characteristic FANA pattern of SLE
Peripheral pattern
924
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
925
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
926
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
927
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
928
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
929
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
930
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
931
Sjogren Syndrome in association with another autoimmune disease
Secondary form
932
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
933
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
934
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
935
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
936
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
937
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
938
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
939
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
940
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
941
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
942
Calcium deposit in the skin
Calcinosis
943
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
944
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
945
Skin thickening of the fingers
Sclerodactyly
946
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
947
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
948
Two types of immunodeficiency
Primary | Secondary
949
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
950
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
951
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
952
Differentiation of mature plasma cells which requires T cells
Class switching
953
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
954
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
955
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
956
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
957
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
958
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
959
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
960
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
961
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
962
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
963
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
964
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
965
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
966
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
967
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
968
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
969
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
970
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
971
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
972
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
973
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
974
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
975
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
976
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
977
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
978
Promote survival and differentiation of B cells
BAFF
979
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
980
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
981
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
982
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
983
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
984
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
985
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
986
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
987
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
988
Clinical manifestation of C2 deficiency
Associated with bacterial infections
989
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
990
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
991
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
992
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
993
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
994
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
995
Two major target of HIV
Immune system and CNS
996
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
997
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
998
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
999
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1000
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1001
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1002
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1003
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1004
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1005
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1006
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1007
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1008
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1009
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1010
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1011
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1012
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1013
Group of diseases common of having deposition of amyloids
Amyloidosis
1014
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1015
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1016
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1017
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1018
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1019
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1020
Morphology of Amyloidosis in the heart
Subendocardial deposits
1021
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1022
Protease that cleave and activate caspases
Granzyme
1023
End result of T-cell mediated cytotoxicity
Apoptosis
1024
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1025
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1026
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1027
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1028
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1029
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1030
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1031
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1032
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1033
Cells involved in acute humoral rejection
B cells and Abs
1034
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1035
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1036
Clinical presentation of chronic rejection
Progressive organ dysfunction
1037
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1038
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1039
TH cell subset that recruits more macrophages mononuclear cells
TH1
1040
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1041
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1042
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1043
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1044
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1045
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1046
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1047
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1048
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1049
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1050
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1051
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1052
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1053
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1054
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1055
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1056
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1057
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1058
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1059
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1060
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1061
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1062
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1063
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1064
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1065
Most common cause of death in SLE
Renal failure
1066
Second most common cause of death in SLE
Sepsis/infection
1067
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1068
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1069
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
1070
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
1071
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
1072
Non-erosive synovitis with little joint deformity in SLE
Arthritis
1073
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
1074
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
1075
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
1076
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
1077
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
1078
Characteristic FANA pattern of SLE
Peripheral pattern
1079
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
1080
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
1081
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
1082
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
1083
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
1084
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
1085
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
1086
Sjogren Syndrome in association with another autoimmune disease
Secondary form
1087
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
1088
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
1089
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
1090
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
1091
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
1092
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
1093
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
1094
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
1095
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
1096
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
1097
Calcium deposit in the skin
Calcinosis
1098
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
1099
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
1100
Skin thickening of the fingers
Sclerodactyly
1101
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
1102
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
1103
Two types of immunodeficiency
Primary | Secondary
1104
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
1105
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
1106
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
1107
Differentiation of mature plasma cells which requires T cells
Class switching
1108
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
1109
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
1110
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
1111
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
1112
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
1113
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
1114
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
1115
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
1116
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
1117
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
1118
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
1119
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
1120
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
1121
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
1122
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
1123
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
1124
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
1125
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
1126
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
1127
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
1128
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
1129
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
1130
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
1131
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
1132
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
1133
Promote survival and differentiation of B cells
BAFF
1134
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
1135
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
1136
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
1137
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
1138
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
1139
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
1140
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
1141
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
1142
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
1143
Clinical manifestation of C2 deficiency
Associated with bacterial infections
1144
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
1145
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
1146
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
1147
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
1148
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
1149
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
1150
Two major target of HIV
Immune system and CNS
1151
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
1152
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
1153
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
1154
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1155
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1156
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1157
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1158
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1159
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1160
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1161
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1162
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1163
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1164
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1165
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1166
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1167
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1168
Group of diseases common of having deposition of amyloids
Amyloidosis
1169
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1170
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1171
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1172
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1173
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1174
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1175
Morphology of Amyloidosis in the heart
Subendocardial deposits
1176
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1177
Protease that cleave and activate caspases
Granzyme
1178
End result of T-cell mediated cytotoxicity
Apoptosis
1179
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1180
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1181
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1182
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1183
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1184
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1185
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1186
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1187
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1188
Cells involved in acute humoral rejection
B cells and Abs
1189
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1190
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1191
Clinical presentation of chronic rejection
Progressive organ dysfunction
1192
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1193
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1194
TH cell subset that recruits more macrophages mononuclear cells
TH1
1195
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1196
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1197
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1198
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1199
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1200
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1201
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1202
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1203
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1204
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1205
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1206
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1207
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1208
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1209
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1210
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1211
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1212
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1213
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1214
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1215
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1216
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1217
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1218
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1219
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1220
Most common cause of death in SLE
Renal failure
1221
Second most common cause of death in SLE
Sepsis/infection
1222
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1223
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1224
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
1225
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
1226
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
1227
Non-erosive synovitis with little joint deformity in SLE
Arthritis
1228
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
1229
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
1230
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
1231
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
1232
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
1233
Characteristic FANA pattern of SLE
Peripheral pattern
1234
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
1235
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
1236
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
1237
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
1238
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
1239
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
1240
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
1241
Sjogren Syndrome in association with another autoimmune disease
Secondary form
1242
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
1243
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
1244
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
1245
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
1246
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
1247
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
1248
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
1249
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
1250
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
1251
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
1252
Calcium deposit in the skin
Calcinosis
1253
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
1254
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
1255
Skin thickening of the fingers
Sclerodactyly
1256
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
1257
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
1258
Two types of immunodeficiency
Primary | Secondary
1259
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
1260
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
1261
