Step 1 - Immuno 2

denniskwinn's version from 2015-04-25 16:04


Question Answer
Type I hypersensitivityAnaphylactic and atopic - free antigen crosslinks IgE on presensitized mast cells and basophils triggering release of vasoactive amines that act at postcapillary venules (i.e. Histamine). Reaction develops rapidly after antigen exposure due to preformed antibody.
Type I hypersensitivity testscratch test and radioimmunosorbent assay
Type II hypersensitivityIgM, IgG bind to fixed antigen on “enemy” cell, leading to lysis (by complement) or phagocytes. 3 mechanisms: 1. Opsonize cells or activate complement 2. Antibodies recruit neutrophils and macrophages that incite tissue damage 3. Bind to normal cellular receptors and interfere with functioning. . . Antibody and complement lead to MAC. . .
Type II hypersensitivity testdirect and indirect coombs
Type III hypersensitivity1. Immune complex (antigen-antibody-complement) attracts nphils, and enzymes. . 2. Serum sickness - antibodies to foreign proteins form (5 days). Immune complexes form and deposit in membranes where they fix complement - more common than arthus rxn 3. Arthus rxn - local subacute rxn - intradermal injection of antigen induces antibodies, which from antigen-antibody complexes in skin - edema, necrosis, complement activation
Type III hypersensitivty testimmunofluorescent staining
Type IV hypersensitivityDelayed (T cell mediated) - sesitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no antibody involved) - 4Ts, T lymphocytes, Transplant rejection, TB skin tests, Touching (contact dermatitis)
Type IV hypersensitivity testpatch test (e.g. PPD)
Type I hypersensitivity disorders1. Anaphylaxis (bee sting, some food/drug allergies) 2. Allergic and atopic disorders (e.g. Rhinitis, hay fever, eczema, hives, asthma)
Type I hypersensitivity presentationImmediate, anaphylactic, atopic
Type II hypersensitivity disorders1. Hemolytic anemia, 2. Pernicious anemia 3. ITP 4. Erythroblastosis fetalis 5. Acute hemolytic transfusion rxns 6. Rheumatic fever 7. Goodpasture’s syndrome 8. Bullous pemphigoid 9. Pemphigus vulgaris 10. Grave’s disease 11. Myasthenia gravis
Type II hypersensitivity presentationtend to be specific to tissue or site where antigen is found
Type III hypersensitivity disordersSLE, RA, Polyarteritis nodosa, Poststrep glomerulonephritis, Serum sickness, Arthus rxn (swelling and inflammation following tetanus vaccine), Hypersensitivity pneumonitis (farmer’s lung)
Type III hypersensitivity presentationcan be associated with vasculitis and systemic manifestations
Type IV hypersensitivity disordersType I DM, MS, Guillain-Barre syndrome, Hashimoto’s thyroiditis, GVHD, PPD, Contact dermatitis (poison ivy)
Type IV hypersensitivy presentationResponse is delayed and does not involve antibodies


Question Answer
Antinuclear antibodies (ANA) inSLE
Anti-dsDNA, anti-Smith antibodies inSLE - specific for SLE
Antihistone antibodies inDrug-induced lupus
Anti-IgG (RF) inRheumatoid arthritis
Anticentromere antibodiesScleroderma (CREST)
Anti-Scl-70 (anti-DNA topoisomerase I)Scleroderma (diffuse)
Antimitochondrial antibodiesPrimary biliary cirrhosis
Antigliadin, antiendomysial antibodiesCeliac disease
Anti-basement membrane antibodiesGoodpasture’s syndrome
Anti-desmoglein antibodiesPemphigus vulgaris
Antimicrosomal, antithyroglobulin antibodiesHashimoto’s thyroiditis
Anti-Jo-1 antibodiesPolymyositis, dermatomyositis
Anti-SS-A (anti-Ro)Sjogren’s syndrome
Anti-SS-B (anti-La)Sjogren’s syndrome
Anti-UI RNP (ribonucleoprotein)Mixed connective tissue disease
Anti-smooth muscle antibodies Autoimmune hepatitis
Anti-glutamate decarboxylase antibodiesType I diabetes mellitus
C-ANCA antibodiesWegener’s granulomatosis
P-ANCA antibodiesOther vasculitidies


