Immunology Flashcards
Immunoglobulin heavy chains: Domains.
One variable domain and 3-4 constant domains.
Paratope: Definition.
The part of the immunoglobulin molecular that binds the antigen.
Location of genes for immunoglobulin light chains and heavy chains.
Light chains: Chromosomes 2 (κ) and 22 (λ).
Heavy chains: Chromosome 14.
First step in rearrangement of immunoglobulin genes in B cells.
Rearrangement of genes for variable regions: V and J regions of light chains and V, D, and J regions of heavy chains.
Second step in rearrangement of immunoglobulin genes in B cells.
The rearranged sequences of the variable regions are joined to a gene sequence of a constant region of a light chain or heavy chain. The initial heavy-chain constant region is always μ.
Immunoglobulins on mature B cells.
IgM and IgD.
What happens when a helper T cell stimulates a mature B cell?
The B cell proliferates, and each progeny joins its prefabricated variable-gene sequences to a gene for a different heavy chain. This is isotope switching.
Idiotope: Definition.
The part of the (variable region of the) immunoglobulin molecule that can function as an epitope.
Which classes of immunoglobulin have subclasses?
IgG: 4 subclasses.
IgA: 2 subclasses.
Which classes of immunoglobulin can activate complement?
IgG1, IgG3, IgM: Classic pathway.
IgA: Alternate pathway.
Which class of immunoglobulin is the least abundant?
IgE.
Genes for the T-cell receptor:
A. Number.
B. Location.
A. Four genes: α, β, γ, δ.
B. Chromosome 7.
Types of T-cell receptors.
αβ: 95% of T lymphocytes.
γδ: Mostly in mucous membranes and skin.
NK cells:
A. Percentage of circulating lymphocytes.
B. TCR and immunoglobulin.
A. About 10%.
B. Not expressed; genes remain in germline state.
NK cells: Surface markers.
Positive: CD16, CD56, CD57.
Negative: CD3.
NK cells: Purpose of CD16.
As the FcγR, it binds opsonized cells, mediating antigen-dependent cytotoxicity.
NK cells: Functions.
Combating virus-infected cells and tumor cells.
Secreting IFNγ.
Antigen-presenting cells: Immunity-mediating antigens expressed on their surfaces.
All: MHC class II, CD68, lysozyme.
All but monocytes and macrophages: S100, CD1a.
Antigen-presenting cells: Secretion.
Interleukin 1.
Chemokine that attracts neutrophils.
Interleukin 8 (among others).
How basophils and mast cells come to release the contents of their granules.
They use their Fcε to bind IgE, the cross-linking of which promotes degranulation.
Cytokines that stimulate eosinophils.
IL-4 stimulates production of IgE.
IL-5 attracts eosinophils.
Both interleukins are secreted by Th2 cells.
Charcot-Leyden crystals:
A. Origin.
B. Function.
A. Degranulation of eosinophils.
B. They have lysophospholipase activity.
Complement: Final common pathway.
Formation of C5b6789, the membrane-attack complex.
Complement: Activators of the classic pathway.
Antigen-antibody complexes of IgG or IgM.
Complement: Classic pathway to the formation of the C3 convertase.
The Fc portion of the immunoglobulin molecule binds to C1q. Activated C1 catalyzes the formation of C4b2a.
Complement: Classic pathway from the formation of the C3 convertase.
C4b2a converts C3 to C3a and C3b. The latter joins the complex to make C4b2a3b, the C5 convertase, which yields C5b.
Complement: Alternative pathway to the formation of the C3 convertase.
Constitutively produced C3b binds to Bb (produced by the action of factor D on factor B). This C3bBb is the C5 convertase.
Complement: Alternative pathway from the formation of the C3 convertase.
C3Bb acts on C3 to make more C3b. The resulting C3Bb3b is the C5 convertase.
Complement: Regulators of the alternative pathway.
Factor I inactivates C3 unless the latter is bound, for example, to a bacterial cell wall.
Properdin stabilizes the C3 and C5 complexes.
Complement: Activators of the mannan-binding-lectin pathway.
Carbohydrates of non-mammalian cells, specifically those of Salmonella, Listeria, Neisseria, Candida, Cryptococcus.
Complement: Mannan-binding-lectin (MBL) pathway to the association with MASPs.
Binding of mannose-binding lectin binds to the microbial surface allows MBL to associate with MASPs (MBL-associated serine proteases).
Complement: Mannose-binding-lectin pathway from the association with MASPs.
MASP-2 cleaves C4 and C2, thus bypassing C1 and obviating the need for antigen-antibody complexes. C4b2a is the C3 convertase.