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
1262
Differentiation of mature plasma cells which requires T cells
Class switching
1263
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
1264
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
1265
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
1266
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
1267
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
1268
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
1269
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
1270
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
1271
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
1272
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
1273
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
1274
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
1275
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
1276
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
1277
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
1278
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
1279
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
1280
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
1281
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
1282
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
1283
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
1284
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
1285
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
1286
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
1287
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
1288
Promote survival and differentiation of B cells
BAFF
1289
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
1290
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
1291
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
1292
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
1293
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
1294
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
1295
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
1296
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
1297
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
1298
Clinical manifestation of C2 deficiency
Associated with bacterial infections
1299
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
1300
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
1301
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
1302
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
1303
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
1304
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
1305
Two major target of HIV
Immune system and CNS
1306
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
1307
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
1308
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
1309
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1310
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1311
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1312
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1313
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1314
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1315
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1316
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1317
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1318
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1319
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1320
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1321
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1322
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1323
Group of diseases common of having deposition of amyloids
Amyloidosis
1324
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1325
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1326
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1327
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1328
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1329
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1330
Morphology of Amyloidosis in the heart
Subendocardial deposits
1331
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1332
Protease that cleave and activate caspases
Granzyme
1333
End result of T-cell mediated cytotoxicity
Apoptosis
1334
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1335
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1336
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1337
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1338
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1339
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1340
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1341
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1342
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1343
Cells involved in acute humoral rejection
B cells and Abs
1344
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1345
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1346
Clinical presentation of chronic rejection
Progressive organ dysfunction
1347
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1348
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1349
TH cell subset that recruits more macrophages mononuclear cells
TH1
1350
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1351
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1352
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1353
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1354
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1355
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1356
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1357
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1358
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1359
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1360
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1361
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1362
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1363
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1364
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1365
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1366
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1367
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1368
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1369
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1370
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1371
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1372
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1373
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1374
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1375
Most common cause of death in SLE
Renal failure
1376
Second most common cause of death in SLE
Sepsis/infection
1377
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1378
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1379
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
1380
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
1381
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
1382
Non-erosive synovitis with little joint deformity in SLE
Arthritis
1383
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
1384
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
1385
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
1386
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
1387
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
1388
Characteristic FANA pattern of SLE
Peripheral pattern
1389
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
1390
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
1391
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
1392
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
1393
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
1394
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
1395
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
1396
Sjogren Syndrome in association with another autoimmune disease
Secondary form
1397
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
1398
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
1399
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
1400
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
1401
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
1402
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
1403
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
1404
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
1405
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
1406
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
1407
Calcium deposit in the skin
Calcinosis
1408
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
1409
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
1410
Skin thickening of the fingers
Sclerodactyly
1411
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
1412
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
1413
Two types of immunodeficiency
Primary | Secondary
1414
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
1415
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
1416
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
1417
Differentiation of mature plasma cells which requires T cells
Class switching
1418
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
1419
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
1420
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
1421
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
1422
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
1423
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
1424
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
1425
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
1426
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
1427
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
1428
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
1429
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
1430
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
1431
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
1432
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
1433
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
1434
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
1435
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
1436
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
1437
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
1438
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
1439
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
1440
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
1441
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
1442
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
1443
Promote survival and differentiation of B cells
BAFF
1444
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
1445
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
1446
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
1447
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
1448
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
1449
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
1450
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
1451
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
1452
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
1453
Clinical manifestation of C2 deficiency
Associated with bacterial infections
1454
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
1455
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
1456
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
1457
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
1458
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
1459
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
1460
Two major target of HIV
Immune system and CNS
1461
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
1462
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
1463
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
1464
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1465
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1466
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1467
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1468
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1469
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1470
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1471
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1472
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1473
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1474
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1475
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1476
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1477
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1478
Group of diseases common of having deposition of amyloids
Amyloidosis
1479
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1480
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1481
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1482
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1483
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1484
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1485
Morphology of Amyloidosis in the heart
Subendocardial deposits
1486
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1487
Protease that cleave and activate caspases
Granzyme
1488
End result of T-cell mediated cytotoxicity
Apoptosis
1489
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1490
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1491
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1492
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1493
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1494
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1495
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1496
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1497
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1498
Cells involved in acute humoral rejection
B cells and Abs
1499
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1500
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1501
Clinical presentation of chronic rejection
Progressive organ dysfunction
1502
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1503
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1504
TH cell subset that recruits more macrophages mononuclear cells
TH1
1505
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1506
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1507
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1508
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1509
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1510
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1511
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1512
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1513
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1514
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1515
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1516
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1517
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1518
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1519
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1520
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1521
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1522
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1523
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1524
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1525
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1526
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1527
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1528
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1529
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1530
Most common cause of death in SLE
Renal failure
1531
Second most common cause of death in SLE
Sepsis/infection
1532
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1533
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1534
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
1535
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
1536
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
1537
Non-erosive synovitis with little joint deformity in SLE
Arthritis
1538
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
1539
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
1540
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
1541
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
1542
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
1543
Characteristic FANA pattern of SLE
Peripheral pattern
1544
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
1545
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
1546
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
1547
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
1548
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
1549
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
1550
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
1551
Sjogren Syndrome in association with another autoimmune disease
Secondary form
1552
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
1553
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
1554
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
1555
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
1556
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
1557
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
1558
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
1559
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
1560
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
1561
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
1562
Calcium deposit in the skin
Calcinosis
1563
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
1564
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
1565
Skin thickening of the fingers
Sclerodactyly
1566
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
1567
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
1568
Two types of immunodeficiency
Primary | Secondary
1569
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
1570
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
1571
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
1572
Differentiation of mature plasma cells which requires T cells
Class switching
1573
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
1574
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
1575
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
1576
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
1577
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
1578
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
1579
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
1580
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
1581
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
1582
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
1583
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
1584
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
1585
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
1586
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
1587
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
1588
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
1589
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
1590
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
1591
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
1592
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
1593
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
1594
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
1595
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
1596
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
1597
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
