More Immuno

eesohbel's version from 2015-07-13 21:16

Hypersensitivity Types i

Question Answer
What are the 4 types of Hypersensitivity?Type 1: Anaphylactic and atopic
Type 2: Cytotoxic
Type 3: Immune complex
Type 4: Delayed (T-cell-mediated) type
Free antigen cross-links IgE onto Mast cellsType 1
What is the mechanism of Type 1?IgE cross links on mast cells, triggering release of vasoactive amines
Vasodilation and increased vascular permeability results in anaphylaxis
Antibody binds to fixed antigen on target cellType 2
What is the mechanism of Type 2?1. Opsonization and phagocytosis
2. Complement and Fc mediated inflammation
3. Antibody mediated cell dysfunction
IgG immune-complex mediatedType 3
What is the mechanism of Type 3?Antigen-antibody complex against soluble antigens activate complement
Neutrophils release lysosomal enzymes
T-cell mediatedType 4
What is the mechanism of Type 4 hypersensitivity?Sensitized T cells release cytokines that lead directly to macrophage activation
Which type does not involve antibodies?Type 4
Examples of Type 4T's
Transplant rejections
TB skin tests
Touching (contact dermatitis)
What is the mechanism of Serum sicknessImmune complex mediated (type 3)
Antibodies to foreign proteins, ex. drugs as haptens
Immune complexes form & deposit in membranes
(takes 5 days)
Arthus reactionType 3: Local subacute antibody-mediated hypersensitivity
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 2Coomb's test (direct or indirect)
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 (hives), arthralgias, proteinuria, lymphadenopathy
5-10 days after antigen exposure
Test for Type 3Immunofluorescent staining
Test for Type 4Patch test, PPD
Immediate, anaphylactic, atopic (may occur in part of the body that's not in contact with the allergen)Type 1
Disease tends to be specific to tissue or site where antigen is foundType 2
Can be associated with vasculitis and systemic manifestationsType 3
Response is delayed and does not involve antibodiesType 4
What is a direct Coomb's test?Antibody to the autoantibody.
What is the mechanism of anaphylaxis?1. Free antigen cross-links IgE
2. Mast cell and basophil degranulation
Release of ~histamine and tryptase
What enzyme is a marker of mast cell activation?Tryptase (confirm dx of anaphylaxis)


Question Answer
What are the three ways to activate complement?Classic, Alternate and Lectin
How is Classic pathway activated?IgG or IgM bind to C1
How is the Alternate pathway activated?Microbe surface molecules (can be spontaneosu)
How is the Lectin pathway activated?Mannose or other sugars on surface of microbe
C3a, C5aanaphylaxis
C5aneutrophil chemotaxis
C5b-9 fncytolysis by MAC
MAC defends what?gram-negative bacteria
OpsoninsC3b and IgG - 1°
C3b also helps clear immune complexes
InhibitorsDecay-accelerating factor
C1 esterase inhibitor
prevents complement activation on self cells (RBCs)
C1 esterase inhibitor deficiency→ hereditary angioedema
ACE inhibitors are contraindicated
C3 deficiency→ severe, recurrent pyogenic sinus and respiratory tract infections
↑ susceptibility to type III hypersensitivity reactions
C5-C9 deficiencies→ recurrent Neisseria bacteremia
DAF (GPI anchored enzyme) deficiency→ complement-mediated lysis of RBC's and paroxysmal nocturnal hemoglobinuria (PNH)
What are the 2 most important opsonins?C3b and IgG

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 2
Graft-versus-host diseaseType 4
PPDType 4
Contact dermatitisType 4
Allergic reaction to blood transfusionType 2
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-HistoneDrug-induced lupus
Rheumatoid factorRheumatoid arthritis
Anti-CCP [Cyclic Citrullinated Peptide]Rheumatoid arthritis
Anti-CentromereScleroderma (CREST syndrome)
Anti-DNA topoisomerase IScleroderma (diffuse)
- aka Anti-Scl-70
Anti-MitochondrialPrimary Biliary Cirrhosis (PBC)
IgA Anti-EndomysialCeliac disease
IgA Anti-Tissue TransglutaminaseCeliac disease
Anti-Basement membraneGoodpasture's syndrome
Anti-DesmogleinPemphigus Vulgaris
Anti-MicrosomalHashimoto's thyroiditis
Anti-ThyroglobulinHashimoto's thyroiditis
Anti-Jo-1Polymyositis, dermatomyositis
Anti-SRPPolymyositis, dermatomyositis
Anti-Mi-2Polymyositis, dermatomyositis
Anti-RoSjogren's syndrome
- aka Anti-SSA
Anti-LaSjogren's syndrome
- aka Anti-SSB
Anti-U1 RNP (Ribonucleoprotein)Mixed CT
Anti-Smooth muscleAutoimmune hepatitis
Anti-Glutamate decarboxylaseType 1 DM
c-ANCA (PR3-ANCA)Granulomatosis with polyangiitis (Wegener's)
p-ANCA (MPO-ANCA)Microscopic polyangiitis
Churg-Strauss syndrome
Anti-IgGRheumatoid arthritis
Mixed CT
Anti-CardiolipinSLE: Antiphospholipid syndrome.
- False VDRL and False increase PTT
Anti-Beta-2 GlycoproteinAntiphospholipid syndrome: Hypercoagulable state
+/- SLE
IgM-anti-Fc of IgGRheumatoid factor