Complement: The anaphylotoxins.
C3a and C5a, which promote the release of histamine from basophils.
Complement: Rôle of decay-accelerating factor.
Accelerates the decay of the C3 and C5 convertases.
Complement: Activators of the alternative pathway.
Bacterial cell walls, venoms, endotoxins, complexed IgA.
HLA class I molecules: Components.
Heavy chain: Three α domains.
Light chain: β₂-microglobulin.
HLA class I molecules: Distribution on body cells.
Found on most nucleated cells.
HLA class I molecules: Function.
Mediation of the function of CD8-positive T cells, which kill cells that express foreign antigen in conjunction with their class I molecules.
HLA class II molecules: Components.
An α chain and a β chain, each of which has
Two domains similar to the immunoglobulin light chains.
A transmembrane domain.
HLA class II molecules: Distribution on body cells.
Found on B cells, antigen-presenting cells, and activated T cells.
Primary immunodeficiencies: Who is mainly affected?
Males.
Defects of immunoglobulins or of B cells: Clinical manifestations.
Recurrent bacterial infections of the respiratory tract, ultimately leading to bronchiectasis.
Recalcitrant intestinal infections such as with Giardia intestinalis.
Defects in T cells: Clinical manifestations.
Viral and fungal infections, e.g. mucocutaneous candidiasis.
Defects of phagocyte: Clinical manifestations.
Infections by staphylococci and other catalase-positive organisms.
Defects in terminal components of complement: Clinical manifestations.
Severe infections by encapsulated organisms such as N. meningitidis and S. pneumoniae.
Primary immunodeficiencies: Possible findings on physical examination.
Large lymph nodes: Common-variable immunodeficiency, chronic granulomatous disease.
Small lymph nodes: Other B-cell deficiencies.
Petechiae, easy bruising: Wiskott-Aldrich syndrome.
How injection of antigens can be used to determine the type of immunological defect.
Impaired response to protein antigens (tetanus toxoid, diphtheria toxoid): Defect in T cells, B cells, or both.
Impaired response to carbohydrate antigens (pneumococcal or meningococcal vaccine): Defect in B cells.
RAST:
A. Meaning.
B. Principle.
A. Radioallergosorbent test.
B. The amount of IgE production elicited by an antigen is measured.
Specific tests of T-cell function.
Flow cytometry.
Tests of delayed-type hypersensitivity.
Proliferation assays.
Proliferation assays for T cells:
A. Agents.
B. What gets measured?
A. Concanavalin A, phytohemagglutinin.
B. The uptake of tritiated thymidine.
Tests of NK-cell function.
Chromium-release assays.
Colorimetric detection of granzyme B.
Nitroblue tetrazolium test: Principle.
A neutrophil capable of generating a normal oxidative burst will reduce yellow NBT to purple-blue formazan.
Nitroblue tetrazolium test: Interpretation.
~100% of neutrophils are F+: Normal.
<10%: Chronic granulomatous disease.
Use of flow cytometry to test for oxidative burst in neutrophils.
Oxidation of dihydrorhodamine 123 produces fluorescence that can be measured.
CH50 test:
A. Purpose.
B. Method.
C. Reported value.
A. To assess function of the classic pathway.
B. One determines the dilution of the patient’s serum that lyses 50% of immunoglobulin-coated sheep erythrocytes.
C. The reciprocal of the dilution.
Causes of deceased C3.
Primary deficiency of C3.
Activation of the alternative pathway.
Complement components measured in assessing the function of the classic pathway.
C4, C1q.
Uses of the complement-dependent-cytotoxicity assay (3).
Detecting HLA antigens or antibodies to them.
Performing HLA crossmatches.
Mixed lymphocyte culture: Purpose.
To detect differences in HLA class II antigens between a potential donor and a recipient.
Cross-reactive antigen group: Definition.
Group of HLA alleles for which there is serologic cross-reactivity.
Public antigen:
A. Definition.
B. Example.
A. A sequence of amino acids shared among many different HLA antigens.
B. HLA-Bw4, HLA-Bw6.
Public antigens: Significance.
In someone lacking a public antigen, sensitization can appear as many different HLA antibodies. This can complicate platelet transfusions and organ transplants.
Advantage of PCR in HLA typing.
Distinguishes among HLA types more precisely than does serology.
Panel-reactive-antibody tests:
A. Purpose.
B. Principle.
A. To help find a donor for a patient needing a transplant.
B. One determines the proportion of the donor population against which the patient’s HLA antibodies will react.
Panel-reactive-antibody tests: Reporting of results.
