Immunology - Part 2

shaile's version from 2015-06-06 21:14

Hypersensitivity Types

Question Answer
All 4 typesACID
Type 1: anaphylactic and atopic
Type 2: Cytotoxic
Type 3: Immune complex
Type 4: Delayed (T-cell-mediated) type
Which type does not involve antibodies?Type 4
Examples of Type 4T's
Transplant rejections
TB skin tests
Touching (contact dermatitis)
Serum sickness mechanismImmune complex disease (type 3)
Antibodies to the forein proteins are produced (takes 5 days)
Immune complexes form → deposited in membranes → fix complement → tissue damage
Arthus reactionlocal subacute antibody-mediated hypersensitivity (type 3)
Intradermal injection of antigen → induces antibodies → form antigen-antibody complex in the skin
Edema, necrosis, and activation of complement
Test for Type 1skin test specific for IgE
Test for Type 2direct or indirect Coombs'
Example of Type 2penicillin binds to RBCs → Recognized by body as foreign → B cells proliferate producing IgM and IgG that take out the cell (RBC in this case)
Serum sickness presentationFever, urticaria, arthralgias, proteinuria, lymphadenopathy
5-10 days after antigen exposure
Test for Type 3Immunofluorescent staining
Test for Type 4Patch test, PPD
Type 1 presentationImmediate, anaphylactic, atopic (may occur in part of the body that's not in contact with the allergen)
Type 2 presentationDisease tends to be specific to tissue or site where antigen is found
Type 3 presentationCan be associated with vasculitis and systemic manifestations
Type 4 presentationResponse is delayed and does not involve antibodies

Rapid-fire Hypersensitivity disorders

Question Answer
Anaphylaxis (bee sting, some food/drug allergies)Type 1
Allergic and atopic disorders (rhinitis, hay fever, eczema, hives, asthma)Type 1
Autoimmune hemolytic anemiaType 2
Pernicious anemiaType 2
Idiopathic thrombocytopenic purpuraType 2
Erythroblastosis fetalisType 2
Acute hemolytic transfusion reactionsType 2
Rheumatic feverType 2
Goodpasture's syndromeType 2
Bullous pemphigoidType 2
Pemphigus vulgarisType 2
SLEType 3
Polyarteritis nodosaType 3
Poststreptococcal glomerulonephritisType 3
Serum sicknessType 3
Arthus reaction (swelling & inflammation following a vaccine)Type 3
Multiple sclerosisType 4
Guillain-Barre syndromeType 4
Graft-versus-host diseaseType 4
PPDType 4
Contact dermatitisType 4
Allergic reaction to blood transfusionType 1
Anaphylactic reaction to blood transfusionType 1
Febrile nonhemolytic (blood) transfusion reactionType 2 - against donor HLA antigens and leukocytes
Acute hemolytic (blood) transfusion reactionType 2 - intravascular - ABO blood group incompatibility - causes hemoglobinemia
extravascular - foreign antigen on donor RBCs - causes jaundice

Rapid-fire autoantibodies

Question Answer
ANASLE, nonspecific
Anti-dsDNA, anti-SmithSLE
AntihistoneDrug-induced lupus
Rheumatoid factorRheumatoid arthritis
anti-CCPRheumatoid arthritis
AnticentromereScleroderma (CREST syndrome)
Anti-Scl-70 (anti-DNA topoisomerase I)Scleroderma (diffuse)
Antimitochondrial1° biliary cirrhosis
IgA antiendomysial, IgA anti-tissue transglutaminaseCeliac disease
Anti-basement membraneGoodpasture's syndrome
Anti-desmogleinpemphigus vulgaris
AntimicrosomalHashimoto's thyroiditis
antithyroglobulinHashimoto's thyroiditis
Anti-Jo-1, anti-SRP, anti-Mi-2Polymyositis, dermatomyositis
Anti-SSA (anti-Ro)Sjogren's syndrome
Anti-SSB (anti-La)Sjogren's syndrome
Anti-U1 RNP (ribonucleoprotein)Mixed connective tissue disease
Anti-smooth muscleAutoimmune hepatitis
Anti-glutamate decarboxylaseType 1 DM
c-ANCA (PR3-ANCA)Granulomatosis with polyangiitis (Wegener's)
p-ANCA (MPA-ANCA)Microscopic polyangiitis, Churg-Strauss syndrome