1598
Promote survival and differentiation of B cells
BAFF
1599
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
1600
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
1601
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
1602
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
1603
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
1604
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
1605
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
1606
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
1607
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
1608
Clinical manifestation of C2 deficiency
Associated with bacterial infections
1609
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
1610
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
1611
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
1612
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
1613
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
1614
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
1615
Two major target of HIV
Immune system and CNS
1616
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
1617
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
1618
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
1619
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1620
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1621
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1622
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1623
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1624
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1625
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1626
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1627
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1628
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1629
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1630
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1631
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1632
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1633
Group of diseases common of having deposition of amyloids
Amyloidosis
1634
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1635
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1636
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1637
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1638
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1639
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1640
Morphology of Amyloidosis in the heart
Subendocardial deposits
1641
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1642
Protease that cleave and activate caspases
Granzyme
1643
End result of T-cell mediated cytotoxicity
Apoptosis
1644
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1645
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1646
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1647
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1648
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1649
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1650
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1651
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1652
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1653
Cells involved in acute humoral rejection
B cells and Abs
1654
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1655
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1656
Clinical presentation of chronic rejection
Progressive organ dysfunction
1657
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1658
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1659
TH cell subset that recruits more macrophages mononuclear cells
TH1
1660
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1661
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1662
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1663
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1664
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1665
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1666
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1667
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1668
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1669
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1670
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1671
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1672
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1673
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1674
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1675
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1676
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1677
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1678
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1679
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1680
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1681
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1682
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1683
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1684
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1685
Most common cause of death in SLE
Renal failure
1686
Second most common cause of death in SLE
Sepsis/infection
1687
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1688
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1689
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
1690
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
1691
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
1692
Non-erosive synovitis with little joint deformity in SLE
Arthritis
1693
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
1694
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
1695
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
1696
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
1697
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
1698
Characteristic FANA pattern of SLE
Peripheral pattern
1699
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
1700
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
1701
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
1702
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
1703
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
1704
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
1705
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
1706
Sjogren Syndrome in association with another autoimmune disease
Secondary form
1707
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
1708
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
1709
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
1710
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
1711
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
1712
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
1713
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
1714
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
1715
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
1716
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
1717
Calcium deposit in the skin
Calcinosis
1718
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
1719
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
1720
Skin thickening of the fingers
Sclerodactyly
1721
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
1722
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
1723
Two types of immunodeficiency
Primary | Secondary
1724
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
1725
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
1726
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
1727
Differentiation of mature plasma cells which requires T cells
Class switching
1728
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
1729
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
1730
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
1731
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
1732
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
1733
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
1734
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
1735
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
1736
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
1737
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
1738
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
1739
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
1740
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
1741
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
1742
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
1743
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
1744
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
1745
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
1746
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
1747
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
1748
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
1749
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
1750
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
1751
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
1752
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
1753
Promote survival and differentiation of B cells
BAFF
1754
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
1755
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
1756
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
1757
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
1758
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
1759
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
1760
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
1761
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
1762
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
1763
Clinical manifestation of C2 deficiency
Associated with bacterial infections
1764
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
1765
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
1766
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
1767
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
1768
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
1769
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
1770
Two major target of HIV
Immune system and CNS
1771
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
1772
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
1773
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
1774
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1775
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1776
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1777
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1778
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1779
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1780
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1781
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1782
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1783
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1784
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1785
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1786
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1787
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1788
Group of diseases common of having deposition of amyloids
Amyloidosis
1789
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1790
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1791
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1792
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1793
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1794
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1795
Morphology of Amyloidosis in the heart
Subendocardial deposits
1796
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1797
Protease that cleave and activate caspases
Granzyme
1798
End result of T-cell mediated cytotoxicity
Apoptosis
1799
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1800
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1801
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1802
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1803
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1804
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1805
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1806
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1807
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1808
Cells involved in acute humoral rejection
B cells and Abs
1809
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1810
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1811
Clinical presentation of chronic rejection
Progressive organ dysfunction
1812
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1813
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1814
TH cell subset that recruits more macrophages mononuclear cells
TH1
1815
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1816
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1817
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1818
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1819
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1820
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1821
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1822
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1823
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1824
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1825
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1826
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1827
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1828
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1829
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1830
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1831
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1832
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1833
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1834
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1835
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1836
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1837
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1838
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1839
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1840
Most common cause of death in SLE
Renal failure
1841
Second most common cause of death in SLE
Sepsis/infection
1842
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1843
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1844
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
1845
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
1846
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
1847
Non-erosive synovitis with little joint deformity in SLE
Arthritis
1848
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
1849
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
1850
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
1851
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
1852
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
1853
Characteristic FANA pattern of SLE
Peripheral pattern
1854
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
1855
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
1856
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
1857
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
1858
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
1859
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
1860
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
1861
Sjogren Syndrome in association with another autoimmune disease
Secondary form
1862
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
1863
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
1864
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
1865
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
1866
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
1867
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
1868
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
1869
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
1870
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
1871
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
1872
Calcium deposit in the skin
Calcinosis
1873
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
1874
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
1875
Skin thickening of the fingers
Sclerodactyly
1876
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
1877
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
1878
Two types of immunodeficiency
Primary | Secondary
1879
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
1880
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
1881
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
1882
Differentiation of mature plasma cells which requires T cells
Class switching
1883
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
1884
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
1885
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
1886
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
1887
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
1888
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
1889
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
1890
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
1891
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
1892
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
1893
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
1894
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
1895
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
1896
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
1897
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
1898
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
1899
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
1900
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
1901
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
1902
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
1903
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
1904
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
1905
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
1906
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
1907
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
1908
Promote survival and differentiation of B cells
BAFF
1909
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
1910
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
1911
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
1912
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
1913
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
1914
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
1915
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
1916
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
1917
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
1918
Clinical manifestation of C2 deficiency
Associated with bacterial infections
1919
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
1920
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
1921
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
1922
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
1923
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
1924
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
1925
Two major target of HIV
Immune system and CNS
1926
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
1927
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
1928
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
1929
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
1930
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
1931
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
1932
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
1933
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
1934
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