Question Answer
GiardiaX-linked Agammaglobinemia
Common Variable ImmunoDeficiency (CVID)
-No B-cells
EnterovirusX-linked Agammaglobinemia
Common Variable ImmunoDeficiency (CVID)
-No-B cells
Mucosal infection, viralSelective IgA deficiency
Anaphylaxis to blood transfusionSelective IgA deficiency
AtopySelective IgA deficiency
Recurrent fungal infectionDiGeorge Syndrome
-No T-cells
Recurrent viral infectionDiGeorge Syndrome
-No T-cells
Chronic DiarrheaSCID
Candida (thrush)SCID
Disseminated mycobacterial infectionIL-12 Deficiency
- Can't differentiate T cells
EczemaHyper-IgE (Job syndrome)
Wiskott Aldrich Syndrome (eczema on trunk)
ThrombocytopeniaWiskott-Aldrich Syndrome
Recurrent pyogenic infectionWiskott Aldrich Syndrome
Hyper IgM syndrome
Pneumocystis PneumoniaHyper-IgM syndrome
- Can't class switch
CMVHyper-IgM syndrome
- Can't class switch
CryptosporidiumHyper-IgM syndrome
- Can't class switch
Recurrent Sinusitis and pneumoniaSelective IgA deficiency
AsymptomaticSelective IgA deficiency

Immune deficiencies

Question Answer
Recurrent bacterial infections (after 6 months) in BoysBruton's X-linked agammaglobulinemia
Mechanism of Bruton's agammaglobulinemiaNo B-cell maturation d/t defect in BTK, a tyrosine kinase gene
↓ # of B cells
↓ immunoglobulins of all classes
Higher incidence of infections (URI, GI) but mostly asymptomaticSelective IgA deficiency
IgA<7 mg/dL
False-positive B-HCG testSelective IgA Deficiency
Anaphylaxis to blood transfusion?Selective IgA Deficiency
Mechanism of Selective IgA Deficiency?Autoimmune disease
20-30 y.o. with recurrent URI and lymphomaCommon variable immunodeficiency (CVID)
Mechanism of Common variable immunodeficiency (CVID)Defect in B-cell maturation, but normal # of B cells
↓ plasma cells
↓ immunoglobulins
Recurrent viral/fungal infections + Tetany (hypocalcemia) + Congenital heart problemosDiGeorge syndrome
↓ T cells, ↓ PTH, ↓ CaDiGeorge syndrome
Mutation in DiGeorge syndrome22q11 deletion
Mechanism of DiGeorge syndromeFailure of the 3rd and 4th pouches (endoderm) development
Thymic aplasia
Disseminated mycobacterial (TB) infectionsIL-12 receptor deficiency
Mechanism of IL-12 deficiency↓ Th1 response
↓ IFN-gamma
Cold (noninflamed) staphylococcal abscesse+Coarse facies+Eczema+Retained primary TeethHyperIgE (Job's syndrome)
Mechanism of Job's syndromeTh1 can't make IFN-gamma → neutrophils can't respond to chemotactic stimuli
↑ IgEJob's syndrome (Hyper IgE)
Candida albicans infections of skin and mucous membranesChronic mucocutaneous candidiasis
T cell dysfn
↑ IgE
Failure to thrive + Chronic diarrhea + Mucocutaneous candidaSCID
Mechanism of SCIDAdenosine deaminase deficiency
Defect in T-cell IL-2 receptors (X-linked)
No thymusSCID (no T-cells) or DiGEorge
No germinal center in LNSCID (no T-cells)
T-cell recombinant excision circlesSCID
Treatment for SCIDbone marrow transplant
Cerebellar defects
Spider angiomas
IgA deficiency
Mechanism of Ataxia telangiectasiaDefects in the ATM gene which codes for DNA repair enzymes
↑ AFPAtaxia telangiectasia
Severe pyogenic infections early in lifeHyper-IgM syndrome
Mechanism of Hyper-IgM syndromeDefective CD40L on helper T cells → inability to class switch
↑ IgM
↓↓ IgG, IgA, IgE
Hyper-IgM syndrome
Recurrent infections+Eczema+Thrombocytopenic purpuraWiskott-Aldrich syndrome
Mechanism of Wiskott-Aldrich syndromeX-linked mutations: T cells unable to recognize actin cytoskeleton
↑ IgE, IgA
↓ IgM
Wiskott Aldrich syndrome
Recurrent bacterial infxns without pus formation+Delayed umbilical cord separationLeukocyte adhesion deficiency (type 1)
Mechanism of Leukocyte adhesion deficiencyDefect in LFA-1 integrin (CD18) protein on phagocytes &rarr
- Neutrophils unable to respond to chemotactic stimuli
Recurrent pyogenic Staph and Strep infections+Peripheral neuropathy+Partial albinismChediak-Higashi syndrome
Mechanism of Chediak-Higashi syndromeAR - microtubule dysfunction in phagosome-lysosome fusion
Giant granules in neutrophilsChediak-Higashi syndrome
↑ susceptibility to catalase-positive organisms (Staph aureus, E.coli, Aspergillus)Chronic granulomatous disease
Mechanism of Chronic Granulomatous diseaseNo NADPH oxidase
Abnormal dihydroRhodamine flow cytometry Chronic Granulomatous disease
Recurrent respiratory infections+DextrocardiaKartagener's
Defect in KartagenerPrimary ciliary diskinesia due to failure of Dynein arms to form correctly
Recurrent respiratory infection + InfertilityCystic fibrosis (Kartagener if dextrocardia is present)
Mechanism of cystic fibrosisDefective CFTR channels
Mechanism of Hyper-IgMImpaired immunoglobulin gene re-arrangement
Severe bacterial and fungal infections+granuloma formationChronic granulomatous disease