A PRA of 80% means that the patient has about a 20% chance of finding a compatible organ from an unrelated donor.
HLA matching for transplantation: Most important loci.
HLA-A, HLA-B, HLA-DR.
How to prevent hyperacute rejection.
Use the complement-dependent-cytotoxicity (CDC) assay to detect preformed antibodies against HLA antigens in the potential donor.
Advantages of flow cytometry in the crossmatching of transplants.
More sensitive than the CDC assay.
Detects lower titers of complement-dependent and complement-independent antibodies to the donor graft.
Correlation of Luminex technology with other techniques for crossmatching of transplants.
MFI (mean fluorescence intensity) . . .
> 5000: Correlates with incompatibility on flow cytometry of T and B cells.
> 10,000: Correlates with a positive CDC assay and the likelihood of hyperacute rejection.
Required compatibilities for transplantation of
A. Kidney.
B. Liver.
C. Heart.
D. Lung.
A. ABO, HLA, crossmatch.
B,C,D. Only ABO compatibility is required.
Required HLA compatibility for transplantation of allogeneic progenitor cells.
HLA-A, -B, -C, -DRB1.
Hyperacute rejection:
A. Onset.
B. Location of inciting antigens.
A. Within hours.
B. On the endothelium of the graft.
Hyperacute rejection: Histology.
Fibrin thrombi, platelet thrombi, necrosis, all due to complement-mediated vascular injury
Acute cellular rejection:
A. Onset.
B. Mechanism.
A. Evolves over days to weeks.
B. The recipient’s T cells recognize the donor’s HLA antigens as foreign and mount a powerful cytotoxic response.
Acute cellular rejection: Histology.
Lymphocytic infiltration of epithelium (tubulitis) and endothelium, along with interstitial edema.
Acute humoral rejection:
A. Onset.
B. Mechanism.
A. Within days or weeks.
B. Antibodies against the endothelium of the graft.
Acute humoral rejection: Histology (2).
Fibrinoid necrosis and neutrophilic infiltration of vessel walls, resulting in infarction.
- or -
Subendothelial intimal thickening with more protracted ischemia of the graft.
Acute humoral rejection: Patients at high risk.
Those who have been previously immunized against HLA antigens, due to pregnancy or transfusion.
Acute humoral rejection: Immunohistochemistry.
Demonstrates deposition of C4d in vessel walls.
Chronic rejection:
A. Onset.
B. Mechanism.
A. Develops over months or years.
B. Mediated by both lymphocytes and antibodies.
Chronic rejection: Histology.
Interstitial fibrosis, arteriolosclerosis, deposits of complement in peritubular vessels.
Graft-versus-host disease: Required conditions.
Immunocompetent T cells from the donor.
Immunosuppressed recipient.
Antigenic differences between donor and recipient.
Acute GVHD:
A. Onset.
B. Affected organs.
A. Within 100 days after transplant; usually within 30 days.
B. Skin, intestinal tract, hepatobiliary tract.
Acute GVHD: Effect on skin.
Red, itchy rash.
Histology: Apoptosis similar to that found in erythema multiforme.
Acute GVHD: Effect on intestinal tract.
Diarrhea.
Histology: Ectatic crypts with attenuated enterocytes, crypt abscesses, and apoptosis.
Acute GVHD: Effect on hepatobiliary tract.
Jaundice.
Histology: Mononuclear infiltrate in portal areas, with endothelialitis, ductitis, ductopenia.
Chronic GVHD:
A. Onset.
B. Affected organs.
A. >100 days after transplant.
B. Skin, intestinal tract, hepatobiliary tract; mucosa of mouth, vagina, eye, respiratory tract.
Chronic GVHD: Effect on
A. Skin.
B. Esophagus.
C. Eyes.
A. Extensive sclerosis.
B. Strictures.
C. Scarring lesions.
Bruton’s agammaglobulinemia:
A. Onset.
B. Infections.
C. Other complications.
A. Around 6 months of age.
B. Bacterial, enteroviral; viral hepatitis.
C. Lymphoid neoplasms, autoimmune diseases.
Bruton’s agammaglobulinemia: Laboratory findings.
Marked reduction in serum immunoglobulins.
Lack of CD19-positive B cells.
Bruton’s agammaglobulinemia: Physical examination.
Rudimentary lymph nodes and tonsils.
Bruton’s agammaglobulinemia: Gene and its location.
BTK on the X chromosome.