1935
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
1936
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
1937
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
1938
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
1939
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
1940
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
1941
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
1942
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
1943
Group of diseases common of having deposition of amyloids
Amyloidosis
1944
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
1945
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
1946
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
1947
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
1948
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
1949
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
1950
Morphology of Amyloidosis in the heart
Subendocardial deposits
1951
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
1952
Protease that cleave and activate caspases
Granzyme
1953
End result of T-cell mediated cytotoxicity
Apoptosis
1954
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
1955
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
1956
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
1957
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
1958
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
1959
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
1960
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
1961
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
1962
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
1963
Cells involved in acute humoral rejection
B cells and Abs
1964
Type of rejection that occurs after months to years after transplantation
Chronic rejection
1965
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
1966
Clinical presentation of chronic rejection
Progressive organ dysfunction
1967
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
1968
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
1969
TH cell subset that recruits more macrophages mononuclear cells
TH1
1970
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
1971
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
1972
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
1973
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
1974
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
1975
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
1976
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
1977
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
1978
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
1979
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
1980
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
1981
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
1982
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
1983
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
1984
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
1985
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
1986
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
1987
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
1988
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
1989
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
1990
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
1991
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
1992
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
1993
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
1994
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
1995
Most common cause of death in SLE
Renal failure
1996
Second most common cause of death in SLE
Sepsis/infection
1997
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
1998
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
1999
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2000
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2001
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2002
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2003
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2004
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2005
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2006
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2007
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2008
Characteristic FANA pattern of SLE
Peripheral pattern
2009
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2010
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2011
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2012
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2013
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2014
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2015
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2016
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2017
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2018
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2019
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2020
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2021
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2022
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2023
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2024
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2025
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2026
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2027
Calcium deposit in the skin
Calcinosis
2028
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2029
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2030
Skin thickening of the fingers
Sclerodactyly
2031
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2032
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2033
Two types of immunodeficiency
Primary | Secondary
2034
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2035
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2036
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2037
Differentiation of mature plasma cells which requires T cells
Class switching
2038
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2039
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2040
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2041
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2042
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2043
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2044
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2045
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2046
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2047
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2048
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2049
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2050
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2051
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2052
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2053
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2054
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2055
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2056
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2057
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2058
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2059
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2060
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2061
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2062
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2063
Promote survival and differentiation of B cells
BAFF
2064
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2065
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2066
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2067
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2068
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2069
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
2070
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
2071
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
2072
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
2073
Clinical manifestation of C2 deficiency
Associated with bacterial infections
2074
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
2075
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
2076
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
2077
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
2078
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
2079
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
2080
Two major target of HIV
Immune system and CNS
2081
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
2082
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
2083
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
2084
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
2085
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
2086
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
2087
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
2088
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
2089
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
2090
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
2091
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
2092
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
2093
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
2094
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
2095
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
2096
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
2097
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
2098
Group of diseases common of having deposition of amyloids
Amyloidosis
2099
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
2100
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
2101
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
2102
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
2103
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
2104
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
2105
Morphology of Amyloidosis in the heart
Subendocardial deposits
2106
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
2107
Protease that cleave and activate caspases
Granzyme
2108
End result of T-cell mediated cytotoxicity
Apoptosis
2109
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
2110
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
2111
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
2112
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
2113
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
2114
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
2115
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
2116
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
2117
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
2118
Cells involved in acute humoral rejection
B cells and Abs
2119
Type of rejection that occurs after months to years after transplantation
Chronic rejection
2120
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
2121
Clinical presentation of chronic rejection
Progressive organ dysfunction
2122
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
2123
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
2124
TH cell subset that recruits more macrophages mononuclear cells
TH1
2125
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
2126
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
2127
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
2128
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
2129
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
2130
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
2131
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
2132
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
2133
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
2134
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
2135
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
2136
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
2137
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
2138
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
2139
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
2140
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
2141
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
2142
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
2143
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
2144
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
2145
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
2146
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
2147
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
2148
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
2149
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
2150
Most common cause of death in SLE
Renal failure
2151
Second most common cause of death in SLE
Sepsis/infection
2152
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
2153
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
2154
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2155
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2156
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2157
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2158
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2159
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2160
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2161
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2162
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2163
Characteristic FANA pattern of SLE
Peripheral pattern
2164
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2165
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2166
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2167
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2168
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2169
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2170
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2171
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2172
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2173
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2174
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2175
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2176
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2177
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2178
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2179
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2180
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2181
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2182
Calcium deposit in the skin
Calcinosis
2183
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2184
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2185
Skin thickening of the fingers
Sclerodactyly
2186
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2187
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2188
Two types of immunodeficiency
Primary | Secondary
2189
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2190
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2191
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2192
Differentiation of mature plasma cells which requires T cells
Class switching
2193
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2194
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2195
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2196
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2197
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2198
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2199
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2200
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2201
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2202
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2203
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2204
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2205
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2206
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2207
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2208
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2209
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2210
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2211
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2212
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2213
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2214
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2215
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2216
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2217
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2218
Promote survival and differentiation of B cells
BAFF
2219
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2220
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2221
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2222
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2223
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2224
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
2225
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
2226
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
2227
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
2228
Clinical manifestation of C2 deficiency
Associated with bacterial infections
2229
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
2230
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
2231
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
2232
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
2233
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
2234
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
2235
Two major target of HIV
Immune system and CNS
2236
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
2237
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
2238
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
2239
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
2240
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
2241
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
2242
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
2243
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
2244
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
2245
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
2246
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
2247
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
2248
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
2249
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
2250
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
2251
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
2252
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
2253
Group of diseases common of having deposition of amyloids
Amyloidosis
2254
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
2255
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
2256
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
2257
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
2258
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
2259
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
2260
Morphology of Amyloidosis in the heart
Subendocardial deposits
2261
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
2262
Protease that cleave and activate caspases
Granzyme
2263
End result of T-cell mediated cytotoxicity
Apoptosis
2264
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
2265
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
2266
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
2267
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
2268
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
2269
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
2270
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
2271
