Presentation on theme: "Type II Hypersensitivity: Antibody-mediated cytotoxicity"— Presentation transcript:
1 Type II Hypersensitivity: Antibody-mediated cytotoxicity Results when Ig or IgM bind to cell surface Ag’sActivating ComplementBinding Fc receptors on Tc cells promoting ADCCBoth processes result in lysis of the Ab-coated cellClinical examples of Type II responses include:Certain autoimmune diseases where Ab’s produced vs membrane Ag’sGrave’s Disease – Ab’s produced vs thyroid hormone receptorMyasthenia Gravis – Ab’s produced vs acetylcholine recpetorsAutoimmune hemolytic anemia – Ab’s produced vs RBC membrane Ag’sHemolytic Disease of the NewbornHyperacute graft rejectionBlood Transfusion rxnsGraft rejection
2 Type II Hypersensitivity: Transfusion reactions Produced by mismatched blood typesDestroys foreign RBC by complement-mediated lysis triggered by IgGProduces fever, intravascular clots, lower back pain, Hgb in urineFree Hgb produced has 2 fates:passes to the kidneys – hemoglobinuriaBreaks down to bilirubin..can be toxic
3 Type II Hypersensitivity: Hemolytic Disease of the Newborn Occurs via maternal IgG Ab’s crossing the placentaIn severe cases causes erythroblastosis fetalisMost commonly develops in Rh- mother with Rh+ fetusExposure to Rh+ fetal RBC’s stimualtes prod of memory/plasmaActivation of memory cells in subsequent pregnancy stim IgG Ab’s which can cross the placentamild-severe hemolytic anemia ensues along with bilirubin which affects the brain/CNSTreatment centers on anti-Rh antibodies (Rhogam)Mothers can be tested for anti-Rh antibodies to check for a rise in titreIsolated fetal RBC’s can be checked for anti-Rh IgG w/ Coombs test
5 Type II Hypersensitivity: Drug-induced hemolytic anemia Drugs such as aspirin and antibiotics can bind to the surfaces of RBC’sThese interactions act similar to hapten-carrier conj.Such complexes can trigger Ab-mediated cell lysis by complement activation
6 Type III Hypersensitivity: Immune Complex-mediated cytotoxicity Caused by immune complex deposition in tissuesSmall amts cleared by phagocytic cellsActivates complement which attracts neutrophils and stim Mast cell degranulationDepending on location, rxn can be localized or systemicMost damage stems from activity of NeutrophilsImmune complexes can adhere to tissue making it difficult for Neutrophils to phagocytizeNeutrophils continue releasing lytic enzymes, etc.
7 Type III Hypersensitivity: Localized reactions Arthus rxns:Exposure to an Ag for which there already is a high [c] of AbProduces edema/erythema from damage to bv and tissInsect bitesInhalation of bacteria, fungi, dried fecal matter
8 Type III Hypersensitivity: Systemic (generalized) reactions Produced when large amounts of Ag enter the bloodstreamThe sites of deposition vary; usually in tissues where plasma is filteredEsp. in kidneys, blood vessels, and jointsCan cause tissue damaging rxns:Serum sicknessAutoimmune diseasesDrug reactionsInfectious diseases
9 Type IV Hypersensitivity: Delayed-Type Hypersensitivity Occurs hrs after Ag contact and is mediated by Ag-specific TH1 cells and activated MØTH1 cells secrete:IFN-γ activates MØTNF-α and β upregulate CAM’s on local b.v’sIl-3 and GM-CSF stim bone marrow monocyte outputInitial contact with Ag (sensitization) may induce memory TH1 cells without symptoms
10 Phases of the DTH Response Sensitization – TH1 cells triggered by contact with APCEffector response – produces huge influx of activated MØActivated MØ is more efficient at antigen-presentationRelease of lytic enzymes lead to non-specific destruction of cellsWorks well vs intra-cellular pathogensIf pathogen/particle lingers -> can lead to granuloma formationEx: Mycobacterial pathogens in TB and Leprosy
11 DTH ResponseCytokines released include: TNF-β, GM-CSF, and IFN – γ
12 DTH ResponseType IV rxns marked by time delay and recruitment of MØ instead of Neut’s and Eosino’s
13 Contact Dermatitis Produced by a variety of substances Mostly small molecules attach to a protein in the skinThe Ag-protein complex is processed and presented sensitize TH1 cellsSubsequent exposure activates TH1 cells hrs later MØ infiltrateActivation of MØ causes the inflammation that characterizes the disorder
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