Infections in immunodeficiency

Question Answer
No T cells - bacterial infectionsSepsis
No T cells - viral infectionsCMV, EBV, VZV
chronic infection with respiratory/GI virus
No T cells - Fungi/parasite infxnsCandida
No B cells - bacterial infectionsSHiN SKiS: Streptococcus pneumoniae, H. influenzae type B, Neisseria meningitidis, Salmonella, Klebsiella pneumoniae, group B Strep
No B cells - Viral infxnsEnteroviral encephalitis
poliovirus (live vaccine is contraindicated)
No B cells - fungal/parasite infxnsGI giardiasis (no IgA)
No granulocyte - bacteria infxnsStaphylococcus
Burkholderia cepacia
No granulocyte - viral infxnN/A
No granulocyte - fungal infxnCandida
No complement - Bacterial infxnNeisseria (no MAC)
Major trendB-cell deficiencies produce more recurrent bacterial infections
T-cell deficiencies produce more fungal and viral infections

Immune deficiencies

Question Answer
Recurrent bacterial infections after 6 monthsX-linked (Bruton's) agammaglobulinemia
XR - more common in boys
No B-cell maturation d/t defect in BTK, a tyrosine kinase gene
↓ # of B cells
↓ immunoglobulins of all classes
Mostly asymptomatic. Can see sinopulmonary infxns
GI infxns
autoimmune disease
Anaphylaxis to blood transfusion
Selective IgA deficiency
IgA<7 mg/dL
False-positive B-HCG test
20-30 y/o
autoimmune diseases
sinopulmonary infections
Common variable immunodeficiency (CVID)
defect in B-cell maturation - but normal # of B cells
↓ plasma cells
↓ immunoglobulins
Tetany (hypocalcemia)
Recurrent viral/fungal infections (T-cell deficiency)
congenital heart and great vessel defects
Thymic aplasia (DiGeorge syndrome)
22q11 deletion; failure of 3rd/4th pharyngeal pouches
↓ T cells, ↓ PTH, ↓ Ca
Disseminated mycobacterial (TB) infectionsIL-12 receptor deficiency
↓ Th1 response
↓ IFN-gamma
Course facies
Cold (noninflamed) staphylococcal abscesses
Retained primary Teeth
↑ IgE
Dermatologic problems (eczema)
Hyper-IgE syndrome (Job's syndrome)
Th1 cells fail to produce IFN-gamma → inability of neutrophils to respond to chemotactic stimuli
↑ IgE
Candida albicans infections of skin and mucous membranesChronic mucocutaneous candidiasis
T cell dysfn
Failure to thrive
chronic diarrhea
recurrent infections of all kinds
Severe combined immunodeficiency (SCID)
2 causes: defective IL-2 receptor (X-linked), adenosine deaminase deficiency
Findings: No thymic shadows, no germinal centers in LN biopsy, no B cells
↓ T-cell recombinant excision circles
Tx: bone marrow transplant
Cerebellar defects
spider angiomas
IgA deficiency
Defects in the ATM gene which codes for DNA repair enzymes
Severe pyogenic infections early in lifeHyper-IgM syndrome
Defective CD40L on helper T cells → inability to class switch
↑ IgM
↓↓ IgG, IgA, IgE
TIE: Thrombocytopenic purpura
Wiskott-Aldrich syndrome
X-linked, T cells unable to recognize actin cytoskeleton
↑ IgE, IgA
↓ IgM
Recurrent bacterial infxns
absent pus formation
delayed umbilical cord separation
Leukocyte adhesion deficiency (type 1)
Defect in LFA-1 integrin (CD18) protein on phagocytes
Recurrent pyogenic infections by staph and strep
Partial albinism
peripheral neuropathy
Chediak-Higashi syndrome
AR - microtubule dysfunction in phagosome-lysosome fusion
Giant granules in neutrophils
↑ susceptibility to catalase-positive organisms
(Staph aureus, E.coli, Aspergillus)
Chronic granulomatous disease
Lack of NADPH oxidase
Abnormal dihydrorhodamine flow cytometry test