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
2272
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
2273
Cells involved in acute humoral rejection
B cells and Abs
2274
Type of rejection that occurs after months to years after transplantation
Chronic rejection
2275
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
2276
Clinical presentation of chronic rejection
Progressive organ dysfunction
2277
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
2278
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
2279
TH cell subset that recruits more macrophages mononuclear cells
TH1
2280
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
2281
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
2282
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
2283
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
2284
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
2285
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
2286
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
2287
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
2288
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
2289
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
2290
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
2291
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
2292
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
2293
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
2294
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
2295
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
2296
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
2297
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
2298
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
2299
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
2300
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
2301
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
2302
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
2303
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
2304
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
2305
Most common cause of death in SLE
Renal failure
2306
Second most common cause of death in SLE
Sepsis/infection
2307
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
2308
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
2309
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2310
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2311
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2312
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2313
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2314
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2315
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2316
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2317
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2318
Characteristic FANA pattern of SLE
Peripheral pattern
2319
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2320
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2321
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2322
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2323
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2324
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2325
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2326
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2327
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2328
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2329
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2330
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2331
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2332
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2333
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2334
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2335
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2336
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2337
Calcium deposit in the skin
Calcinosis
2338
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2339
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2340
Skin thickening of the fingers
Sclerodactyly
2341
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2342
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2343
Two types of immunodeficiency
Primary | Secondary
2344
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2345
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2346
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2347
Differentiation of mature plasma cells which requires T cells
Class switching
2348
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2349
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2350
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2351
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2352
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2353
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2354
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2355
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2356
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2357
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2358
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2359
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2360
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2361
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2362
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2363
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2364
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2365
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2366
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2367
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2368
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2369
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2370
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2371
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2372
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2373
Promote survival and differentiation of B cells
BAFF
2374
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2375
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2376
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2377
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2378
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2379
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
2380
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
2381
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
2382
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
2383
Clinical manifestation of C2 deficiency
Associated with bacterial infections
2384
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
2385
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
2386
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
2387
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
2388
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
2389
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
2390
Two major target of HIV
Immune system and CNS
2391
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
2392
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
2393
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
2394
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
2395
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
2396
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
2397
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
2398
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
2399
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
2400
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
2401
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
2402
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
2403
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
2404
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
2405
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
2406
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
2407
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
2408
Group of diseases common of having deposition of amyloids
Amyloidosis
2409
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
2410
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
2411
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
2412
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
2413
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
2414
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
2415
Morphology of Amyloidosis in the heart
Subendocardial deposits
2416
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
2417
Protease that cleave and activate caspases
Granzyme
2418
End result of T-cell mediated cytotoxicity
Apoptosis
2419
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
2420
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
2421
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
2422
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
2423
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
2424
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
2425
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
2426
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
2427
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
2428
Cells involved in acute humoral rejection
B cells and Abs
2429
Type of rejection that occurs after months to years after transplantation
Chronic rejection
2430
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
2431
Clinical presentation of chronic rejection
Progressive organ dysfunction
2432
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
2433
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
2434
TH cell subset that recruits more macrophages mononuclear cells
TH1
2435
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
2436
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
2437
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
2438
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
2439
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
2440
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
2441
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
2442
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
2443
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
2444
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
2445
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
2446
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
2447
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
2448
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
2449
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
2450
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
2451
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
2452
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
2453
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
2454
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
2455
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
2456
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
2457
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
2458
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
2459
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
2460
Most common cause of death in SLE
Renal failure
2461
Second most common cause of death in SLE
Sepsis/infection
2462
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
2463
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
2464
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2465
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2466
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2467
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2468
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2469
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2470
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2471
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2472
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2473
Characteristic FANA pattern of SLE
Peripheral pattern
2474
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2475
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2476
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2477
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2478
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2479
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2480
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2481
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2482
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2483
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2484
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2485
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2486
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2487
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2488
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2489
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2490
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2491
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2492
Calcium deposit in the skin
Calcinosis
2493
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2494
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2495
Skin thickening of the fingers
Sclerodactyly
2496
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2497
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2498
Two types of immunodeficiency
Primary | Secondary
2499
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2500
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2501
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2502
Differentiation of mature plasma cells which requires T cells
Class switching
2503
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2504
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2505
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2506
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2507
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2508
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2509
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2510
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2511
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2512
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2513
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2514
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2515
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2516
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2517
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2518
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2519
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2520
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2521
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2522
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2523
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2524
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2525
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2526
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2527
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2528
Promote survival and differentiation of B cells
BAFF
2529
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2530
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2531
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2532
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2533
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2534
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
2535
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
2536
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
2537
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
2538
Clinical manifestation of C2 deficiency
Associated with bacterial infections
2539
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
2540
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
2541
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
2542
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
2543
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
2544
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
2545
Two major target of HIV
Immune system and CNS
2546
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
2547
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
2548
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
2549
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
2550
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
2551
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
2552
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
2553
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
2554
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
2555
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
2556
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
2557
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
2558
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
2559
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
2560
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
2561
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
2562
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
2563
Group of diseases common of having deposition of amyloids
Amyloidosis
2564
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
2565
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
2566
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
2567
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
2568
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
2569
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
2570
Morphology of Amyloidosis in the heart
Subendocardial deposits
2571
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
2572
Protease that cleave and activate caspases
Granzyme
2573
End result of T-cell mediated cytotoxicity
Apoptosis
2574
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
2575
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
2576
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
2577
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
2578
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
2579
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
2580
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
2581
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
2582
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
2583
Cells involved in acute humoral rejection
B cells and Abs
2584
Type of rejection that occurs after months to years after transplantation
Chronic rejection
2585
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
2586
Clinical presentation of chronic rejection
Progressive organ dysfunction
2587
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
2588
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
2589
TH cell subset that recruits more macrophages mononuclear cells
TH1
2590
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
2591
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
2592
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
2593
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
2594
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
2595
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
2596
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
2597
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
2598
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
2599
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
2600
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
2601
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
2602
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
2603
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
2604
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
2605
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
2606
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
2607