Common-variable immunodeficiency:
A. Onset.
B. Infections.
C. Other complications.
A. Second or third decade.
B. Recurrent infections of upper and lower respiratory tract; giardiasis.
C. Bronchiectasis, intestinal bacterial overgrowth.
Common-variable immunodeficiency: Laboratory findings.
Decreased serum immunoglobulins.
Variable T-cell deficiency.
Common-variable immunodeficiency: Histology.
Lack of plasma cells.
Reactive follicular hyperplasia; hyperplastic germinal centers.
Common-variable immunodeficiency: Underlying defect.
Excess of Th1 cells -> overproduction of IL-12 -> suppression of Th2 cells -> decreased stimulation of B cells to produce antibody.
Selective IgA deficiency:
A. Incidence.
B. Infections.
C. Other complications.
A. 1 in 700.
B. Respiratory and gastrointestinal; many patients have none.
C. Autoimmune disease; anaphylactic transfusion reaction.
Hyper-IgE syndrome: Clinical features.
Recurrent staphylococcal infections, coarse facial features, eczema, eosinophilia.
Hyper-IgE syndrome: Inheritance.
Autosomal dominant or autosomal recessive.
Immunodeficiencies with abnormal levels of IgE.
Increased: Hyper-IgE, Wiskott-Aldrich, Nezelof’s.
Decreased: Bruton’s, ataxia-telangiectasia.
DiGeorge’s syndrome: Embryological defect.
Failure of development of the 3rd and 4th pharyngeal pouches.
DiGeorge’s syndrome: Physical features.
Bifid uvula.
Anomalies of great vessels.
Typical facies.
Hypoplastic thymus and parathyroid.
Esophageal atresia.
CHARGE sequence.
A form of partial DiGeorge’s syndrome with
Coloboma. Heart defect. Atresia, choanal. Retarded development. Genital hypoplasia. Ear abnormalities.
DiGeorge’s syndrome:
A. Infections.
B. Other complications.
A. Opportunistic fungi, viruses, P. jiroveci.
B. Increased risk of transfusion-related GVHD.
DiGeorge’s syndrome: Histology.
Lymph nodes: Depleted paracortical regions.
Spleen: Poorly developed periarteriolar lymphatic sheaths.
DiGeorge’s syndrome:
A. Genetic basis.
B. Etiology.
A. Microdeletions involving 22q11.2.
B. Usually sporadic; some cases associated with isotretinoin.
Severe combined immunodeficiency: Affected parts of the immune system.
Function of T cells.
Immunoglobulin levels.
Thymus (dysplastic).
Severe combined immunodeficiency:
A. Clinical manifestations.
B. Genetic basis.
Life-threatening immunodeficiency.
Increased risk of transfusion-related GVHD.
Hyper-IgM syndrome: Clinical and laboratory findings.
Clinically similar to Bruton’s agammaglobulinemia.
Increased IgM; decrease in other immunoglobulins.
Hyper-IgM syndrome:
A. Molecular defect.
B. Inheritance.
A. Defect in CD154, the T-cell ligand for the B-cell receptor CD40.
B. X-linked.
Wiskott-Aldrich syndrome: Clinical triad.
Eczema, thrombocytopenia, immunodeficiency.
Wiskott-Aldrich syndrome:
A. Pathogens.
B. Gene.
A. Pneumococci and other encapsulated bacteria, Pneumocystis jiroveci, herpesviruses.
B. WAS gene on the X chromosome.
Ataxia-telangiectasia:
A. Sites of infection.
B. Other complication.
A. Upper and lower respiratory tract.
B. Various malignancies.
Ataxia-telangiectasia:
A. Affected parts of the immune system.
B. Laboratory abnormalities.
A. T cells and B cells.
B. Deficient IgA; very high serum AFP and CEA.
Ataxia-telangiectasia:
A. Inheritance.
B. Gene.
A. Autosomal recessive.
B. ATM gene on 11q23.3.
Chronic mucocutaneous candidiasis:
A. Affected part of the immune system.
B. Clinical associations.
A. T-cell function.
B. Endocrine dysfunction, autoimmune disorders.
Chronic mucocutaneous candidiasis: Gene.
Autoimmune-regulator gene (AIRE) on 21q22.3.
Duncan’s disease:
A. Type of immunodeficiency.
B. Pathogens.
C. Laboratory abnormalities.
A. Often similar to that of common-variable immunodeficiency.
B. Epstein-Barr virus can cause fulminant or fatal infection.
C. Inverted ratio of CD4 to CD8, hypogammaglobulinemia.
Duncan’s disease: Gene.
SH2D1A gene on Xq25 (encodes part of SLAM-associated protein).