Question Answer
Bruton's agammaglobulinemia DefectX-Linked recessive (↑ in Boys) Defect in BTK, ,a tyrosine kinase gene → blocks B-ce11 differentiation/maturation .
Bruton's agammaglobulinemia PresentationRecurrent bacterial infections after 6 months (↓ maternal IgG) due to opsonization defect
Bruton's agammaglobulinemia LabsNormal pro-B, ↓ maturation, ↓ number of B cells, ↓ immunoglobulins of all classes
Hyper-lgM syndrome DefectDefective CD40L on helper T cells = inability to class switch
Hyper-lgM syndrome Presentationsevere pyogenic infections early in life
Hyper-lgM syndrome Labs↑ IgM, ↓↓IgG, IgA, IgE
Selective Ig deficiency DefectDefect in isotype switching → deficiency in specific class of immunoglobulins
Selective Ig deficiency PresentationSinus and lung infections, milk allergies and diarrhea. Anaphylaxis on exposure to blood products with IgA
Selective Ig deficiency LabsIgA deficiency most common - Failure to mature into plasma cells (↓ secretory IgA)
Common variable immunodeficiency (CVlD) DefectDefect in B-cell maturation; many causes
Common variable immunodeficiency (CVlD) PresentationCan be acquired in 20s-30s, ↑ risk of autoimmune disease, lymphoma, sinopulmonary infections
Common variable immunodeficiency (CVlD) LabsNormal number of B cells, ↓ plasma cells, immunoglobulin
Thymic aplasia (DiGeorge syndrome) Defect22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches
Thymic aplasia (DiGeorge syndrome) PresentationTetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), congenital heart and great vessel defects
Thymic aplasia (DiGeorge syndrome) LabsThymus and parathyroids fail to develop → ↓T cells, ↓PTH, ↓Ca2+. . Absent thymic shadow on CXR
IL-12 receptor deficiency Defect↓ Th1 response
IL-12 receptor deficiency PresentationDisseminated mycobacterial infections
IL-12 receptor deficiency Labs↓ IFN gamma
Hyper IgE syndrome (Job’s syndrome) DefectTh cells fail to produce IFN-gamma → inability of neutrophila to respond to chemotactic stimuli
Hyper IgE syndrome (Job’s syndrome) PresentationFATED: coarse Facies, cold (noninflamed) staphylococcal, Abscesses, retained primary Teeth, ↑ IgE, Dermatologic problems (eczema)
Hyper IgE syndrome (Job’s syndrome) Labs↑IgE
Chronic mucocutaneous candidiasis DefectT-cell dysfunction
Chronic mucocutaneous candidiasis PresentationCandida albicans infections of skin and mucous membranes
Severe combined immunodeficiency (SCID) DefectSeveral types: defective IL-2 receptor (most common, X-linked), adenosine deaminase deficiency, failure to synthesize MHC II antigens
Severe combined immunodeficiency (SCID) PresentationRecurrent viral, bacterial, fungal and protozoal infections due to both B and T cell deficiency, chronic diarrhea, failure to thrive
SCID treatmentbone marrow transplant (no allograft rejection)
Severe combined immunodeficiency (SCID) Labs↓ IL-2R = ↓ T-cell activation, ↑ adenin = toxic to B and T cells (dNTPs, ↓DNA synthesis)
Ataxia-telangiectasia DefectDefect in DNA repair enzymes
Ataxia-telangiectasia PresentationTriad of cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA deficiency
Ataxia-telangiectasia LabsIgA deficiency
Wiskott-Aldrich sydrome DefectX-linked recessive defect, T cells unable to reorganize actin cytoskeleton
Wiskott-Aldrich sydrome PresentationTriad (TIE) - Thrombocytopenic purpura, Infections, Eczema
Wiskott-Aldrich sydrome Labs↑ IgE, IgA, ↓IgM
Leukocyte adhesion deficiency (type I) DefectDefect in LFA-1 integrin (CD18) protein on phagocytes
Leukocyte adhesion deficiency (type I) PresentationRecurrent bacterial infections, absent pus formation, delayed separation of umbilicus
Leukocyte adhesion deficiency (type I) LabsNeutrophilia
Chediak-Higashi syndrome DefectAutosomal recessive defect in microtubular function with ↓ phagosome-lysosome fusion
Chediak-Higashi syndrome PresentationRecurrent pyogenic infections by staphylococci and streptococci; partial albinism, peripheral neuropathy
Chronic granulomatous disease DefectLack of NADPH oxidase → ↓ reactive oxygen species (e.g. Superoxide) and absent respiratory burst in neutrophils
Chronic granulomatous disease Presentation↑ susceptibility to catalase-positive organisms (S.aureus, E.coli, Aspergillis)
Chronic granulomatous disease LabsNegative nitroblue tetrazolium dye reduction test
Draw picture of sites of block of Lymphocyte developmentdraw
AutograftFrom self
Syngeneic graftfrom identical twin or clone
AllograftFrom nonidentical individual of same species
Xenograftfrom different species


