Chapter 6 Flashcards
1
Q
Component cell of innate immunity found in epithelia, lymphoid organs, and most tissues; captures protein Ags and displays peptides for recognition by T cells as well as stimulates secretion of cytokines
A
Dendritic cells
2
Q
Component cell of innate immunity that functions in early protection against many viruses and intracellular bacteria
A
Natural killer cells
3
Q
Component cells of innate immunity that look like lymphocytes but have features of innate immunity
A
Innate lymphoid cells
[lack TCRs but produce cytokines similar to T cells; function in early defense against infections, recognize and eliminate stressed cells, provide cytokines that influence differentiation of T cells]
4
Q
Types of plasma proteins and their functions in innate immunity
A
Complement system - proteins that are activated by microbes using alternative and lectin pathways
Mannose-binding lectin and C-reactive protein - coat microbes and promote phagocytosis
Lung surfactant - provides protection against inhaled microbes
5
Q
3 possible cellular locations for PRRs
A
PM receptors detect extracellular microbes (TLRs, MBLs)
Endosomal receptors detect ingested microbes (TLRs)
Cytosolic receptor detect microbes in cytoplasm (NLRs, RIG-like receptors)
6
Q
Receptor type that recognizes a distinct type of microbial molecule before signaling a common pathway that leads to activation of transcription factors such as NF-kB and Interferon regulatory factors (IRFs)
A
Toll-like receptors (TLRs)
7
Q
Function of NF-kB and IRFs activated by TLR binding
A
NF-kB - stimulates synthesis and secretion of cytokines and the expression of adhesion molecules critical for the recruitment and activation of leukocytes
Interferon Regulatory Factors (IRFs) - stimuates production of antiviral cytokines (type I interferons)
8
Q
Cytosolic receptors that recognize a wide variety of substances and typically signal via the inflammasome
A
NLRs
9
Q
What types of substances are recognized by NLRs?
A
Products of necrotic cells (e.g., uric acid and released ATP)
Ion disturbances (e.g., loss of K+)
Some microbial products
10
Q
Result of gain-of-function mutaton in an NLR
A
Periodic fever syndrome, called autoinflammatory syndrome (can be treated with IL-1 antagonists)
[NLR may also play a role in gout, obesity-associated type 2 DM, atherosclerosis, etc.]
11
Q
Activation of NLRP-3 signals via the inflammasome to activate caspase-1, which cleaves _____ to _______, which is secreted leading to acute inflammation and fever
A
Pro-IL-1B; IL-1B
12
Q
Receptors found in the PM of macrophages and dendritic cells; function in detection of fungal glycans and elicit inflammatory reactions
A
C-type lectin receptors
13
Q
Receptor type found in cytosol of most cell types; detects nucleic acids of viruses and stimulates production of antiviral cytokines
A
RIG-like receptors
14
Q
Receptor type found on neutrophils, macrophages, and most leukocytes; recognizes bacterial peptides containing N-formylmethionyl
A
GPCRs
15
Q
Receptor type responsible for recognizing microbial sugars leading to phagocytosis of the microbe
A
Mannose receptors
16
Q
______ lymphocytes are those that have not yet encountered the Ag for which they are specific. Once they are activated by recognition of Ags, they either become _____ cells that eliminate microbes, or _____ cells that can react rapidly and strongly to that Ag in future encounters
A
Naive; effector; memory
17
Q
Lymphocytes can respond to multiple Ags, but once exposed to one, a lymphocyte will undergo ____ _____
A
Clonal selection (all lymph with same specificity are clones)
18
Q
Primary mechanism of developing lymphocyte diversity (when does it occur? What enzymes?)
A
Somatic recombination of the genes that encode the receptor proteins
Occurs during lymphocyte maturation (in thymus for Ts, in bone marrow for Bs)
Mediated by enzymes RAG-1 and RAG-2
19
Q
Result of inherited defects in RAG-1 and RAG-2
A
Failure to generate mature lymphocytes
20
Q
The majority of lymphocytes in blood and tissue are T lymphocytes. These recognize specific cell-bound Ag via a specific TCR. 95% of TCRs are heterodimers made up of an ___ and ____ polypeptide chain
These receptors recognize Ags presented by _____ molecules on the surfaces of APCs, a restriction which ensures T cells only see cell-associated Ags
A
Alpha; beta
MHC
21
Q
A small population of mature T cells are gamma-delta T cells. What do these recognize and where are they found?