Chronic granulomatous disease:
A. Most common enzymatic defect.
B. Pathogens.
C. Abnormalities of cell-surface antigens.
A. NADPH oxidase.
B. Staphylococci, enterobacters, Aspergillus.
C. Leukocytes lack C3bR; red cells often lack Kx.
Chédiak-Higashi syndrome:
A. Inheritance.
B. Gene.
A. Autosomal recessive.
B. CHS1/LYST (lysosomal trafficking regulator) on 1q42.1-2.
May-Hegglin anomaly:
A. Inheritance.
B. Peripheral smear.
A. Autosomal dominant.
B. Döhle-body-like inclusions that consist of RNA; variably sized platelets; thrombocytopenia.
Alder-Reilly anomaly:
A. Peripheral smear.
B. Clinical association.
A. Large azurophilic granules in all leukocytes.
B. Mucopolysaccharidoses.
Pelger-Huët anomaly:
A. Functional abnormality.
B. Inheritance.
C. Finding in homozygotes.
A. None.
B. Autosomal dominant.
C. Neutrophils with one nuclear lobe (Stodtmeister cells).
Jordan’s anomaly.
Fat vacuoles in neutrophils.
Deficiency in complement components that is associated with lupus.
C1q, C2, C4.
Deficiency in complement components that is associated with recurrent infections with Gram-positive organisms.
C2, C3.
Deficiency in complement components that is associated with serious systemic infections, esp. by neisseriae.
C5-C9.
Hereditary angioedema:
A. Inheritance.
B. Molecular basis.
A. Autosomal dominant.
B. Deficiency of the inhibitor of C1 esterase.
Hereditary angioedema: Laboratory findings (2).
During attacks: High urinary histamine, high serum C1; low serum CH50, C4, and C2.
Between attacks: Low serum C4, normal C2.
Hereditary angioedema: Therapy (3).
First-line: Recombinant C1-esterase inhibitor.
Second-line: Ecallantide (inhibits kallikrein), icatibant (blocks receptor of bradykinin B2).
Prophylaxis: Androgenic agents.
HLA type associated with
A. Hereditary hemochromatosis.
B. 21-hydroxylase deficiency.
C. Behçet’s disease.
A. A3.
B. C4.
C. B51.
HLA type associated with
A. Celiac disease.
B. Multiple sclerosis.
C. Diabetes mellitus, type 1.
A. DQ2, DQ8.
B. DRB1, DQB1.
C. DR3, DR4.
HLA type associated with
A. Narcolepsy.
B. Rheumatoid arthritis.
A. DQ6.
B. DR4.
Autoimmune disease that can result from infection by HBV.
Polyarteritis nodosa.
Associations between drugs and autoimmune diseases (5).
Methyldopa: Autoimmune hemolytic anemia.
Penicillamine: Systemic vasculitis.
Procainamide, hydralazine, isoniazid: Drug-induced lupus.
LE cell:
A. Definition.
B. Appearance.
A. A neutrophil that has ingested the nucleus of a lymphocyte.
B. The lymphocyte nucleus should appear pink and without discernible chromatin.
LE cell:
A. Locations (3).
B. Variant.
A. Pleural effusions, joint effusions, bone-marrow aspirates.
B. Tart cell: The lymphocyte nucleus appears blue-purple, with retained chromatin detail.
Direct immunofluorescence: Purpose and technique.
To look for autoantibodies that are already bound to the tissues.
Cryostat sections of patient’s tissue are incubated with fluorescein-labeled antihuman globulin.
Indirect immunofluorescence: Purpose and technique.
To look for circulating autoantibodies.
The patient’s serum is incubated with cells or tissues containing known antigens. Then fluorescein-labeled antihuman globulin is added.
ANA: How detected.
By means of indirect immunofluorescence with HEp-2 cells.
ANA: How measured.
The pattern of fluorescence is noted for mitotically active and inactive cells.
All positive samples are serially diluted to determine titer.
ANA with homogeneous staining: Antigens.
ssDNA, histones.
ANA with homogeneous staining: Diseases.
High titer: SLE.
Low titer: Sjögren’s syndrome, MCTD, RA.
ANA with peripheral (rim) staining: Antigens.
dsDNA (nuclear envelope).
ANA with peripheral (rim) staining: Diseases.
Primary biliary cirrhosis, chronic liver disease, drug-induced lupus.
ANA with homogeneous or peripheral (rim) staining: How to distinguish from a speckled pattern.
In the speckled pattern of ANA, the mitotic figures are not stained.
ANA with speckled pattern: Antigens.
Extractable nuclear antigens: Sm, RNP, Scl-70, Ro/SS-A, La/SS-B, PCNA.
