Disorders of the Immune System (P) Flashcards
What are the 3 broad categories of the disorders of IS?
1) Hypersensitivity rxns
2) Autoimmune diseases
3) Immunologic deficiency syndromes
*Amyloidosis
What are the types of hypersensitivity rxns?
1) Immediate hypersensitivity
2) Cytotoxic (Ab-mediated) hypersensitivity
A. Opsonization and complement and Fc receptor-mediated phagocytosis
B. Complement and Fc receptor mediated inflammation
C. Antibody mediated cell dysfunction
3) Immune complex mediated hypersensitivity
4) Cell mediated hypersensitivity
A. Delayed type hypersensitivity
B. T-cell mediated hypersensitivity
What is the other term for immediate hypersensitivity?
Type I hypersensitivity
What is the principle of immediate (type I) hypersensitivity?
Rapidly developing immunologic rxn occurring within mins after the combination of an Ag w/ Ab bound to mast cells in individuals previously sensitized to the Ag
What is the role of IgE Abs to type I hypersensitivity?
It is mediated by IgE Abs directed against sp Ags (allergens)
What is the mechanism of type I hypersensitivity?
Ag + Ab (IgE) bound to mast cells / basophils immediate release of vasoactive amines and other mediators from mast cells; recruitment of inflammatory cells
What is the other term for antibody-mediated hypersensitivity?
Type II hypersensitivity
What is antibody-mediated (type II) hypersensitivity?
It is mediated by Abs against intrinsic Ags or extrinsic Ags adsorbed on cell surfaces or ECM
What is the mechanism of type II hypersensitivity?
Ab (IgG or IgM) + Ag (bound to cell surface or ECM)
*What is the process (or steps) of type II hypersensitivity?
1) Opsonization and phagocytosis
2) Complement and Fc receptor-mediated inflammation
3) Antibody-mediated cellular dysfunction
*What are the diseases / disorders that causes type II hypersensitivity?
1) Autoimmune hemolytic anemia
2) Autoimmune thrombocytopenic purpura
3) Goodpasture syndrome
4) Myasthenia gravis
5) Graves disease (hyperthyroidism)
6) Insulin-resistance DM
What are the ff w/ regards to the given disorder:
1) What is/are the target Ags of the given disorder?
2) What is the mechanism of the given disorder?
Given disorder: Autoimmune hemolytic anemia
1) RBC membrane proteins
2) IIa opsonization and phagocytosis of erythrocytes
What are the ff w/ regards to the given disorder:
1) What is/are the target Ags of the given disorder?
2) What is the mechanism of the given disorder?
Given disorder: Autoimmune thrombocytopenic purpura
1) PLT membrane proteins (GpIIb:IIIa *opr GpIb/IX)
2) IIa opsonization and phagocytosis of PLTs
What are the ff w/ regards to the given disorder:
1) What is/are the target Ags of the given disorder?
2) What is the mechanism of the given disorder?
Given disorder: Goodpasture syndrome
1) Noncollagenous protein in BM of alveoli and glomeruli
2) IIb complement and Fc receptor mediated inflammation
What are the ff w/ regards to the given disorder:
1) What is/are the target Ags of the given disorder?
2) What is the mechanism of the given disorder?
Given disorder: Myasthenia gravis
1) Acetylcholine receptor
2) IIc Ab inhibits Ach binding; down regulates receptors
What are the ff w/ regards to the given disorder:
1) What is/are the target Ags of the given disorder?
2) What is the mechanism of the given disorder?
Given disorder: Graves disease
1) TSH receptor
2) IIc Ab-mediated stimulation of TSH receptors
What are the ff w/ regards to the given disorder:
1) What is/are the target Ags of the given disorder?
2) What is the mechanism of the given disorder?
Given disorder: Insulin-resistance DM
1) Insulin receptor
2) IIc Ab inhibits binding of insulin
What is the other term of immune-complex mediated hypersensitivity?
Type III hypersensitivity
What is the mechanism of immune-complex mediated (type III) hypersensitivity?
(all *)
Ag + Ab AgAb complex
(in circulation or in situ)
Activate complement
Attract neutrophils
Release lysosomal enzymes
*What are the types of type III hypersensitivity?
1) Systemic or
2) Local
*What are the diff phases of type III hypersensitivity?
1) Phase I
2) Phase II
3) Phase III
What is the action that happen in phase I?
Formation of Ag-Ab complexes in the circulation
What is the action that happen in phase II?
Deposition of the immune complexes in various tissues
What is the action that happen in phase III?