A
Recognizes peptides, lipids, and small molecules, without assistance from MHC proteins
They aggregate at epithelial surfaces (e.g., skin, GI, urogenital tracts)
22
Q
A small subset of NK-T cells express a very limited diversity of TCRs. They recognize _______ that are displayed by the MHC-like molecule _______
A
Glycolipids; CD1
23
Q
Signal 1 consists of CD4+ T cell binding class II MHC of APC via alpha and beta chain of the TCR. What interaction provides signal 2?
A
CD28 on T cell binds CD80/CD86 on APC
24
Q
B cells recognize Ag via the B cell Ag receptor complex
Membrane-bound Abs of the ____ and ___ isotypes are present on the surface of all mature naive B cells. After stimulation by Ag they develop into ___ cells
A
IgM; IgD; plasma
25
Besides BCR, what are 2 other molecules essential for signaling B lymphocytes?
Type 2 complement receptor (CR2, or CD21)
CD40 - receives signals from helper T cells
26
The type 2 complement receptor (CR2, or CD21) that is essential for BCR signaling is also used in what pathologic mechanism?
CR2 is used by EBV to enter and infect B cells
27
What are langerhans cells
Dendritic cells located in the skin
28
Location and function of follicular dendritic cells
Located in germinal centers of lymphoid follicles in the spleen and lymph nodes
Trap Ags bound to Abs or complement proteins
Present Ags to B cells and select the highest affinity B cells
29
____ cells can activate macrophages and enhance their ability to kill ingested microbes
Macrophages phagocytose and destroy microbes that are opsonized by ___ or _____
T
IgG; C3b
30
Primary function is to destroy irreversibly stressed and abnormal cells, and do so without prior exposure to or activation by these cells
NK cells
31
Surface molecules of NK cells
CD16 — an Fc receptor for IgG (lyse IgG-coated target cells in ADCC)
CD56 - function unknown
32
NK cells are regulated by a balance between activating and inhibitory receptors and by many cytokines
___ and ___ stimulate proliferation
___ activates killing and secretion of _____, which serves to activate macrophages to destroy ingested microbes
IL-2; IL-15
IL-12; IFN-y
33
A virally infected cell will no longer be expressing ______ which is considered an inhibitory receptor for NK cells. Thus when the cell is not virally infected, the inhibitory receptor is engaged and the cell is not killed
Class I MHC
34
Genes that encode HLA molecules are clustered on chromosome _____; they are highly polymorphic with thousands of alleles of MHC genes
6
35
Where are MHC class I expressed and what are the types, what type of peptides do they display?
Expressed on all nucleated cells and platelets
HLA-A
HLA-B
HLA-C
Display peptides derived from proteins located in the cytoplasm (e.g., viral and tumor Ags)
36
Where are MHC class II expressed, where are they encoded, and what do they display
Mainly expressed on macrophages, B cells, and dendritic cells
Encoded by HLA-D:
HLA-DP
HLA-DQ
HLA-DR
Display Ags that are internalized into vesicles; typically from extracellular microbes and soluble proteins
37
How are HLA molecules inherited?
Individuals inherit one set of HLA genes from each parent
Typically 2 different molecules for every locus
38
Cytokines associated with innate immune responses
Produced by macrophages, dendritic cells, NK cells, etc.