ANA with speckled pattern: Diseases.
CREST syndrome, scleroderma, SLE, MCTD, Sjögren’s syndrome, rheumatoid arthritis.
ANA with nucleolar pattern: Antigens.
RNA polymerase I, small RNPs, Th/To, B23, PM-Scl, NOR-90.
ANA with nucleolar pattern: Diseases.
Scleroderma, polymyositis/scleroderma.
ANA with centriolar pattern: Antigens.
CENP-A, -B, and -C.
ANA with centriolar pattern: Diseases.
CREST syndrome, idiopathic Raynaud’s phenomenon.
ANA: Specificity for lupus (2).
80% at a titer of 1 : 40.
95% at a titer of 1 : 160.
How indirect immunofluorescence is used to test for antibodies to double-stranded DNA.
The kinetoplast of Crithidia luciliae contains double-stranded DNA.
Systemic lupus erythematosus: Most important diagnostic tests (4).
ANA.
Antibodies against Sm, dsDNA, phospholipids.
Antibodies to RNP: Disease.
MCTD if of high titer (1 : 10,000) and in isolation.
Ro and La antibodies:
A. Synonyms.
B. Disease.
Sjögren’s syndrome, if there are no antibodies against dsDNA or Sm.
Antibodies to Scl-70: Disease.
Progressive systemic sclerosis.
Antibodies to centromeres: Diseases.
CREST syndrome.
Occasionally seen in progressive systemic sclerosis and Raynaud’s phenomenon.
Signal-recognition particles:
A. Examples.
B. Antibodies are associated with what disease?
A. Jo-1, PM/Scl.
B. Inflammatory myositis.
Screening for antibodies to cytoplasmic antigens: Substrate.
Rat tissue: Liver, kidney, and stomach.
Antimitochondrial antibodies:
A. Reactivity.
B. Specificity.
A. Gastric parietal cells, renal tubular cells, hepatocytes.
B. M2 antigen.
Anti-smooth-muscle antibody: Reactivity.
Smooth muscle of gastric tissue and renal arterioles.
Anti-liver-kidney-microsomal antibody: Reactivity.
Hepatocytes, renal tubular cells.
Antineutrophil-cytoplasmic antibodies: Procedure (2).
The patient’s serum is incubated with alcohol-fixed neutrophils.
All positive samples are tested for ANA in order to exclude a false-positive ANCA.
Cytoplasmic ANCA:
A. Pattern.
B. Specificity.
C. Disease.
A. Cytoplasmic granular pattern with perinuclear accentuation.
B. Proteinase 3.
C. Wegener’s granulomatosis.
Perinuclear ANCA:
A. Pattern.
B. Specificity.
C. Diseases (4).
A. Mostly perinuclear.
B. Myeloperoxidase.
C. Microscopic polyangiitis, polyarteritis nodosa, PSC, ulcerative colitis.
Technique other than immunofluorescence that is being used to identify autoantibodies in tissues.
Enzymatic immunoassay (EIA).
Anti-Jo1:
A. Synonym.
B. Disease.
A. Anti-tRNA synthetase.
B. Polymyositis, especially with pulmonary fibrosis.
Antihistone antibodies: Disease.
Drug-induced lupus.
Antibodies to extractable nuclear antigens: Substrate for testing.
Calf thymus.
Anti-RNP antibodies: Disease.
Mixed connective-tissue disease.
Antinucleolar antibodies: Disease.
Scleroderma.
Antibodies to SS-A and SS-B: Diseases (3).
Sjögren’s syndrome,
Neonatal lupus.
Lupus nephritis – if ANA and anti-SS-A are positive but anti-SS-B is negative.
Antimicrosomal antibodies: Disease.
Highly specific and sensitive for Hashimoto’s thyroiditis.
Present in up to half of patient’s with Grave’s disease.
Antibodies to the glomerular basement membrane:
A. Specificity.
B. Disease.
A. Type IV collagen.
B. Goodpasture’s syndrome.
Antibodies to intermediate filaments: Disease.
Polymyositis/dermatomyositis.
Antibody to RNA polymerase: Disease.
Scleroderma.
Antiribosomal P antibodies: Disease.
Polymyositis/dermatomyositis.
Antibody to topoisomerase:
A. Disease.
B. Synonym.
A. Scleroderma.
B. Anti-Scl-70.
Anti-U1-RNP:
A. Disease.
B. Synonym.
A. Progressive systemic sclerosis.
B. Anti-fibrillarin.
Utility of test for antibodies to cyclic citrullinated peptides.