1) Inflammatory rxn at the sites of immune complex deposition
2) Clinical features appear
*What are the characteristics of type III hypersensitivity?
1) Presence of acute necrotizing vasculitis
2) Fibrinoid necrosis
*What are the diff diseases that causes type III hypersensitivity?
1) SLE
2) Polyarteritis nodosa
3) Post streptococcal glomerulonephritis
4) Acute glomerulonephritis
5) Arthus reaction
6) Serum sickness
Answer the ff questions w/ regards to the given disease:
1) What is/are the Ags involved?
2) What is/are the clinical manifestations of the given disease?
Given disease: SLE
1) DNA, nucleoproteins, others
2) Nephritis, arthritis, and vasculitis
Answer the ff questions w/ regards to the given disease:
1) What is/are the Ags involved?
2) What is/are the clinical manifestations of the given disease?
Given disease: Polyarteritis nodosa
1) Hep B surface Ags
2) Vasculitis
Answer the ff questions w/ regards to the given disease:
1) What is/are the Ags involved?
2) What is/are the clinical manifestations of the given disease?
Given disease: Post streptococcal glomerulonephritis
1) Streptococcal cell wall Ag(s) may be planted in GBM
2) Nephritis
Answer the ff questions w/ regards to the given disease:
1) What is/are the Ags involved?
2) What is/are the clinical manifestations of the given disease?
Given disease: Acute glomerulonephritis
1) Bacterial, parasite, and tumor Ags
2) Nephritis
Answer the ff questions w/ regards to the given disease:
1) What is/are the Ags involved?
2) What is/are the clinical manifestations of the given disease?
Given disease: Arthus reaction
1) Various foreign proteins
2) Cutaneous vasculitis
Answer the ff questions w/ regards to the given disease:
1) What is/are the Ags involved?
2) What is/are the clinical manifestations of the given disease?
Given disease: Serum sickness
1) Various proteins (e.g. *forein serum)
2) Arthritis, vasculitis, and nephritis
What is the other term for T-cell mediated hypersensitivity?
Type IV hypersensitivity
T-cell mediated (type IV) hypersensitivity is initiated by what?
By Ag-activated (sensitized) lymphocytes
*What are the 2 types of type IV hypersensitivity?
1) Delayed type hypersensitivity
2) T-cell mediated cytotoxicity
*What cells are involved in delayed type hypersensitivity?
CD4+ T cells
*Principal pattern?
What are the cytokines released if delayed type hypersensitivity is present?
1) IFN gamma(sign)
2) IL-2
3) TNF and lymphotoxin
What is the function of IFN gamma(sign)?
For the activation of macrophages
What is the function of IL-2?
For the proliferation of T cells
What are the functions of TNF and lymphotoxin?
1) For the extravasation of lymphocytes and monocytes
2) For granuloma formation
*What cells are present if T-cell mediated cytotoxicity is present?
CD8+ T cells
What may contribute to graft rejection?
Response to:
1) Viral infections
2) Tumor cells
What are the 2 pathways that mediates T-cell mediated cytotoxicity?
1) Perforin-granzyme-dependent killing
2) Fas-fas ligand- dependent killing
- Answer the ff questions w/ regards to the given type of hypersensitivity:
1) What are the prototype disorders present?
2) What is/are the immune mechanism/s by the given hypersensitivity?
Given hypersensitivity: Immediate hypersensitivity
1) Anaphylaxis; allergies and bronchial asthma (atopic forms)
2) Production of IgE Abs; immediate release of vasoactive amines and other mediators from mast cells
- Answer the ff questions w/ regards to the given type of hypersensitivity:
1) What are the prototype disorders present?
2) What is/are the immune mechanism/s by the given hypersensitivity?
Given hypersensitivity: Ab-mediated hypersensitivity
1) AIHA (IIa), Goodpasture syndrome (IIb), graves, and myasthenia gravis (IIc)
2) Production of IgG, IgM; binds to Ag on target cells or tissue; phagocytosis or lysis of target cell by C8, C9 (IIa), or inflammation (IIb) or cellular dysfunction (IIc)
- Answer the ff questions w/ regards to the given type of hypersensitivity:
1) What are the prototype disorders present?
2) What is/are the immune mechanism/s by the given hypersensitivity?
Given hypersensitivity: Immune complex-mediated hypersensitivity
1) SLE, some forms of GN, serum sickness, and Arthus rxn
2) Deposition of Ag-Ab complexes; complement activation; recruitment of leukocytes; release of lysosomal enzymes and toxic moieties
- Answer the ff questions w/ regards to the given type of hypersensitivity:
1) What are the prototype disorders present?