Induce inflammation and inhibit viral replication
TNF, IL-1, IL-12, Type I IFNs, IFN-y, and chemokines
39
Cytokines role in adaptive immune responses
Produced mainly by CD4+ T cells
Promote lymphocyte proliferation and differentiation and to activate effector cells
IL-2, IL-4, IL-5, IL-17, and IFN-y
40
Role of cytokines in hematopoiesis
Stimulate hematopoeisis via colony-stimulating factors — role is to increase leukocyte numbers
GM-CSF; IL-7
41
The ______ serves the same role in immune responses to ______ Ags as lymph nodes do in response to lymph-borne Ags. Blood entering this organ flows through a network of ______ where Ags are trapped by _____ and _____
Spleen; bloodborne; sinusoids; DCs; macrophages
42
Major cytokines produced; immunological reactions triggered; host defense against; and role in disease of Th1 CD4+ cells
Cytokines: IFN-y
Reactions: macrophage activation, stimulation of IgG production
Host defense against IC microbes
Role in autoimmune and other chronic inflammatory diseases like IBD, psoriasis, and granulomatous inflammation
43
Major cytokines produced; immunological reactions triggered; host defense against; and role in disease of Th2 CD4+ cells
Cytokines: IL-4, IL-5, IL-13
Reactions: stimulation of IgE production; activation of mast cells and eosinophils
Host defense against helminthic parasites
Role in allergies
44
Major cytokines produced; immunological reactions triggered; host defense against; and role in disease of Th17 CD4+ cells
Cytokines: IL-17; IL-22
Reactions: recruitment of neutrophils, monocytes
Host defense against EC bacteria; fungi
Role in autoimmune and other chronic diseases like IBD, psoriasis, MS
45
Functions of Abs
Neutralization of microbe and toxins
Opsonization and phagocytosis
ADCC
Complement activation leading to lysis of microbes, phagocytosis of opsonized microbes, and inflammation
46
Immune mechanism of type I hypersensitivity
[immediate hypersensitivity]
Production of IgE —> immediate release of vasoactive amines and other mediators from mast cells; later recruitment of inflammatory cells
47
Histopathologic lesions associated with type I hypersensitivities
```
Vascular dilation
Edema
Smooth muscle contraction
Mucus production
Tissue injury
Inflammation
```
48
Prototypical disorders associated with type I hypersensitivities
Anaphylaxis
Allergies
Bronchial asthma (atopic forms)
49
Immune mechanism associated with type II hypersensitivities
[Ab-mediated hypersensitivity]
Production of IgG, IgM —> binds to Ag on target cell or tissue —> phagocytosis or lysis of target cell by activated complement or Fc receptors; recruitment of leukocytes
50
Histopathologic lesions associated with type II hypersensitivities
Phagocytosis and lysis of cells; in some diseases, funcntional derangements without cell or tissue injury
51
Prototypical disorders associated with type II hypersensitivities
Autoimmune hemolytic anemia
Goodpasture syndrome
[also autoimmune thrombocytopenic purpura, pemphigus vulgaris, vasculitis caused by ANCA, acute rheumatic fever, myasthenia gravis, graves disease, insulin-resistant diabetes, pernicious anemia]
52
Immune mechanisms associated with type III hypersensitivities
[immune complex-mediated]
Deposition of Ag-Ab complexes —> complement activation —> recruitment of leukocytes by complement products and Fc receptors —> release of enzymes and other toxic molecules
53
Histopathologic lesions associated with type III hypersensitivity
```
Inflammation
Necrotizing vasculitis (fibrinoid necrosis)
```
54
Prototypical disorders associated with type III hypersensitivities
SLE
Poststreptococcal glomerulonephritis
Serum sickness
Arthus reaction
[also polyarteritis nodosa and reactive arthritis; most result in nephritis, joint pain, systemic vasculitis, etc.]
55
Immune mechanisms of type IV hypersensitivity
[cell-mediated hypesensitivity]
Activated T cells —> release of cytokines, inflammation, and macrophage activation; T cell mediated cytotoxicity
56
Histopathologic lesions associated with type IV hypersensitivity
Perivascular infiltrates, edema, granuloma formation; cell destruction
57
Prototypical disorders associated with type IV hypersensitivity
Contact dermatitis
Multiple sclerosis
Type I DM
Tuberculosis
[also rheumatoid arthritis, IBD, psoriasis]
58
Immediate vs. late phase reaction with type I hypersensitivity
Immediate reaction: vasodilation, vascular leakage, smooth muscle spasm or glandular secretion — occurs minutes after exposure and subsides w/i a few hours
Late-phase (e.g., allergic rhinitis and bronchial asthma): 2-24 hours after initial exposure and lasts several days. Infiltration with eosinophils, neutrophils, basophils, monocytes, and CD4+
59
Describe activation of mast cells
Activated by cross-linking of high-affinity IgE Fc receptors
IgE coated mast cells are “sensitized” — sensitive to second encounter with specific Ag
[mast cells also triggered by complement components C5a and C3a, chemokines, drugs like codeine and morphine, adenosine, melittin aka bee venom, physical stim like heat/cold/sun]
60
What subset of CD4+ T cells plays an important role in Type I hypersensitivity?