More specific and more sensitivity than rheumatoid factor.
Causes of elevated angiotensin-converting enzyme (4).
Sarcoidosis.
Primary biliary cirrhosis.
Gaucher’s disease.
Leprosy.
SLE: Findings that occur in more than half of patients.
Rash.
Arthralgia.
Neurological disease.
Serositis.
Hematological disease.
SLE: Criteria of the American College of Rheumatology.
Malar rash, discoid rash, photosensitivity. Oral ulcers. Arthritis, serositis. Renal dysfunction. Neurological dysfunction. Hematological disorder. Autoantibodies. Antinuclear antibody.
SLE: Most common autoantibodies (6).
ANA.
Anti-dsDNA.
Anti-ssDNA.
Anti-SS-A, anti-SS-B.
Anti-Sm.
Drug-induced lupus: Drugs.
Procainamide.
Hydralazine.
Quinidine.
Isoniazid.
IFN-α.
Drug-induced lupus: Specificity of antibody.
H2A-H2B complex.
Rheumatoid arthritis: Hematological findings.
Anemia of chronic disease.
Thrombocytosis.
Rheumatoid arthritis: How many have a rheumatoid factor?
Most, but up to 30% have none initially.
Rheumatoid arthritis: Synovial fluid.
Pleocytosis, mostly neutrophils.
Decreased glucose.
The seronegative spondyloarthropathies.
Ankylosing spondylitis.
Psoriatic arthritis.
Reactive arthritis.
Reactive arthritis: Pathogens.
Chlamydia.
Shigella, Salmonella, Yersinia, Campylobacter.
Celiac disease: Associated diseases of autoimmunity.
Diabetes mellitus, type 1.
Autoimmune liver disease.
Celiac disease: Associated non-immunological diseases.
IgA deficiency.
Cystic fibrosis.
Turner’s syndrome.
Down’s syndrome.
Celiac disease: Possible nutrient deficiencies.
Iron, folate.
Celiac disease: Extraintestinal manifestations.
Dermatitis herpetiformis.
Arthritis.
Progressive systemic sclerosis:
A. Synonym.
B. Leading causes of death.
A. Scleroderma.
B. Pulmonary hypertension, renal crisis.
IgG4-related systemic sclerosis: Manifestations (6).
Sclerosing mediastinitis. Sclerosing pancreatitis. Sclerosing cholangitis. Riedel's thyroiditis. Idiopathic retroperitoneal fibrosis. Orbital pseudotumor.
IgG4-related systemic sclerosis:
A. Histology.
B. Other test.
A. Infiltrate of IgG4-producing plasma cells.
B. Serum IgG4.
Autoimmune hepatitis: Types and their antibodies.
Type 1: ANA, anti-smooth-muscle, anti-soluble liver protein.
Type 2: Anti-liver-kidney-microsomal, anti-CYP 2D6.
Progressive systemic sclerosis: Types (3).
Diffuse-cutaneous: Involves skin and viscera.
Limited-cutaneous: Like D-C but less severe.
Localized: Limited to skin.
Primary biliary cirrhosis: Antibodies.
Antimitochrondrial.
IgG anti-sp100.
IgG anti-gp210.
Primary biliary cirrhosis: Non-immunological laboratory abnormality.
Hypercholesterolemia.
Elevated immunoglobulin in
A. Autoimmune hepatitis.
B. Primary biliary cirrhosis.
A. IgG.
B. IgM.
Rheumatoid arthritis: Extraarticular manifestations (4).
Interstitial lung disease.
Pleuritis.
Endocarditis.
Systemic vasculitis.
Sjögren’s syndrome: Associations (4).
Rheumatoid arthritis.
Primary biliary cirrhosis.
SLE.
Systemic sclerosis.
Sjögren’s syndrome: Histologic diagnosis.
Biopsy of minor salivary gland showing >1 inflammatory focus per 4 mm².
A “focus” is an aggregate of at least 50 mononuclear inflammatory cells.
Vasculitides having no serologic markers (6).
Giant-cell arteritis. Takayasu's arteritis. Kawasaki syndrome. Cogan's syndrome. Behçet's disease. Buerger's disease.
Vasculitides with pANCA (2).
Microscopic polyangiitis.
Churg-Strauss syndrome.
Vasculitis with cANCA.
Wegener’s granulomatosis.
Immunoglobulin light chains: Domains.
One variable domain and one constant domain.
Kawasaki’s disease:
A. Age at onset.
B. Mortality.
A. 2 or 3 years.
B. 1-2% of untreated cases; death results from coronary-artery disease.
Serologic marker: Polyarteritis nodosa.