2) What is/are the immune mechanism/s by the given hypersensitivity?
Given hypersensitivity: Cell-mediated hypersensitivity
1) TB (IVa), response to viral infections (IVb), and transplant rejection
2) Activated T lymphocytes; i) release of cytokines and macrophage activation; ii) T cell-mediated cytotoxicity
Autoimmune diseases result from what?
These results from tissue injury caused by T cells or Abs that react against self-Ags
What are the general features of autoimmune diseases?
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) Pts often have increased Ig in the serum
*Spectrum of autoimmune diseases
What are the clinical features of SLE?
1) Female > male (10:1 - 20:1)
2) 2nd - 3rd decade: acute
-> older pts: less acute and better prognosis
3) Most common signs and symptoms:
A. Hematologic: 100%
B. Musculo-skeletal (arthritis): 90%
C. Skin (butterfly rash): 85%
D. Fever: 83%
E. Renal, pulmonary, cardiac: 30 - 50%
4) Course:
A. Acute: death within wks - mos
B. Chronic: w/ treatment; 10 - 20 yrs
-> most common cause of death: renal failure, then next is infection
5) Some factors related to pathogenesis:
A. Genetic: associated w/ IgA, C2 deficiency; greater chance in family grps associated w/ certain haplotypes
B. Environmental: drugs, U.V. light, and hormones
C. Immunologic
What are the 2 mechanisms of tissue damage?
1) Immune complex disease (type III)
2) Abs directed against cell types (type II)
*What are the mechanisms present to immune complex disease (type III)?
1) Abs against DNA
2) Abs to histones
3) Abs to nonhistone proteins bound to RNA
4) Abs to nucleolar Ags
*The mechanisms present in immune complex disease (type III) causes what?
1) Vasculitis in small arteries and arterioles
- > in spleen, characteristic “onion-skin” lesions
2) Glomerulonephritis: type of w/c depends on size and dose
- > 5 patterns:
1) minimal or no detectable abnormality (class I)
2) mesangial (class II)
3) focal proliferative (class III)
4) diffuse proliferative (class IV): most common; most serious
5) membranous GN class (class V)
3) Arthritis
4) Heart: pericarditis
- > Libmann-Sacks endocarditis
5) Skin
*What are the other mechanisms of tissue damage?
1) Interstitial pneumonitis
2) Cerebral infarcts and hemorrhages
3) Pericarditis
*Abs directed against cell types (type II) has mechanisms whereas Abs are against what?
1) RBC: anemia
2) WBC: leukopenia
3) PLTs: thrombocytopenia
*What are the typical features of SLE?
1) History and PE: young female w/ malar rash, fever, joint pains, and hematologic problem
2) (+) ANA (peripheral pattern)
3) Ab to dsDNA and Smith (Sm) Ag
4) (+) lupus band test on skin biopsy
5) Decreased complement lvl (part C3)
6) Renal biopsy shows glomerulonephritis and immune complex deposits by immunofluorescence
What are the 1997 revised criteria for classification of SLE?
1) Malar rash
2) Discoid rash
3) Photosensitivity
4) Oral ulcers
5) Arthritis
6) Serositis
7) Renal disorder
8) Neurologic disorder
9) Hematologic disorder
10) Immunologic disorder
11) Antinuclear Ab
What are the characteristics of malar rash?
1) Fixed erythema
2) Flat or raised
3) Over the malar eminences
What are the characteristics of discoid rash?
1) Erythematosus raised patches
2) W/ adherent keratotic scaling
3) W/ follicular plugging
4) Atrophic scarring may occur
What is the characteristic of photosensitivity?
It is a skin rash as a result of exposure to UV light
What are the characteristics of oral ulcers?
1) Oral or nasopharyngeal ulceration
2) It is usually painless
3) These are observed by a physician
What are the characteristics of arthritis?
1) Nonerosive arthritis involving 2 or more peripheral joints
2) It is characterized by tenderness
3) It is characterized by swelling
4) It is characterized by effusion
*What are the characteristics of serositis?
1) Pleuritis: convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion; or
2) Pericarditis: documented by electrocardiogram or rub or evidence of pericardial effusion
*What are the characteristics of renal disorder?
1) Persistent proteinuria 0.5 g/dL > or 3+ > if quantitation not performed; or
2) Cellular casts: may be RBC, hgb, granular, tubular, or mixed
*What are the characteristics of neurologic disorder?