Th2 produces important cytokines
IL-4 stimulates class switching to IgE production + more production of Th2 cells
IL-5 induces development and activation of eosinophils
IL-13 enhances IgE production and acts on epithelial cells to stimulate mucus secretion
Also chemokine production
61
During the late phase rxn of type I hypersensitivity, leukocytes — especially eosinophils — are recruited which amplify and sustain the inflammatory response without Ag present. Eosinophils damage tissue via release of what substances?
Proteolytic enzymes
Major basic protein
Eosinophil cationic protein
62
___ =increased propensity to develop immediate hypersensitivity reactions
Atopy
[have higher serum IgE levels and more IL-4 producing Th2 cells]
63
Non-atopic allergy is responsible for 20-30% of immediate hypersensitivity reactions. What are the triggers for these types of reactions?
Triggered by non-antigenic stimuli like temp extremes and exercise
Does not involve Th2 cells or IgE
Likely d/t mast cells that are abnormally sensitive to activation
64
Examples of Ab-mediated cell destruction and phagocytosis in disease
Transfusion reactions
Hemolytic disease of newborn
Autoimmune hemolytic anemia, agranulocytosis, and thrombocytopenia
Certain drug reactions where drug acts as hapten attaching to PM of RBCs
Myasthenia gravis
Graves disease
65
Mechanism of Ab-mediated cell dysfunction in myasthenia gravis
Abs react with ACh receptors in motor end plates of skeletal muscles and block neuromuscular transmission —> muscle weakness
66
Mechanism of Ab-mediated cell dysfunction in graves disease
Abs against TSH receptors on thyroid epithelial cells stimulate the cells —> hyperthyroidism
67
Decreased serum levels of C3 can be used to detect what type of hypersensitivity?
Type III
68
What 2 subsets of CD4 cells play an important role in type IV hypersensitivities?
Th1 — secrete IFN-y to activate macrophages
Th17 — secrete IL-17, IL-22, chemokines, etc. to recruit neutrophils and monocytes; also produce IL-21 to amplify Th17 response
69
The tuberculin reaction is an example of what type of hypersensitivity response?
Type IV
70
Mechanism of central tolerance in T cells
Negative selection or deletion — via apoptosis
Some may develop into Treg cells
71
Mechanism of central tolerance for B cells
Many will undergo receptor-editing, otherwise undergo apoptosis
72
Mechanisms of peripheral tolerance
Anergy
Suppression by Treg cells
Deletion/apoptosis
73
Immune-privileged sites (no communication with blood and lymph)
Testis
Eye
Brain
74
Diseases associated with DRB1 HLA alleles
Rheumatoid arthritis (anti-CCP Ab positive)
Type I DM
Multiple sclerosis
SLE
75
Disease associated with B*27 HLA allele
Ankylosing spondylitis
76
Disease associated with DQA1 HLA allele
Celiac disease
77
Diseases associated with PTPN22
RA
T1D
IBD
78
Diseases associated with IL23R
IBD
PS
AS
79
Diseases associated with CTLA4
T1D
| RA
80
Diseases associated with IL2RA
MS
| T1D
81
Diseases associated with NOD2 gene
IBD
82
Diseases associated with ATG16 gene
IBD
83
Disease associated with IRF5; IFIH1 genes
SLE
84
Classic example of molecular mimicry
Rheumatic heart disease — Ab against streptococcal proteins cross-react with myocardial proteins and cause myocarditis
85
In what way might infections protect against some autoimmune diseases?
Infections promote low-level IL-2 production, and this is essential for maintaining Treg cell population
86
Disease affecting african american+hispanics more than whites, involves multiple organs like skin, joints, kidney, and serosal membranes, and injury is caused mainly by deposition of immune complexes and binding of Abs to various cells and tissues
SLE
87
Criteria for SLE
```
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
Neurologic disorder
Hematologic disorder
Immunologic disorder
Antinuclear Ab
```
[greater than 4 criteria = SLE]
88
All systemic autoimmune diseases typically have what type of autoantibodies?