Some patients are HBV positive; otherwise no markers.
Kawasaki’s disease:
A. When does the desquamation occur?
B. Other clinical features (4).
A. After 5 days of fever.
B. Bilateral conjunctivitis, cracking of lips, strawberry tongue, cervical lymphadenopathy.
Henoch-Schönlein purpura: Renal biopsy.
Findings similar to those of IgA nephropathy.
Cogan’s syndrome: Clinical manifestations.
Keratitis.
Vestibulo-auditory symptoms.
Henoch-Schönlein purpura: Clinical features (3).
Palpable purpura on lower extremities.
Abdominal pain.
Glomerulonephritis.
Polyarteritis nodosa: Affected organs.
Many, but the lungs are spared.
Polyarteritis nodosa: Neurological manifestation.
Mononeuritis complex.
Polyarteritis nodosa: Histology.
Segmental fibrinoid necrosis of inflamed arterial walls, especially at branch points.
Active and healing lesions are seen in the same biopsy.
Microscopic polyangiitis:
A. Involved organs.
B. Involved vessels.
A. Many, but especially lungs and kidneys.
B. Small arterioles and venules.
Microscopic polyangiitis:
A. Typical renal lesion.
B. Serologic marker.
A. Focal-segmental necrotizing glomerulonephritis, pauci-immune type.
B. pANCA.
Chung-Strauss syndrome: Clinical presentation.
Asthma of adult onset; progression to fulminant vasculitis.
Churg-Strauss syndrome: Main cause of death.
Cardiac disease.
Churg-Strauss syndrome: Laboratory findings.
Peripheral eosinophilia.
pANCA.
Behçet’s disease: Classic triad.
Oral aphthous ulcers.
Genital aphthous ulcers.
Uveitis.
Behçet’s disease: Unique test.
Pathergy test: One looks for development of erythema, induration, and pustule at the site of a needle stick.
Giant-cell arteritis: Association.
Polymyalgia rheumatica.
Dermatomyositis/polymyositis: Typical serologic markers (3).
Anti-Jo1, anti-SRP, anti-PM/Scl.
Inclusion-body myositis:
A. Incidence.
B. Diagnosis.
A. Most common inflammatory myopathy in older adults.
B. Muscle biopsy. No specific serologic markers.
Myasthenia gravis: Antibody and its sensitivity and specificity.
Antibody to the acetylcholine receptor.
75-95% sensitive.
~100% specific.
Myasthenia gravis: Types in which anti-titin antibodies are found.
Late-onset.
Thymoma-associated.
Myasthenia gravis: Types in which anti-MuSK antibodies are found.
Seronegative.
Familial Mediterranean fever:
A. Inheritance.
B. Gene and its location.
C. Affected protein.
A. Autosomal recessive.
B. MEFV on chromosome 16.
C. Pyrin (marenostrin).
Familial Mediterranean fever:
A. Symptoms.
B. Complication.
A. Fever; pain from serositis.
B. Renal amyloidosis (AA).
Type I hypersensitivity:
A. Synonym.
B. Mechanism.
A. Immediate.
B. IgE-mediated release of histamine, serotonin, and other substances from mast cells.
Diagnosis of anaphylaxis:
A. Use of tryptase.
B. Use of histamine.
A. Mature serum tryptase better reflects mast-cell degranulation than does total tryptase.
B. Plasma histamine peaks earlier than tryptase and returns to normal in 1 hour. Urine tryptase may remain elevated for 24 hours.
Type II hypersensitivity:
A. Synonym.
B. Mechanism.
A. Antibody-mediated cellular cytotoxicity.
B. Formation of antibody-antigen complexes, opsonization.
Type II hypersensitivity: Examples.
Goodpasture’s syndrome, myasthenia gravis, immune-mediated hemolysis.
Takayasu’s arteritis:
A. Histology.
B. Distinction from giant-cell arteritis.
A. Infiltration of arterial wall by mononuclear inflammatory cells and multinucleate giant cells.
B. Takayasu’s arteritis affects patients under 40.
Type IV hypersensitivity: Mechanism.
Response of T cells to antigen, usually with granulomatous inflammation.
Type III hypersensitivity:
A. Mechanism.
B. Examples.
A. Formation of antibody-antigen complexes, activation of complement.
B. Serum sickness, Henoch-Schönlein purpura.
Wegener’s granulomatosis: Typical renal lesion.
Focal-segmental necrotizing glomerulonephritis, pauci-immune type.
Takayasu’s arteritis: Possible clinical mimic.
Syphilitic arteritis.