Question Answer
Syngeneic graftFrom identical twin or clone
AllograftFrom another person
Xenograftfrom different species
HyperacutePre-existing antibodies against donor
Type-II HSHyperacute
Widespread thrombosisHyperacute
CD8+ against donor MHCAcute
Vasculitis w/lymphocytic infiltrateAcute
Reversible w/immunosuppressionAcute
CD4+ against donor peptides on APC'sChronic
Months to yearsChronic
Type-IV HSGraft-vs-Host
Maculopapular rash+Jaundice+HepatosplenomegalyGraft-vs-Host


Question Answer
Which vaccines are live attenuated?Polio (sabin)
Yellow fever
BCG (tuberculosis)
Influenza (Intranasal)
[Attention! Please Vaccinate Young Baby Infants with MMR Regularly!]
What immune response is elicited by live attenuated vaccines? Cellular and Humoral
Lifelong immunity
What is a live attenuated vaccine?Virus that has lost its pathogenicity but still grows in human cells.
- Elicits a mini infection.
Polio (Sabin)Live attenuated
VaricellaLive attenuated
Yellow feverLive attenuated
Influenza (intranasal)Live attenuated
MMRLive attenuated
RubellaLive attenuated
Which vaccines are inactivated/killed?Rabies, Influenza, Polio (salk), Hepatitis A
What immune response is elicited by inactivated/killed vaccines?Humoral only
What is an inactivated/killed vaccine?Pathogen is inactivated and the epitope is given on surface antigen
Influenza (injection)inactivated/killed
Hepatitis Ainactivated/killed
Polio (salk)inactivated/killed
Which vaccines are egg based?Influenza and Yellow fever
safer but booster shots are usually required
What is passive immunity?Receiving preformed antibodies
Ex. Breast milk IgA, Maternal IgG, Monoclonal antibodies
Which S. pneumo vaccine is given to the elderly and the young?PCV13: S. pneumo conjugate vaccine of capsular polysaccharides.
Covalently attached to recomhbinant, inactivated diptheria toxin
What kind of immune response is elicited by the PCV13 vaccine?T cell dependent. Better immunogenicity
- Induces IgG response with higher affinity antibodies and Memory cells.

Arachidonic acid

Question Answer
Membrane lipids --> arachidonic acid (phosphatidyl inostitol)Phospholipase A2
Inhibits phospholipase A2Steroids
Arachidonic acid --> hydroperoxidesLipoxygenase
Inhibits lipoxygenaseZileuton and Colchicine
Leukotriene receptor antagonist-Lukasts
Inhibits cyclo-oxygenaseNSAIDs, Acetominophen, Aspirin
Arachidonic acid --> endoperoxidesCyclooxygenase (COX1, COX2)
Neutrophil chemotaxisLTB4
Decreases platelet aggregationPGI2
Decreases uterine tonePGI2
Decreases vascular tonePGE2
Increases painPGE2
Increases uterine tonePGE2
Increases temperaturePGE2 gives you fEver
Increases platelet aggregationTXA2
Increases vascular toneTXA2