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
2608
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
2609
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
2610
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
2611
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
2612
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
2613
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
2614
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
2615
Most common cause of death in SLE
Renal failure
2616
Second most common cause of death in SLE
Sepsis/infection
2617
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
2618
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
2619
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2620
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2621
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2622
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2623
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2624
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2625
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2626
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2627
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2628
Characteristic FANA pattern of SLE
Peripheral pattern
2629
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2630
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2631
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2632
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2633
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2634
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2635
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2636
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2637
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2638
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2639
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2640
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2641
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2642
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2643
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2644
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2645
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2646
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2647
Calcium deposit in the skin
Calcinosis
2648
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2649
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2650
Skin thickening of the fingers
Sclerodactyly
2651
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2652
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2653
Two types of immunodeficiency
Primary | Secondary
2654
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2655
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2656
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2657
Differentiation of mature plasma cells which requires T cells
Class switching
2658
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2659
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2660
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2661
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2662
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2663
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2664
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2665
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2666
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2667
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2668
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2669
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2670
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2671
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2672
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2673
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2674
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2675
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2676
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2677
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2678
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2679
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2680
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2681
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2682
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2683
Promote survival and differentiation of B cells
BAFF
2684
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2685
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2686
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2687
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2688
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2689
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
2690
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
2691
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
2692
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
2693
Clinical manifestation of C2 deficiency
Associated with bacterial infections
2694
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
2695
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
2696
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
2697
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
2698
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
2699
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
2700
Two major target of HIV
Immune system and CNS
2701
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
2702
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
2703
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
2704
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
2705
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
2706
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
2707
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
2708
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
2709
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
2710
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
2711
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
2712
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
2713
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
2714
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
2715
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
2716
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
2717
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
2718
Group of diseases common of having deposition of amyloids
Amyloidosis
2719
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
2720
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
2721
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
2722
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
2723
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
2724
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
2725
Morphology of Amyloidosis in the heart
Subendocardial deposits
2726
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
2727
Protease that cleave and activate caspases
Granzyme
2728
End result of T-cell mediated cytotoxicity
Apoptosis
2729
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
2730
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
2731
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
2732
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
2733
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
2734
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
2735
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
2736
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
2737
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
2738
Cells involved in acute humoral rejection
B cells and Abs
2739
Type of rejection that occurs after months to years after transplantation
Chronic rejection
2740
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
2741
Clinical presentation of chronic rejection
Progressive organ dysfunction
2742
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
2743
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
2744
TH cell subset that recruits more macrophages mononuclear cells
TH1
2745
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
2746
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
2747
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
2748
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
2749
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
2750
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
2751
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
2752
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
2753
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
2754
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
2755
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
2756
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
2757
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
2758
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
2759
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
2760
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
2761
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
2762
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
2763
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
2764
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
2765
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
2766
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
2767
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
2768
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
2769
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
2770
Most common cause of death in SLE
Renal failure
2771
Second most common cause of death in SLE
Sepsis/infection
2772
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
2773
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
2774
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2775
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2776
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2777
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2778
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2779
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2780
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2781
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2782
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2783
Characteristic FANA pattern of SLE
Peripheral pattern
2784
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2785
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2786
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2787
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2788
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2789
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2790
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2791
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2792
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2793
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2794
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2795
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2796
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2797
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2798
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2799
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2800
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2801
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2802
Calcium deposit in the skin
Calcinosis
2803
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2804
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2805
Skin thickening of the fingers
Sclerodactyly
2806
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2807
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2808
Two types of immunodeficiency
Primary | Secondary
2809
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2810
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2811
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2812
Differentiation of mature plasma cells which requires T cells
Class switching
2813
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2814
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2815
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2816
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2817
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2818
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2819
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2820
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2821
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2822
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2823
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2824
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2825
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2826
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2827
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2828
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2829
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2830
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2831
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2832
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2833
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2834
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2835
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2836
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2837
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2838
Promote survival and differentiation of B cells
BAFF
2839
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2840
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2841
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2842
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2843
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2844
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
2845
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
2846
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
2847
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
2848
Clinical manifestation of C2 deficiency
Associated with bacterial infections
2849
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
2850
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
2851
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
2852
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
2853
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
2854
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
2855
Two major target of HIV
Immune system and CNS
2856
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
2857
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
2858
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
2859
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
2860
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
2861
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
2862
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
2863
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
2864
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
2865
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
2866
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
2867
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
2868
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
2869
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
2870
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
2871
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
2872
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
2873
Group of diseases common of having deposition of amyloids
Amyloidosis
2874
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
2875
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
2876
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
2877
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
2878
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
2879
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
2880
Morphology of Amyloidosis in the heart
Subendocardial deposits
2881
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
2882
Protease that cleave and activate caspases
Granzyme
2883
End result of T-cell mediated cytotoxicity
Apoptosis
2884
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
2885
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
2886
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
2887
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
2888
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
2889
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
2890
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
2891
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
2892
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
2893
Cells involved in acute humoral rejection
B cells and Abs
2894
Type of rejection that occurs after months to years after transplantation
Chronic rejection
2895
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
2896
Clinical presentation of chronic rejection
Progressive organ dysfunction
2897
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
2898
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
2899
TH cell subset that recruits more macrophages mononuclear cells
TH1
2900
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
2901
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
2902
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
2903
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
2904
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
2905
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
2906
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
2907
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
2908
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
2909
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
2910
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
2911
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
2912
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
2913
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
2914
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
2915
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
2916
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
2917
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
2918
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
2919
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
2920
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
2921
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
2922
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
2923
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
2924
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
2925
Most common cause of death in SLE
Renal failure
2926
Second most common cause of death in SLE
Sepsis/infection
2927
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
2928
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
2929
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
2930
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
2931
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
2932
Non-erosive synovitis with little joint deformity in SLE
Arthritis
2933
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
2934
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
2935
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
2936
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
2937
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
2938
Characteristic FANA pattern of SLE
Peripheral pattern
2939
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
2940
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
2941
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
2942
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
2943
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
2944