1) Seizures: in the absence of offending drugs or known metabolic derangements (e.g. uremia, ketoacidosis, or electrolyte imbalance); or
2) Psychosis: in the absence of offending drugs or known metabolic derangements (e.g. uremia, ketoacidosis, or electrolyte imbalance)
*What are the characteristics of hematologic disorder?
1) Hemolytic anemia: w/ reticulocytosis, or
2) Leukopenia: < 4.0 x 10^9/L (4,000/uL) total on 2 or more occasions; or
3) Lymphopenia: < 1.5 x 10^9/L (1,500/uL) on 2 or more occasions; or
4) Thrombocytopenia: < 100 x 10^9/L (100 x 10^3/uL) in the absence of offending drugs
*What are the characteristics of immunologic disorder?
1) It has anti-ds DNA
2) It has anti-Sm
3) It has antiphospholipid
What is the characteristic of antinuclear antibody?
It is an abnormal titer of antinuclear Ab by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated w/ drug-induced lupus syndrome
*What are the types of immunodeficiency diseases?
1) Primary
2) Secondary
*What are the characteristics of primary type of immunodeficiency diseases?
1) It is almost genetically determined
2) It is usually X-linked
3) It is seen during infancy (6 mos - 2 yrs)
4) It is associated w/ recurrent infections
*The secondary type of immunodeficiency diseases result from what?
From altered immune function such as malnutrition, viral infection / irradiation, use of immunosuppressive drugs, and lymphoproliferative diseases
*Based on primary components, what are the diff deficiencies present?
1) Stem cell deficiency
2) B-cell deficiency
3) T-cell deficiency
4) Deficiency of myeloid elements
5) Complement deficiency
What are the characteristics of Bruton’s X-linked agammaglobulinemia?
1) It is an ex of B-cell deficiency
2) Lack of mature B cells in the circulation
3) Serum of all Igs are depressed
4) T cell #s are normal
5) T cell function are normal
Provide a classic ex of B-cell deficiency
Bruton’s X-linked agammaglobulinemia
What is the characteristic of the ff w/ regards to B-cell deficiency:
1) Humoral response
2) Cell mediated response
1) Double decrease
2) Normal
*If a pt has B-cell deficiency, the pt are susceptible to what types of infections?
The pt is susceptible to infections caused by pyogenic bacteria (such as staphylococcus, pneumococcus, etc)
What is the treatment for B-cell deficiency?
Gamma(sign) globulin
What are the pathologic findings if a pt has B-cell deficiency?
B cells almost absent in:
1) Lymph nodes
2) Spleen
3) Bone marrow
4) Connective tissue
What is the cause of T cell deficiency?
Failure of the development of the 3rd and 4th pharyngeal pouches
*What are the effects of T cell deficiency?
1) Occurrence of thymic hypoplasia or aplasia
2) Occurrence of parathyroid hypoplasia
3) Congenital defects of the heart and great vessels
4) Presence of dysmorphic facies
What is the cause of thymic hypoplasia or aplasia?
T-cell deficiency
What is the cause of parathyroid hypoplasia?
Tetany
What is the classic ex of T-cell deficiency?
Di George’s syndrome
- What is the characteristic of T-cell deficiency to the ff:
1) Humoral response
2) Cell mediated response
1) Decrease
2) Double decrease
A pt w/ T-cell deficiency is susceptible to what types of infections?
Susceptible to infections caused by intracellular microbes (virus, fungi, and T.B.)
What is the treatment for T-cell deficiency?
Thymus graft
What are the pathologic findings for a pt having T-cell deficiency?
1) Low circulating T-lymphocytes
2) Depleted T-dependent paracortical areas of lymph node and T-dependent areas of spleen
3) Plasma cells normal in # in lymphoid tissues
What is the meaning of SCID?
Severe Combined Immunodeficiency Diseases
What is the classic ex of stem cell defect?
SCID
- What is the characteristic of SCID to the ff:
1) Humoral response
2) Cell mediated response
1) Double decrease
2) Double decrease
A pt having stem cell defect is susceptible to what type/s of infection/s?
Susceptible to all types
What is the treatment for stem cell defect?
Bone marrow graft
What are the pathologic findings for a pt w/ stem cell defect?
1) Absence of T cells and B cells in blood
2) Absence of T cells and B cells in lymph nodes
3) Absence of T cells and B cells in spleen
4) Thymus devoid of lymphoid cells or Hassal’s corpuscles
*What are the characteristics of complement deficiency?