Question Answer
Autograftfrom self
Syngeneic graftFrom identical twin or clone
AllograftFrom another person
Xenograftfrom different species
Hyperacute rejectionsImmediate occlusion of graft vessels → ischemia and necrosis
Acute rejectionWeeks later
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrates
Reaction to forein MHCs - can reverse with immunosuppressants
Chronic rejectionObliterative vascular fibrosis - months to years later
Class I-MHCnon-self perceived by CTLs as class I-MHCself presenting a non-self antigen
Graft-versus-host rejectionMaculopapular rash, jaundice, hepatosplenomegaly, diarrhea
Usually bone marrow and liver transplant
Irradiated, immunocompromised host
Grafted T cells reject cells with "foreign" proteins in host → resulting in severe organ dysfunction


DrugMechanismClinical UseToxicity
CyclosporineBinds to cyclophilins--> complex blocks calcineurin → inhibits NFAT (trxn factor) production--> prevents IL-2 trxn/ production= NO T-CELL ACTIVATIONTransplant Rejection Prophylaxis
Autoimmune→ RA, Psoriasis
Nephrotoxic, HTN, hyperlipidemia, hyperglycemia, neurotoxicity, gingival hyperplasia, hirsutism
Tacrolimus (FK-506)Similar to cyclosporin but binds to FK-binding protein to inhibit calcineurin/IL-2Transplant rejection prophylaxisSimilar to cyclosporine but no gingival hyperplasia and hirsutism
Sirolimus (rapamycin)inhibits mTOR (tranducing signal in response to IL-2)
inhibits response to IL-2
Inhibits trxn of proliferation gene--> NO T-cell activation or B cell differentiation
Immunosuppression after KIDNEY transplantation in combination with cyclosporin= synergistic
also used w drug-eluting stents
Hyperlipidemia, thrombocytopenia, leukopenia, anemia (pancytopenia/ BM suppression)
*NO nephrotoxicity (unlike calcineurin inhibitors)
AzathioprineAntimetabolite precursor of 6MP → interferes with the metabolism and synthesis of nucleic acids
Toxic to proliferating lymphocytes
Transplant rejection prophylaxis
autoimmune disorders (RA, Crohns, glomerulonephritis, ect)
Bone marrow suppresion&rarr: pancytopenia
Active metabolite (mercaptopurine) is degraded by xanthine oxidase → ↑ TOXIC w/ allopurinol
Monoclonal Ab blocks/binds IL-2 Receptor
NO T -cell activation and NO B-cell proliferation
Kidney transplant, rejection prophylaxisEdema, HYN, tremor

Recombinant cytokines

AgentClinical uses
Aldesleukin (interleukin-2)Renal cell carcinoma
metastatic melanoma
Epoetin alfa (erythropoietin)Anemias (esp in renal failure)
Filgrastim (granulocyte colony-stimulating factor)Recovery of bone marrow
Sargramostim (granulocyte-macrophage colony-stimulating factor)Recovery of bone marrow
a-interferonHep B & C
Kaposi's sarcoma
Malignant melanoma
gamma-interferonChronic granulomatous disease
Oprelvekin (interleukin-11)Thrombocytopenia
Romiplostim, eltrombopagThrombocytopenia

Therapeutic antibodies

AgentTargetClinical Use
MuromonabCD3Prevent acute transplant rejection
Digoxin Immune FabDigoxinAntidote for digoxin intox
InfliximabTNF-aCrohn's disease
Psoriatic arthritis
Ankylosing spondylitis
AdalimumabTNF-aCrohn's disease
Psoriatic arthritis
AbciximabGlycoprotein IIb/IIIaPrevent cardiac ischemia in unstable angina and with percutaneous coronary intervention
Trastuzumab (Herceptin)HER2HER2-overexpressing breast cancer
RituximabCD20B cell non-Hodgkin's lymphoma
OmalizumabIgEAdditional line of tx for severe asthma