Antinuclear antibodies (ANAs)
89
Examples of systemic autoimmune diseases other than SLE
Systemic sclerosis
Sjogren syndrome
Autoimmune myositis
Rheumatoid arthritis
90
Antinuclear Abs are directed against nuclear Ags. What are the 4 categories?
Abs to DNA
Abs to histones
Abs to nonhistone proteins bound to RNA
Abs to nucleolar Ags
91
Antibodies to _______ and ______ are virtually diagnostic of SLE
dsDNA; Smith (Sm) antigen
92
6 patterns of glomerular disease associated with SLE; note which is most common vs. least common
Minimal mesangial lupus nephritis (least common)
Mesangial proliferative lupus nephritis
Focal lupus nephritis
Diffuse lupus nephritis (MOST COMMON/MOST SEVERE)
Membranous lupus nephritis
Advanced sclerosing lupus nephritis
[these are listed in order from class I —> class VI]
93
Rarely, _________ _____ may be the dominant abnormality in glomerular disease associated with SLE
Tubulointerstitial lesions
94
Describe skin changes associated with SLE
Characteristic butterfly rash
Can have similar rash on extremities and trunk; exposure to sunlight incites or accentuates the erythema
Immunoflourescence: deposition of Ig and complement along dermal-epidermal junction — can be present in uninvolved skin (also seen in scleroderma or dermatomyositis)
95
SLE effects on CV system
Any layer of heart can be damaged
Myocarditis can lead to tachycardia and ECG abnormalities
CAD can lead to angina, MI
Valvular abnormalities (mitral and aortic valves) can lead to stenosis and/or regurg
Valvular (aka Libman Sacks) endocarditis — uncommon now d/t steroid tx, aka nonbacterial verrucous endocarditis
96
CNS involvement with SLE
Neuropsychiatric symptoms d/t non-inflammatory occlusion of small vessels; may be d/t endothelial damage by autoantibodies or immune complexes
97
Spleen involvement with SLE
Splenomegaly
Capsular thickening
Follicular hyperplasia
98
Lung involvement with SLE
Pleuritis and pleural effusions
Chronic interstitial fibrosis
Secondary pulmonary HTN
99
SLE effect on blood vessels and joints
Blood vessels — acute necrotizing vasculitis involving capillaries, small arteries, and arterioles
Joints — non-erosive synovitis with little deformity (opposite of RA)
100
Subtype of lupus causing primarily skin manifestations with plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border
Chronic discoid lupus erythematosus
101
Subtype of lupus presenting with predominant skin involvement in which skin rash tends to be widespread, superficial, and non-scarring; most patients have mild systemic symptoms
Subacute cutaneous lupus erythematosus
102
Subset of lupus manifesting as a LE-like syndrome in patients receiving hydralazine, procainamide, isoniazid, D-penicillamine, or anti-TNF therapy — affects multiple organs but renal and CNS involvement is uncommon
Drug-induced lupus erythematosus
103
Chronic disease characterized by keratoconjunctivitis sicca and xerostomia
Sjogren syndrome
104
Biopsy of the lip is required for dx of Sjogrens. What are the intense lymphocytic responses in the tissues involved? (Early vs over time)
Early: mixture of polyclonal T and B cells
Over time: a dominant B-cell clone can emerge —> marginal zone lymphoma
105
Disease characterized by chronic inflammation thought to be result of autoimmunity leading to widespread damage to small blood vessels as well as progressive interstitial and perivascular fibrosis in skin and multiple organs
Systemic sclerosis (scleroderma)
106
Majority of scleroderma pts progress with death from what potential complications?
Renal failure
Cardiac failure
Pulmonary insufficiency
Malabsorption
107
Clinical features of scleroderma
Mostly females 50-60
Skin thickening
Raynaud phenomenon (episodic vasoconstriction of arteries and arterioles of extremities)
Dysphagia from esophageal fibrosis
Respiratory difficulty
Myocardial fibrosis —> arrhythmias or cardiac failure
Renal: mild proteinuria, malignant HTN
108
Some patients with limited scleroderma have what is known as CREST syndrome. What is the combination of symptoms associated with this syndrome?