1) It is associated w/ increased susceptibility to bacterial infections (particularly C3)
2) It is associated w/ high incidence of connective tissue diseases (C2 and C4 deficiency w/ SLE)
*What are the complement proteins that are common complement deficiencies?
1) C1 inhibitor
2) C2
3) C3
4) C5 - C9
*What are the characteristics of C1 inhibitor?
1) Presence of angioneurotic edema
2) Presence of edema affecting the skin and mucosal surfaces (e.g. larynx and GIT)
3) Presence of asphyxia
4) Presence of nausea
5) Presence of vomiting
6) Presence of diarrhea after emotional stress
C2 complement deficiency is associated w/ what?
W/ connective tissue diseases (SLE)
C3 complement deficiency is associated w/ what?
W/ frequent bacterial infection
C5 - C9 complement deficiencies are associated w/ what?
W/ repeated Neisseria infections
*What are the diff types of HIV?
1) HIV1
2) HIV2
3) HIV subtype AE
What is the etiology of AIDS?
1) HIV1: in U.S., Central Africa, Europe, and Asia
2) HIV2: in West Africa
3) HIV subtype AE: in the Philippines
In terms of epidemiology, what are the groups that are at risk for acquiring AIDS?
1) Homosexuals or bisexual males
2) IV users
3) Hemophiliacs
4) Blood transfusion recipients
5) Heterosexual contacts
In terms of epidemiology, what are the ways on transmitting AIDS?
1) Via sexual contact
2) Parenteral
3) From infected mother to newborn
In terms of pathogenesis, what are the 2 major targets of HIV?
1) IS
2) CNS
In terms of pathogenesis, what are the immunologic alterations present if a pt has AIDS?
1) Loss of CD4^+ T cells (helper cells)
2) Macrophages are infected
3) Presence of abnormalities of B cell function
4) Due to these immunologic alterations, there is a loss of cell mediated and humoral responses
*In terms of pathogenesis, what are the diff natural histories of AIDS?
1) Acute retroviral syndrome
2) Middle chronic phase
3) Final or crisis phase (full blown AIDS)
What are the characteristics of acute retroviral syndrome (in terms of pathogenesis of AIDS)?
1) It is self-limited
2) It is an acute flu-like illness
What are the characteristics of middle chronic phase (in terms of pathogenesis of AIDS)?
1) The pt is asymptomatic or
2) The pt has generalized lymphadenopathy
*If young homosexual or IV drug users has HIV, what is the clinical feature present (in relation to test done)?
(+) HIV Ab test
What are the characteristics of AIDS in its early and middle phase?
1) Presence of acute symptoms
2) Presence of generalized-lymphadenopathy
*What is the characteristic of AIDS if it is in its late stage?
AIDS indicator diseases
If the AIDS of the pt is already in its late stage, what are the conditions or disorders that the pt will experience?
1) Infections
2) Neoplasms
3) Neurologic effects
The infections present if the pt already has AIDS in its late stage are characterized as being what?
Opportunistic
What are the infections that are present if the pt already has AIDS in its late stage?
1) Pneumocystis carinii pneumonia
2) Fungal infections
What are the neoplasms present if the pt already has late stage of AIDS?
1) Kaposi sarcoma
2) B-cell Non Hodgkin lymphoma
3) Primary lymphoma of the brain
4) Invasive cancer of the uterine cervix
What are the neurologic effects present if the pt has already late stage of AIDS?
1) Aseptic meningitis
2) Peripheral neuropathy
3) Progressive encephalopathy (AIDS-dementia complex)
In terms of morphology, what are the characteristics of AIDS?
1) It is non-specific
2) It is a widespread opportunistic infection
*What are the malignant neoplasms present for pt w/ AIDS?
1) Kaposi’s sarcoma
2) Lymphoma B-cell NHL
*What is the condition present in the lymph nodes of a pt having early stage of AIDS?
Follicular hyperplasia
*Follicular hyperplasia is present in the lymph nodes of a pt w/ early stage of AIDS due to what?
B-cell activation
*What conditions are present in the lymph nodes of a pt w/ late stage of AIDS?
1) Follicular involution
2) Generalized lymphocytic depletion
*In terms of morphology, what are the neurologic effects of AIDS to a pt?
1) Aseptic meningitis
2) Peripheral neuropathy
3) Progressive encephalopathy (AIDS-dementia complex)
*What is the prognosis for a pt w/ AIDS?
Dismal