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
2945
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
2946
Sjogren Syndrome in association with another autoimmune disease
Secondary form
2947
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
2948
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
2949
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
2950
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
2951
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
2952
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
2953
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
2954
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
2955
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
2956
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
2957
Calcium deposit in the skin
Calcinosis
2958
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
2959
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
2960
Skin thickening of the fingers
Sclerodactyly
2961
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
2962
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
2963
Two types of immunodeficiency
Primary | Secondary
2964
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
2965
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
2966
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
2967
Differentiation of mature plasma cells which requires T cells
Class switching
2968
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
2969
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
2970
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
2971
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
2972
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
2973
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
2974
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
2975
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
2976
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
2977
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
2978
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
2979
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
2980
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
2981
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
2982
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
2983
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
2984
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
2985
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
2986
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
2987
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
2988
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
2989
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
2990
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
2991
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
2992
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
2993
Promote survival and differentiation of B cells
BAFF
2994
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
2995
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
2996
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
2997
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
2998
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
2999
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
3000
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
3001
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
3002
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
3003
Clinical manifestation of C2 deficiency
Associated with bacterial infections
3004
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
3005
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
3006
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
3007
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
3008
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
3009
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
3010
Two major target of HIV
Immune system and CNS
3011
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
3012
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
3013
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
3014
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
3015
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
3016
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
3017
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
3018
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
3019
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
3020
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
3021
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
3022
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
3023
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
3024
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
3025
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
3026
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
3027
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
3028
Group of diseases common of having deposition of amyloids
Amyloidosis
3029
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
3030
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
3031
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
3032
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
3033
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
3034
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
3035
Morphology of Amyloidosis in the heart
Subendocardial deposits
3036
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
3037
Protease that cleave and activate caspases
Granzyme
3038
End result of T-cell mediated cytotoxicity
Apoptosis
3039
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
3040
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
3041
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
3042
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
3043
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
3044
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
3045
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
3046
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
3047
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
3048
Cells involved in acute humoral rejection
B cells and Abs
3049
Type of rejection that occurs after months to years after transplantation
Chronic rejection
3050
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
3051
Clinical presentation of chronic rejection
Progressive organ dysfunction
3052
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
3053
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
3054
TH cell subset that recruits more macrophages mononuclear cells
TH1
3055
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
3056
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
3057
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
3058
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
3059
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
3060
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
3061
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
3062
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
3063
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
3064
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
3065
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
3066
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
3067
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
3068
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
3069
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
3070
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
3071
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
3072
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
3073
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
3074
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
3075
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
3076
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
3077
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
3078
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
3079
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
3080
Most common cause of death in SLE
Renal failure
3081
Second most common cause of death in SLE
Sepsis/infection
3082
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
3083
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
3084
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
3085
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
3086
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
3087
Non-erosive synovitis with little joint deformity in SLE
Arthritis
3088
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
3089
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
3090
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
3091
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
3092
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
3093
Characteristic FANA pattern of SLE
Peripheral pattern
3094
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
3095
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
3096
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
3097
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
3098
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
3099
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
3100
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
3101
Sjogren Syndrome in association with another autoimmune disease
Secondary form
3102
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
3103
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
3104
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
3105
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
3106
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
3107
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
3108
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
3109
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
3110
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
3111
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
3112
Calcium deposit in the skin
Calcinosis
3113
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
3114
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
3115
Skin thickening of the fingers
Sclerodactyly
3116
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
3117
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
3118
Two types of immunodeficiency
Primary | Secondary
3119
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
3120
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
3121
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
3122
Differentiation of mature plasma cells which requires T cells
Class switching
3123
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
3124
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
3125
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
3126
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
3127
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
3128
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
3129
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
3130
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
3131
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
3132
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
3133
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
3134
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
3135
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
3136
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
3137
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
3138
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
3139
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
3140
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
3141
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
3142
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
3143
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
3144
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
3145
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
3146
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
3147
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
3148
Promote survival and differentiation of B cells
BAFF
3149
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
3150
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
3151
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
3152
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
3153
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
3154
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
3155
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
3156
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
3157
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
3158
Clinical manifestation of C2 deficiency
Associated with bacterial infections
3159
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
3160
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
3161
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
3162
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
3163
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
3164
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
3165
Two major target of HIV
Immune system and CNS
3166
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
3167
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
3168
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
3169
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
3170
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
3171
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
3172
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
3173
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
3174
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
3175
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
3176
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
3177
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
3178
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
3179
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
3180
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
3181
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
3182
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
3183
Group of diseases common of having deposition of amyloids
Amyloidosis
3184
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
3185
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
3186
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
3187
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
3188
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
3189
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
3190
Morphology of Amyloidosis in the heart
Subendocardial deposits
3191
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```
3192
Protease that cleave and activate caspases
Granzyme
3193
End result of T-cell mediated cytotoxicity
Apoptosis
3194
Three types of transplant rejection of kidney cells
1. Hyperacute rejection 2. Acute rejection 3. Chronic rejection
3195
Type of rejection that occurs minute or hours after transplantation due to pre-formed anti-donor Abs present in the circulation of the recipient
Hyperacute rejection
3196
Gross appearance of hyperacute rejection
Mottled, cyanotic, flaccid kidney | Pale, hyperemic areas with white infarct
3197
Two subtypes of acute rejection
Acute cellular rejection | Acute humoral rejection
3198
Type of rejection that occurs a few days after cessation of immunosuppressive therapy
Acute rejection
3199
Subtype of acute rejection that characterized by interstitial mononuclear infiltrate
Acute cellular rejection
3200
Subtype of acute rejection that is characterized by necrotizing vasculitis with endothelial cell necrosis causing extensive necrosis of renal parenchyma
Acute humoral rejection
3201
Cells involved in acute cellular rejection
CD4+ and cytotoxic T cells: damage tubular and vascular endothelial cells CD8+ T cells: recruits cytokines causing inflammation that damages the graft, finally resulting to vascular cleavage
3202
Manifestations of acute rejection
Damage to glomeruli and blood vessels Inflammation of glomeruli and peritubular capillaries Deposition of complement products
3203
Cells involved in acute humoral rejection
B cells and Abs
3204
Type of rejection that occurs after months to years after transplantation
Chronic rejection
3205
Morphology of chronic rejection
Vascular changes: Obliterative intimal fibrosis Interstitial fibrosis Tubular atrophy with loss of renal parenchyma
3206
Clinical presentation of chronic rejection
Progressive organ dysfunction
3207
Cytokines that differentiate CD4+ T cells into TH1
IL-12, IFN-gamma
3208
Cytokines that differentiate CD4+ T cells into TH17
IL-1, IL-16 and IL-23
3209
TH cell subset that recruits more macrophages mononuclear cells
TH1
3210
TH cell subset that recruits neutrophils and monocytes creating a more neutrophilic appearance
TH17
3211
Prototype disorders of Type I: Immediate hypersensitivity reactions
Anaphylaxis; allergies, bronchial asthma (atopic forms)
3212
Prototype disorders of Type II: Ab-mediated hypersensitivity
AIHA (IIa) Goodpasture syndrome (IIb) Graves, Myasthenia Gravis (IIc)
3213
Prototype disorders of Type III: Immune-complex mediated hypersensitivity
SLE Some forms of Glomerulonephritis Serum sickness Arthus reaction
3214
Prototype disorders of Type IV: Cell-mediated hypersensitivity
Tuberculosis (IVa) Response to viral infections (IVb) Transplant rejection
3215
Disease examples of cell-mediated hypersensitivity reactions
``` Rheumatoid arthritis Multiple sclerosis DM type I Inflammatory bowel disease Psoriasis Contact sensitivity ```
3216
Rheumatoid arthritis Target Ag: ____________ Manifestation: _____________
Target Ag: Collagen and citrullinated self proteins | Manifestation: Chronic arthritis with inflammation, destruction of articular cartilage
3217
Multiple sclerosis Target Ag: ____________ Manifestation: _____________
Target Ag: Protein Ag in myelin | Manifestation: Demyelination in CNS with perivascular inflammation; paralysis
3218
DM type I Target Ag: ____________ Manifestation: _____________
Target Ag: Ag of pancreatic islets of B cells (insulin, glutamic acid decaraboxylase, etc) Manifestation: Insulitis (chronic inflammation in islets), destruction of active cells; diabetes
3219
Inflammatory bowel disease Target Ag: ____________ Manifestation: _____________
Target Ag: Enteric disease; bacteria; self Ag | Manifestation: Chronic intestinal inflammation or obstruction
3220
Psoriasis Target Ag: ____________ Manifestation: _____________
Target Ag: Unknown | Manifestation: Destructive plaques on the skin
3221
Contact sensitivity Target Ag: ____________ Manifestation: _____________
Target Ag: Various environment chemicals (e.g. urushiol from poison ivy or oak); Therapeutic drugs Manifestation: Epidermal necrosis, dermal inflammation skin rash and blisters
3222
These result from tissue injury cause by T cells or Abs that react against self-antigens
Autoimmune diseases
3223
Features of autoimmune diseases in general
1. Female predilection 2. Characterized by remissions and exacerbations 3. Increased incidence of malignancy 4. Familial prevalence of the same or other A.I.D. 5. Clinical and serologic overlaps 6. Patients often have increase immunoglobulin in the serum
3224
Autoimmune disease may arise from combination of
1. Inheritance of susceptibility genes which contribute to breakdown of self-tolerance 2. Environmental triggers like infections and tissue damage which mimics endogenous proteins 3. Promotion of the activation of self-reactive lymphocytes
3225
Organ specific spectrum of autoimmune diseases
Ab directed against a single organ/tissue | Localized lesions
3226
Examples of organ specific spectrum of autoimmune diseases
``` Hasimoto’s thyroiditis Pernicios anemia Thyrotoxicosis (Graves’ disease) Autoimmune hemolytic anemia (AIHA) Immune thromocytopenic purpura (ITP) Insulin-dependent diabetes mellitus (IDDM) ```