```
Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
```
109
Disease with clinical features that are a mixture of the features of SLE, systemic sclerosis, and polymyositis
Mixed CT disease (not a distinct entity, can evolve into classic SLE or scleroderma)
110
Serious complications of mixed CT disease
Pulmonary HTN
Interstitial lung disease
Renal disease
111
Relatively new disease most often affecting middle-aged and older men
First characterized in autoimmune pancreatitis and now reported in virtually all organs
Characterized by tissues infiltrated with Ab-producing plasma cells and lymphocytes (mainly T cells), storiform fibrosis and obliterative phlebitis, and usually increased serum Ab levels
IgG4 related disease
112
Recognition of alloantigens in kidney graft via direct vs. indirect path
Direct: donor APC in graft recognized by host T cells; CD4+ secrete IFN-y to activate macrophages, CD8+ cause endothelitis in renal blood vessels and damge renal tubule cells
Indirect: recipients APC recognizes graft cells and presents ingested peptides to CD4+ cells which secrete IFN-y, activating macrophages and damaging renal blood vessels. CD4+ also cause differentiation of B cells into plasma cells which secrete Abs that cause endothelial injury in renal blood vessels
113
Acute vs. chronic T-cell mediated rejection of organs
Acute: within months, associated with clinical and biochemical signs of organ failure, cytokine secretion by CD4s, increased vascular permeability and local accumulation of lymphocytes and macrophages
Chronic: lymphocytes react against alloantigens in vessel wall; secrete cytokines that induce local inflammation
114
Ab-mediated reactions to graft tissue
Hyperacute: occurs when PREFORMED antidonor Abs are present in recipient (d/t previous transplant, prior transfusion, multiparous women)
Acute: antidonor Abs produced after transplant, initial target seems to be graft vasculature
Chronic: insidious development, primarily affects vasculature
115
HLA matching is not typically done in what types of organ transplants?
Liver
Heart
Lungs
116
Types of immunosuppressive therapy
Steroids - reduce inflammation
Mycophenolate mofetil - inhibits lymphocyte prolif
Tacrolimus (FK506) - inhibits T cell function
117
___ virus can reactivate, infect renal tubules and may even cause graft failure; complication of immunosuppression
Polyoma virus
118
Immunosuppression carries risk of re-activation of what latent viruses?
EBV-induced lymphomas
HPV-induced squamous cell carcinomas
Kaposi sarcoma (HHV8)
119
What are hematopoietic stem cell (bone marrow) transplants used for?
Hematologic malignancies
Bone marow failure syndromes like aplastic anemia
Inherited stem cell defects like sickle cell anemia, thalassemia, and immunodeficiency states
120
Disease that occurs when immunologically competent cells or their precursors are transplanted into immunologically crippled recipients
Graft-vs-Host disease (GVHD)
The transferred cells recognize alloantigens in host and attack host tissues
Seen MOST COMMONLY in setting of HSC transplantation; rarely occurs in transplant of solid organs or transfusions of un-irradiated blood
121
GVHD is mediated by T cells contained in transplanted donor cells, so the disease can be eliminated by depleting donor T cells prior to transfusion. This can have what complications?
Recurrence of tumor in leukemic patients
Increased incidence of graft failures
Increased rates of EBV-related B cell lymphoma
122
Inherited defects in innate immunity
LAD 1 (mutations in beta chain of integrins)
LAD2 (mutations in selectin receptor)
Chediak-Higashi (mutations affecting lysosome membrane traffic)
CGD (decreased oxidative burst)
MPO deficiency (decreased microbial killing)
```
C2,C4 def (defective classic path)
C3 def (all complement functions defective)
Complement regulatory protein def (excess activation, angioedema, paroxysmal hemoglobinuria)
```
123
Defects in both humoral and cell mediated responses in which infants present with thrush, diaper rash, FTT, GVHD rash, and recurrent infections
SCID (usually x linked, also can be AR)
124
Failure of B cell precursors to develop into mature B cells, serum levels of all classes of Ig are depressed and plasma cells are absent throughout the body
X-linked agammaglobulinemia (bruton)
125
X-linked agammaglobulinemia puts patients at risk for infections that rely on Abs to clear them — what are some examples?
Recurrent bacterial infections of respiratory tract — H.influenzae, Strep pneumoniae, Staph aureus
Viruses in bloodstream or mucosal secretions — enteroviruses like echovirus, poliovirus, and coxsackivirus
Giardia lamblia (intestinal protozoan)
126
Etiology of DiGeorge syndrome and the consequences
Failure of development of 3rd and 4th pharyngeal pouches which usually give rise to thymus, parathyroids, C cells of thyroid, ultimobranchial body
Leads to loss of T cell mediated immunity (poor defense against fungal and viral infections), hypocalcemia induced tetany, and congenital defects of heart and great vessels, abnormal appearance of mouth, ears, facies
Component of 22q11 deletion syndrome
127
Disorder caused by defect in ability of helper T cells to deliver activating signals to B cells and macrophages, typically X-linked, and presents with recurrent pyogenic infections and/or pneumocystis jiroveci pneumonia
Hyper-IgM syndrome
128
Group of disorders with hypogammaglobulinemia that can be sporadic or inherited form. Patients have normal/near-normal level of B cells but they aren’t ablel to differentiate into plasma cells. Clinically resembles X-linked agammaglobulinemia but M=F
Common variable immunodeficiency (CVID)
129
Disease that can be familial or acquired in association with toxoplasmosis, measles, or other viral infection. Most patients are asymptomatic but those who have symptoms tend to have recurrent sinopulmonary infections and diarrhea as well as high frequency of respiratory tract allergy and autoimmune diseases like SLE, RA, and celiac
Isolated IgA deficiency — extremely low levels of both serum and secretory IgA
130
X-linked immunodeficiency characterized by thrombocytopenia, eczema, and recurrent infections leading to early death if not treated with HSC transplant
Wiskott aldrich syndrome
131
Autosomal recessive immunodeficiency characterized by abnormal gait, vascular malformations, neurologic deficit, increased incidence of tumors, and immunodeficiency
Ataxia telangiectasia
132
Modes of HIV transmission
Sexual transmission
Parenteral transmission
Mother-to-infant
133
Mechanisms of parenteral transmission of HIV
IV drug abusers (needle sharing)
Hemophiliacs who received factor VIII and IX concentrates
Recipients of blood transfusions
134
Mechanisms of mother-to-infant transmission of HIV
In utero by transplacental spread
During delivery through infected birth canal
After birth by ingestion of breast milk
135
HIV first infects which cells? What do these cells have in common?
T cells
DCs
Macrophages
[all have CD4]
136
Major abnormalities in immune function in AIDS
Lymphopenia
Decreased T cell function in vitro and in vivo
Polyclonal B cell activation
Altered monocyte/macrophage functions
137
HIV 1 can infect and multiply in terminally non-dividing macrophages, dependent on ____ gene
Vpr
138
DCs role in HIV
Mucosal DCs — infected and transport to regional LNs then transmit to CD4 T cells. Lectin like receptor specifically binds HIV and displays it in intact infectious form to T cells
Follicular DCs in LNs — potential reservoirs, most virus particles found on their dendritic processes, trap virions coated with anti-HIV Abs thus retaining ability to infect CD4+ cells
139
B cells and HIV
Polyclonal activation of B cells —> GC hyperplasia, bone marrow plasmacytosis, hypergammaglobulinemia, formation of circulating immune complexes
Can’t mount Ab responses to newly encountered Ag
140
HIV and the brain
Nervous system is major target; HIV infects macrophages and microglial cells
141
HIV shows few or no clinical manifestations during clinical latency period. What are some examples?
Thrush, vaginal candidiasis, herpes zoster, mycobacterial Tb, autoimmune thrombocytopenia
142
How does HIV evade immune detection
Destroys CD4 cells critical for effective immunity
Antigenic variation
Down-modulation of Class I MHCs on infected cells so viral Ags aren’t recognized by CD8
May also evolve and switch from relying solely on CCR5 to enter target cell to relying on either CXCR4 or both
143
Clinical features of AIDS
```
Fever and weight loss
Diarrhea
Generalized lymphadenopathy
Neurologic disease
Multiple opportunistic infections
Secondary neoplasms
```
144
Tx for HIV and potential downsides
HAART — highly active antiretroviral therapy
Downsides = immune reconstitution inflammatory syndrome, adverse side effects like lipoatrophy, lipoaccumulation, elevated lipids, insulin resistance, peripheral neuropathy, permature CV, kidney, and liver disease
145
Extracellular deposits of fibrillar proteins leading to tissue damage and functional compromise
Amyloidosis
146
AIDS-defining protozoal and helminthic infections
Cryptosporidiosis or isosporidiosis (enteritis)
Pneumocystosis (pneumonia or disseminated infection)
Toxoplasmosis (pneumonia or CNS infection)
147
AIDS-defining fungal infections
Candidiases (esophageal, tracheal, pulmonary)
Cryptococcosis (CNS infection)
Coccidioidomycosis (disseminated)
Histoplasmosis (disseminated)
Pneumocystis jiroveci
148
AIDS-defining bacterial infections
Mycobacteriosis (atypical, e.g., mycobacterium avium-intracellulare, disseminated or extrapulmonary; mycobacterium tuberculosis)
Nocardiosis (pneumonia, meningitis, disseminated)
Salmonella infections, disseminated
149
AIDS-defining viral infections
CMV (pulmonary, intestinal, retinitis, or CNS)
HSV (localized or disseminated)
Varicella-zoster virus (localized or disseminated)
JC virus — progressive multifocla leukoencephalopathy
150
AIDS-defining neoplasms
Kaposi sarcoma (HHV8)
Primary lymphoma of brain (HBV)
Invasive cancer of uterine cervix or anus (HPV)
151
Ig light chains are known as ________ proteins when found in the urine
“Bence Jones”
152
Amyloidosis may occur due to production of abnormal amounts of protein d/t:
—Acquired mutations in Ig light chains which undergo limited proteolysis to form ____ proteins which deposit in tissues
—Chronic inflammation, macrophage activation, IL-1 and IL-6 release causing release of SAA protein from the liver, which undergoes limited proteolysis to form ____ proteins which deposit in tissues
AL
AA
153
Amyloidosis may also occur d/t production of normal amounts of mutant protein such as mutant transthyretin, which aggregates to form deposits of ____ protein
What diseases would this be associated with?
ATTR
Familial amyloidotic neuropathies (several types)
Systemic senile amyloidosis
154
Associated diseases, major fibril protein, and chemically related precursor protein in immunocyte dyscrasias with amyloidosis (primary amyloidosis)
Multiple myeloma and other monoclonal plasma cell proliferations
Major protein = AL
Precursor = Ig light chains, chiefly gamma type
155
Associated diseases, major fibril protein, and chemically related precursor protein in reactive systemic amyloidosis (secondary amyloidosis)
Chronic inflammatory conditions
Major protein = AA
Precursor = SAA
156
Associated diseases, major fibril protein, and chemically related precursor protein in hemodialysis-associated amyloidosis
Chronic renal failure
Major protein = AB2m
Precursor = B2-microglobulin (component of MHC molecules)
157
Associated diseases, major fibril protein, and chemically related precursor protein in senile cerebral amyloidosis
Alzheimer disease
Major protein = AB
Precursor = APP
158
Major fibril protein and chemically related precursor protein involved in familial mediterranean fever
AA
Precursor = SAA
159
General structural effect amyloid has on organs
Progressive accumulation —> encroachment and pressure atrophy of adjacent cells
160
Organ involvement in amyloidosis
Secondary to chronic inflamm: kidneys, liver, spleen, LNs, adrenals, thyroid
Amyloidosis associated with plasma cell proliferations: heart, GI tract, respiratory tract, peripheral nerves, skin, and tongue (but not specific)
161
Clinical features of amyloidosis
Incidental finding with no clinical manifestations
Cause serious clinical problems and even death
Symptoms depend on magnitude of deposits and sites or organs affected
Initial clinical manifestations are nonspecific — weakness, weight loss, light-headedness, or syncope
Prognosis for generalized amyloidosis is poor