Question Answer
Hyperacute rejectionAntibody mediated (type II) due to the presence of preformed antidonor antibodies in the transplant recipient. Occurs within minutes after transplantation
Acute rejectionCell mediated due to cytotoxic T lymphocytes reacting against foreign MHCs. Occurs weeks after transplantation. Reversible with immunosuppressants such as cyclosporine and OKT3
Chronic rejectionT cell and antibody mediated vascular damage (obliterative vascular fibrosis); occurs months to years after transplantation. Irreversible. Class I-MHC (non-self) is perceived by CTLs as class I MHC(self) presenting a non-self antigen
Graft-versus-host-diseaseGrafted immunocompetent T cells proliferate in the irradiated immunocompromised host and reject cells with “foreign” proteins, resulting in severe organ dysfunction. Major symptoms include a macopapular rash, jaundice, hepatosplenomegaly and diarrhea


Question Answer
Cyclosporine clinical useSupresses organ rejection after transplantation; selected autoimmune disorders
Cyclosporine ToxicityPredisposes patients to viral infections and lymphoma; nephrotoxic (preventable with mannitol diuresis)
Tacrolimus (FK506) clinical usePotent immunosuppressive used in organ transplant recipients
Tacrolimus (FK506) ToxicitySignificant - nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia
Azathioprine Clinical useKidney transplantation, autoimmune disorders (including glomerulonephritis and hemolytic anemia)
Azathioprine ToxicityBone marrow suppression. Active metabolite mercaptopurine is metabolized by xanthine oxidase; thus, toxic effects may be ↑ by allopurinol
Muromonab-CD3 (OKT3) clinical useImmunosuppression after kidney transplantation
Muromonab-CD3 (OKT3) toxicityCytokine release syndrome, hypersensitivity reaction
Sirolimus (rapamycin) clinical useImmunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids
Sirolimus (rapamycin) toxicityHyperlipidemia, thrombocytopenia, leukopenia
Daclizumab mechanismMonoclonal antibody with high affinity for IL-2 receptor on activated T cells
Aldesleukin (IL2) clinical useRenal cell carcinoma, metastatic melanoma
Erythropoietin (epoetin) clinical useAnemias (especially in renal failure)
Filgrastim (granulocyte colony-stimulating factor) clinical useRecovery of bone marrow
Sargramostim (granulocyte-macrophage colony stimulating factor) clinical useRecovery of bone marrow
Alpha interferon clinical useHep B, C, Kaposi’s sarcoma, leukemias, malignant melanoma
Beta interferon clinical usemultiple sclerosis
Gamma interferon clinical useChronic granulomatous disease
Oprelvekin (interleukin-11) clinical useThrombocytopenia
Thrombopoietin clinical useThrombocytopenia

CD markers

Cd1Class I MHC-like, nonpeptide antigen presentationDCs, Mphages
CD2 (LFA-3R)RBC receptorT cells
Cd3TCR subunit (γ, δ, ω, ζ, η); activationT cells
Cd4Class II MHC receptorT cell subset, monocytes, some DCs
Cd8Class I MHC receptorT cell subset, some DCs
Cd14LPS-binding proteinMyeloid cells (DCs, monocytes, Mphages)
CD21 (CR2)C3d complement receptor, EBV receptor, B cell activationB cells
Cd25IL-2 receptor (α chain), early activation marker, marker for regulatory cellsActivated T cells, regulatory T cells
Cd28Receptor for B-7 costim: activationT cells
Cd40Stim of B cells, DCs,&MphagesB cells, Mphages
CD40 LLigand for CD40T cells
CD80 (B7-1)Costim of T cells on APCsDC, Mphages, B cells
CD86 (B7-2)Costim of T cells on APCsDC, Mphages, B cells
CD95 (Fas)Apop inducerMany cells
CD152 (CTLA-4)Receptor for B-7; toleranceT cells
CD178 (FasL)Fas ligand: apop inducerKiller T&NK cells
Adhesion Molecules
Cd11aLFA-1 (α chain)
 Cd29VLA (β chain)
 VLA-1, VLA-2, VLA-3α IntegrinsT cells
VLA-4α4-Integrin homing receptorT cells, B cells, monocytes