3227
Non-organ specific spectrum of autoimmune diseases
Ab not directed to a single organ/tissue | Widespread lesions
3228
Example of organ specific spectrum of autoimmune diseases
``` SLE Sjorgren syndrome Scleroderma Rheumatoid arthritis Inflammatory myopathies Mixed connective tissue disease ```
3229
Rare autoimmune in which which the antibodies attack the basement membrane of the glomerulus and alveoli causing pulmonary haemorrhage and kidney failure
Goodpasture syndrome
3230
Chronic, repeating relapsing illness characterized by injury to the skin, joints, kidney and basement membrane (areas with high blood flow)
SLE
3231
Affects multiple organs due to a wast array of autoAbs, particularly anti-nucleus Abs
SLE
3232
Clinical feature of SLE
1. More common in females (10:1 - 20:1) | 2. 2nd-3rd decade: acute, more omninous; Older: more insidious, better prognosis
3233
Most common signs and symptoms of SLE
1. Hematologic - 100% 2. Musculo-skeletal (arthritis) - 90% 3. Skin (Butterfly rash) - 85% 4. Fever - 83% (55-85%) 5. Renal, pulmonary, cardiac - 30-50%
3234
Course of SLE
Acute: death within weeks to months Chronic: with treatment, 10-20 years
3235
Most common cause of death in SLE
Renal failure
3236
Second most common cause of death in SLE
Sepsis/infection
3237
Some factors related to pathogenesis of SLE
1. Genetic: IgA, C2 deficiency; greater chance in family groups associated with certain halotypes (most common) 2. Environmental: drugs, UV light, hormones (stimulate formation of Abs against DNA) 3. Immunologic: defective elimination of self-reactive B cells in the bone marrow, CD4+ T cells specific for nucleosomal Ag escape tolerance
3238
Classification scheme in diagnosing SLE
1. Patients has four or more clinical and immunologic criteria present (with at least one clinical and one immunologic) 2. Demonstrate presence of Ab to Anti-DNA (more specific)
3239
Three mechanisms of tissue damage in SLE
1. Immune complex disease (Type III) 2. Ab directed against cell type (Type II) 3. Presence of Antiphospholipid Antibodies (Secondary to APAS)
3240
Mechanism of immune complex disease in SLE
Ab against DNA Ab to histones Ab to nonhistone proteins bound to RNA Ab to nuclear Ag
3241
Clinical manifestation of immune complex disease in SLE
1. Vasculitis 2. Glomerulonephritis 3. Arthritis 4. Heart 5. Skin 6. Others: Interstitial pneumonitis, cerebral infarcts and hemorrhages, pericariditis
3242
Non-erosive synovitis with little joint deformity in SLE
Arthritis
3243
Affects small arteries and arterioles (in spleen: onion-skin lesions) in SLE
Vasculitis
3244
Endocarditis in SLE characterized by 1-3mm warty deposits on any valve, also called vegetative
Liebmann-Sacks endocarditis
3245
A sign of SLE seen histologically as H&E: liquefactive degeneration of basal layer of epidermis and edema at the D-E junction IF: Ig and complement deposits in D-E junction
Malar rash
3246
Mechanism of Ab mediated disease
Ab against RBCs (anemia) Ab against WBC (leukopenia) Ab against platelets (thrombocytopenia)
3247
Patterns of FANA
1. Homogenous (anti-DNA protein) 2. Peripheral (anti-nucleolar DNA) 3. Nucleolar (anti-nucleolar RNA) 4. Speckled (anti-ENA)
3248
Characteristic FANA pattern of SLE
Peripheral pattern
3249
``` Present in 40-50% of SLE patients Bind to cardiolipin Ag which is used in syphilis testing (false positive) Predisposed thrombosis (venous and arterial; deep vein thrombosis) ```
Anti-phospholipid Ab
3250
Neutrophil or macrophage that has phagocytosed the denature nuclear material or Ab-coated nucleus of another cell
LE cell
3251
Typical features of SLE
1. History and PE: young female with malar rash, fever, joint pains, hematologic problem 2. (+) ANA: peripheral pattern 3. Ab to dsDNA and Smith Ag 4. (+) Lupus band test on skin biopsy 5. Decrease complement level: C3 6. Renal biopsy shows glomerulonephritis and immune complex deposits by immunoflourescence
3252
Chronic inflammatory disease characterized by dry eyes and dry mouth resulting from immunologically mediated destruction of the lacrimal and salivary glands
Sjogren Syndrome
3253
Primary form or isolated disorder of Sjorgen syndrome
Sicca Syndrome
3254
Most common autoimmune disease associated with another autoimmune diseases
Rheumatoid arthritis (75% have rheumatoid factor)
3255
90% have Abs directed to ribonucleoprotein antigens SS-A (Ro) and SS-B (LA)
Secondary form
3256
Sjogren Syndrome in association with another autoimmune disease
Secondary form
3257
Dry eyes that causes blurring of vision, burning and itching, thick secretions in the conjunctival sac
Keratoconjunctivitis
3258
Difficulty in swallowing, decreased ability to taste, cracks and fissures in the mouth, dryness of buccal mucosa
Xerostomia
3259
Clinical feature of Sjogren syndrome
1. Most common in 50-60 year old women 2. Keratoconjunctivitis 3. Xerostomia 4. Others: parotid gland enlargement (50%), dryness of the nasal mucosa, epistaxis, recurrent bronchitis and pneumonitis 5. Increased risk of developing lymphoid malignancies 6. Extraglandular disease in 1/3 of patients manifested as synovitis, diffuse pulmonary fibrosis and peripheral neuropathy
3260
Most common type lymphoid malignancy in Sjogren syndrome
Marginal Zone lymphoma
3261
Abnormal accumulation of fibrous tissue in the skin and multiple organs
Systemic sclerosis (Scleroderma)
3262
Characterized by progressive fibrosis in multiple tissues, obliterate vascular disease and evidence of autoimmunity, mainly the production of multiple autoantibodies
Scleroderma
3263
Two major categories of Scleroderma
Diffuse scleroderma | Limited scleroderma
3264
Widespread involvement at onset with rapid progression and early visceral involvement (GIT and lungs)
Diffuse scleroderma
3265
Skin involvement confined to fingers, forearm and face with late visceral involvement
Limited scleroderma
3266
Symptoms of limited type scleroderma
``` CREST syndrome C-alcinosis R-aynaud phenomenon E-sophageal dysmotility S-clerodactyly T-elangiectasia ```
3267
Calcium deposit in the skin
Calcinosis
3268
Exaggerated type of vasocontriction in the hands with the fingers undergoing characteristic pallor and hypereremia when exposed to cold
Raynaud phenomenon
3269
Difficulty in swallowing because of fibrosis and sclerosis of the esophagus due to chronic inflammation
Esophageal dymotility
3270
Skin thickening of the fingers
Sclerodactyly
3271
Dilatation of capillaries of the hands, face and mucous membrane presenting a spider-like appearance (spider veins)
Telangiectasia
3272
Suppressed immune system which may be caused by inherited defects affecting the immune system development or secondary to other diseases
Immunodeficiency
3273
Two types of immunodeficiency
Primary | Secondary
3274
Type of immunodeficiency which is almost always genetically determined, usually X-linked, seen in infancy (6 months-2 years) and associated with recurrent infections
Primary immunodeficiency
3275
Acquired type of immunodeficiency which result from altered immune function caused by malnutrition, viral infection, irradiation, use of immunosuppressive drugs, lymphoproliferative diseases
Secondary immunodeficiency
3276
Most common causes of secondary immunodeficiency
Chemotherapy and radiotherapy
3277
Differentiation of mature plasma cells which requires T cells
Class switching
3278
Primary immunodeficiency is based on deficient components of the immune system
1. Stem cell deficiency 2. B-cells deficiency 3. T-cell deficiency 4. Deficiency of myeloid elements 5. Complement deficiency
3279
Example of primary type diseases
B-cell deficiency: Bruton’s X-linked Agammaglobulinemia T-cell deficiency: DiGeorge syndrome Stem cell defect: Sever Combines Immunodeficiency (SCID) Complement deficiency Others: CVID, Hyper IgM syndrome, Wiscott-Alrich Syndrome, X-linked Lymphoproliferative disorder, Isolated IgA deficiency
3280
``` B-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: Normal Susceptibility to infections: Pyogenic bacteria (Staphylococcus, Pneumococcus, etc) Treatment: Gamma-globulin
3281
Abnormality in projection of the BTK gene (Bruton tyrosine kinase) which is responsible for sending maturation signals from the pre-B-cells and B cell receptors
Bruton’s X-linked agammaglobulinemia
3282
Failure of B cell maturation and absence of gammaglobulins
Bruton’s X-linked agammaglobulinemia
3283
Pathologic finding of B-cell deficiency
B-cells almost absent in lymphocytes, spleen, bone marrow and connective tissues Germinal centers in the lymph nodes, Peyer’s patches, appendix and tonsils are underdeveloped
3284
Features of Bruton’s X-linked agammaglobulinemia
Lack of mature B cells in the circulation Serum levels of all Igs are depressed T cell numbers and function are normal
3285
``` T-cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: Intracellular microbes (Virus, Fungi, TB) Treatment: Thymus graft
3286
Pathologic findings of T-cell deficiency
Low circulating T-lymphocytes Depleted T-dependent paracortical ares of the lymph node and T-dependent areas of the spleen Plasma cells are normal in number in lymphoid tissues
3287
Failure of the development of the 3rd and 4th pharyngeal pouches
Di George Syndrome
3288
Features of DiGeorge Syndrome
Thymic hypoplasia or aplasia: T cell deficiency Parathyroid hypoplasia: Tetany Congenital defects of the heart and great vessels (due to deletion of gene that maps Ch22q11) Dysmorphic fascies
3289
``` Stem cell deficiency Humoral response: ________________ Cell-mediated response: ____________ Susceptibility to infections: ____________ Treatment: ____________ ```
Humoral response: ⬇️⬇️ Cell-mediated response: ⬇️⬇️ Susceptibility to infections: All types Treatment: Bone marrow graft
3290
Pathologic findings of stem cell deficiency
Absence of T and B cells in the blood, lymph nodes and spleen Thymus devoid of lymphoid cells or Hassall’s corpuscles
3291
Two types of SCID
X-linked SCID | Adenosine Deaminase deficiency
3292
Type of SCID that is found in 50-60% of cases caused by mutations of common gamma chain of the subunit of the cytokine receptor
X-linked SCID
3293
Clinical manifestations of X-linked SCID
Pro-T cells cannot differentiate into immature T-cells Normal number of B-cells but inability to produce Ig due to inhibited class-switching Thymus contains lobules of undifferentiated epithelial cells that resembles fetal cells
3294
Autosomal recessive type of SCID
Adenosine Deaminase deficiency
3295
This enzyme reduces the synthesis of deoxyadenosine and its derivatives which are toxic to rapidly dividing cells
ADA deficiency
3296
Clinical manifestations of ADA deficiency
Susceptible to all types of infections Absence of T and B cells in the blood, lymph nodes and spleen (humoral and cellular immunity are affected) Mature looking but small thymus with remnants of Hassal’s corpuscles
3297
Symptoms of ADA deficiency
Oral thrush Extensive diaper rash at birth Failure to thrive
3298
DiGeorge syndrome vs. SCID
DiGeorge syndrome: Failure of immature T cells to develop into mature ones SCID: failure of pro-T cells to develop into immature ones (block is at an earlier phase of development)
3299
Bruton’s X-linked agammaglobulinemia vs. CVID
Bruton’s X-linked agammaglobulinemia: almost no B cell proliferation ➡️ agammaglobulinemia ➡️ B cell containing areas in the lymph nodes are hypoplastic CVID: B cell proliferation with out differentiation into plasma cells ➡️ no feedback inhibition of B cell proliferation rendered by Igs ➡️ B cell containing areas in the lymph nodes are hyperplastic; later onset
3300
Common Variable Immunodeficiency (CVID) Pathology: ____________ Features: ______________
Pathology: abnormality in cytokine BAFF receptor Features: affects both sexes, hypogammaglobulinemia, impaired Ab response to infection or vaccination, increase susceptibility to infections
3301
Hyper IgM syndrome Pathology: ____________ Features: ______________
Pathology: failure in class-switchig due to mutation on gene encoding for CD40L Features: Absent IgA and IgE, very low IgG, susceptible to recurrent pyogenic infections, 70% X-linked, 30% autosomal recessive
3302
Wiscott-Aldrich syndrome Pathology: ____________ Features: ______________ Treatment: ____________
Pathology: X-linked recessive disease, mutations ion gene encoding for WASP on Xp11.23 Features: unable to produce Ab against polysaccharide Ag and poor response against protein Ag, susceptible to infection with encapsulated pyogenic bacteria, low serum IgM with normal IgG and IgA but increased IgE Treatment: Bone marrow transplantation
3303
Promote survival and differentiation of B cells
BAFF
3304
Believed to link membrane receptors to cytoskeletal elements and is involved in cytoskeleton dependent responses such as migration and signal transduction
WASP
3305
X-linked lymphoproliferative disorder Pathology: ____________ Features: ______________
Pathology: Inability to eliminates Epstein-barr virus (EBV) causing infectious mononucleosis and development of B-cell tumors Features: Inability to form germinal centers, produce high affinity abnormalities (Ab unable of attacking viruses), not susceptible to other viral infections besides EBV, 80% due to mutation in SAP leading to attenuated NK and T cell activation and susceptibility to viral infections
3306
Isolated IgA deficiency Pathology: ____________ Features: ______________
Pathology: Low levels of both serum and secretory IgA due to impaired differentiation of B cells Features: Familial or acquired (measles or toxoplasmosis), sever anaphylactic secretion to transfusion of IgA containing blood because IgA is recognized as foreign, lack of IgA, asymptomptomatic but secretory defenses are weakened, susceptibility to respiratory, GIT and congenital infections
3307
Most common form of primary immunoglobulin deficiency
Isolated IgA deficiency
3308
Major Ig in mucosal secretions involved in defending the airways and GIT
IgA
3309
Clinical feature of complement deficiency
Associated with increase susceptibility to bacterial infections (C3 deficiency) High incidence of CT diseases (C2 and C4 deficiency with SLE)
3310
Common complement deficiencies
C1 inhibitor C2 C2 C5-9
3311
Clinical manifestation of C1 inhibitor deficiency
Angioneurotic edema
3312
Clinical manifestation of C2 deficiency
Associated with CT diseases in SLE
3313
Clinical manifestation of C2 deficiency
Associated with bacterial infections
3314
Clinical manifestation of C5-9 deficiency
Associated with repeated Neisseria infections and increased risk for meningitis and gonorrhea
3315
Prototype of secondary type diseases
Acquired Immunodeficiency Syndrome (AIDS)
3316
Etiology of AIDS
HIV1 - U.S. Central Africa, Europe, Asia - inferred origin: Common chimpanzees - global prevalende - mutated from simian immunodeficiency HIV2 - West Africa - less virulence, less infectivity - inferred origin: Sooty mangabey
3317
Risk group for HIV
``` Homosexuals or bisexual males IV users (25% chance) Hemophiliacs Blood transfusion recipients (90% chance) Heterosexual contacts ```
3318
Transmission of HIV
``` Sexual contact (Dominant mode of infection) Parenteral (IV drug needle, blood transfusion) Vertical transmission (25% chance) ```
3319
Route of vertical transmission
In utero via placental spread During delivery via child birth After birth via breastmilk
3320
Two major target of HIV
Immune system and CNS
3321
Immunologic alterations of HIV
Loss of CD4+ T cells (Dendritic cells and macrophages are infected) Abnormalities of B-cell function
3322
True or False. | Receptive intercourse causes an individual to be more predisposed to HIV infection than insertive.
True. 0.04-3% receptive anal intercourse 0.03% insertive anal intercourse 0.05-0.20% receptive penile-vaginal intercourse 0.01-0.35% insertive penile-vaginal intercourse 0-0.04% receptive oral intercourse 0-0.005% insertive oral intercourse
3323
Modes of destruction of CD4+ T cells during HIV infections
Directly destroyed by virus Subjected to apoptosis Killed by cytotoxic T lymphocytes
3324
Phases of HIV infection
Acute retroviral syndrome Middle chronic phase Final or crisis phase
3325
2-4 weeks self-limited, acute flu-like illness | 3-7 weeks post exposure, serum conversion of the virus
Acute retroviral phase
3326
Asymptomatic or generalized lymphadenopathy | Continued viral replication
Middle chronic phase
3327
Full blow AIDS Presence of opportunistic infections Lasting 7-10 years without chronic treatment
Final or crisis phase
3328
Stage of HIV infection where patient is asymptomatic with acute retroviral syndrome
Primary HIV infection
3329
Stage of HIV infection where patients are asymptomatic, CD4+ T cells >500 uL and persistent generalized lymphadenopathy
Clinical Stage 1
3330
Stage of HIV infection where minor mucocutaneous manifestation in the URT are present with CD4+ T cells <500 uL
Clinical stage 2
3331
Stage of HIV infection where weight loss, chronic diarrhea, persistent fever, oral candidiasis and other symptoms are more pronounced
Clinical Stage 3
3332
Stage of HIV infection considered as full blown AIDS with the presence of indicator diseases such as Pneumocystis jirovecii pneumonia, Kaposi’s sarcoma (HIV8), candidiasis, and other opportunistic infection
Clinical Stage 4
3333
Clinical features of AIDS
Young homosexual or IV drug abuser, positive HIV Ab test Early and middle phase: Acute symptoms or generalized lymphadenopathy Late: Fever, weight losee, generalized lymphadenopathy, Pneumocytosis carinii, Kaposi’s sarcoma, lymphoma, neurologic disease
3334
Morphology of AIDS
Non-specific Widespread opportunistic infection Malignant neoplasms: Kaposi’s sarcoma, B-cell lymphomas, primary lymphoma of the brain, invasice cancer of the uterine cervic Neurologic: aseptic meningitis, peripheral neuropathy, progressive encephalopathy (AIDS-dementia complex) Lymph nodes: Non-Hodgkin’s lymphoma Early: follicular hyperplasia (B-cell activation) Late: follicular involution and generalized lymphocytic depletion
3335
Prognosis of AIDS
Dismal: Most progress to AIDS in 10 years of infection No definitive treatment yet, only anti-retroviral therapy that contain HIV and maintain CD4+ T cell counts Without treatment, a patient with AIDS will die in 1 year
3336
Other causes of secondary immunodeficiency
Cancer chemotherapy Involvement of bone marrow in metastasis Protein-calorie malnutrition (Folate deficiency) Removal of the spleen
3337
Pathogenic fibrillar or misfolded proteins that accumulate within the tissues and organs
Amyloids
3338
Group of diseases common of having deposition of amyloids
Amyloidosis
3339
Aggregate into insoluble, cross-beta-pleated sheet tertiary conformation which will be deposited extracellularly causing pressure atrophy to adjacent parenchyma
Amyloidosis
3340
Fibrillar deposits bind to _________
Proteoglycans Glycosaminoglycans (heparan sulfate and dermatan sulfate) Plasma proteins
3341
Diagnosis of Amyloidosis
``` Biopsy and characteristic congo red stain Polarizing microscope (amyloid appears apple green birefringence) ```
3342
Morphology of Amyloidosis in the kidney
Enlarged, pale gray, waxy | Chronic vascular occlusion ➡️ shrunken protracted organ in advance disease
3343
Morphology of Amyloidosis in the spleen
Unapparent grossly Sago spleen: tapioca like granules within splenic follicles Lardaceous spleen: due to deposition in red pulp causing fusion of the deposits forming large geographic areas of amyloid
3344
Morphology of Amyloidosis in the liver
Unapparent grossly Hepatomegaly Deposits in space of Dissse which cause pressure atrophy leading to hepatic replacement
3345
Morphology of Amyloidosis in the heart
Subendocardial deposits
3346
Clinical manifestation of Amyloidosis
``` Non-specific Renal involvement Cardiac amyloidosis GI amyloidosis Vascular amyloidosis ```

Pathology (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions