Overview Auto immune disease or excess response to foreign stimulus categorized by type of effector mechanism Types I, II, and III are all antibody mediated Type IV is TH1 mediated Commonalities between all types requires a sensitizing exposure reactions occur in later exposures Timeline [Fastest] Type I < Type II / III < Type IV [Slowest] Type I Immune relationship IgE mediated only type fast within minutes of re-exposure protective against parasites atopic or alleric responses effector cells basophil, mast cell Mechanism of tissue injury sensitizing exposure followed by a reaction exposure Presentation vasodilation of post capillary venules inflammation bronchoconstriction intestinal hypermotility tissue damage Disorder anaphylaxis bronchial/trachial constriction systemic vasodilation death e.g. bee sting, some food/drug allergies treat with EpiPen (epinephrine) allergic rhinitis "hay fever" asthma bronchial/trachial constriction inflammation mucus Test scratch test wheal and flare in vivo skin edema, reddening near scratch introduction radioimmunosorbent assay Type II Immune relationship Antibody mediated IgM, IgG bind to antigen complement activation results in lysis via membrane attack complex or phagocytosis effector cells cytotoxic PMN, macrophages, NK cells non-cytotoxic none Mechanism of tissue injury antibodies lead to disease via three different processes activation of complement or opsonization recruitment of neutrophils and macrophages that incite tissue damage interfere with normal receptor function Presentation disease localized to specific tissues where antibodies are present Disorder cytotoxic autoimmune hemolytic anemia (HDNB) anti-RBC antibodies (other than ABO proetins) destruction of RBC hemolysis, anemia idiopathic thrombocytopenic purpura anti-platelet antibodies destruction of platelet thrombocytopenia, bleeding erythroblastosis fetalis aka Hemolytic disease of the newborn (HDNB) RhD- mother must have had previous RhD+ pregnancy where she was exposed to fetal blood delivery, termination anti-RhD+ IgG that can cross the placenta attack fetus prophylaxis/treatment RhoGAMTM anti-RhD IgG given to Rh- mother at 28 weeks gestation within 72 hours of delivery prevents mother from developing B-cell memory of RhD acute hemolytic transfusion reactions anti-ABO RBC protiens IgM (isohemagglutinins) hemolysis acute rheumatic fever antibody against streptococcal cell wall binds healthy tissue heart and joint inflammation Goodpasture's syndrome anti-type IV collagen antibody lung alveoli lung hemmorhage kidney glomeruli nephritis linear deposits unlike post-streptococcal glomerulonephritis lumpy bumpy pattern bullous pemphigoid anti-hemidesmosomes at the dermoepidermal junction separation of epidermis from basement membrane results in formation of tense blisters pemphigus vulgaris autoantibodies against desmoglein 1 and/or 3 in the epidermis results in acantholysis and formation of flaccid blisters non-cytotoxic Graves' disease anti-TSH receptor antibody stimulates T3/4 release hyperthyroid followed by hypothyroid myasthenia gravis anti-Acetylcholine receptor antibody inhibits muscle stimulation muscle weakness, paralysis pernicious anemia anti-intrinsic factor antibody inhibits binding of IF to receptor decreased vit B12 absorbtion >> macrocytic anemia type II diatbetes anti-Inuslin receptor antibody inhibits binding of insulin hyperglycemia Test direct Coombs test measures IgG/C3b bound to RBCs "direct attachment" indirect Coombs test measures free antibodies in serum Type III Immune relationship Immune complex mediated antigen-antibody (IgG) complexes form antigens can be self or foreign effector cells PMN, macrophages Mechanism of tissue injury complexes are filtered out of circulation and deposited in healthy tissue neutrophils attracted and complement activated by Ab-Ag complex neutrophils release lysosomal enzymes healthy tissue damaged Presentation widespread mobility of Ab-Ag complexes allows for vasculitis and systemic manifestations compared to type II with generally localized reactions Disease SLE anti-dsDNA, anti-Sm, anti-Rho antibodies in complex with antigen butterfly facial rash, nephritis, arthritis, vasculitis Serum sickness antibodies to the foreign proteins are produced and complex formed takes 5 days e.g., horse antithymocyte globulin antibody in transfused serum now more common from drugs e.g., beta-lactams, sulfa drugs, anti-venin fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure usually self-limited, and will resolve with withdrawal of the offending agent management may also involve symptomatic treatment e.g., antihistamines or steroids Arthus reaction antigen-antibody complexes cause the Arthus reaction a local subacute antibody-mediated hypersensitivity (type III) reaction intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin characterized by edema, necrosis, and activation of complement rheumatoid arthritis anti-IgM Fc region antibody complex with antigen joint pain, decrease in range of motion polyarteritis nodosa deposition of complexes in medium sized arteries poststreptococcal glomerulonephritis anti-Streptococcal cell wall antibody with antigen nephritis "lumpy bumpy pattern" on immunofluorescence staining large complexes so they cannot coat the entire membrane like in Goodpasture's (small IgG) hypersensitivity pneumonitis inhaled dust forms an Ab-Ag complex e.g. farmer's lung Test immunofluorescent staining Type IV Immune relationship senstitizing antigen exposure memory T-lymphocytes generated effector cells CTL, Th1 , macrophages Mechanism of injury sensitized T lymphocytes encounter antigen and then release lymphokines mainly IFN-γ leads to macrophage activation TNF secretion no antibody involved cell-mediated toxicity, therefore not transferable by serum Presentation response is delayed and does NOT involve antibodies (vs. types I, II, and III) or complement Disease type 1 DM T-cells against islet cells, insulin, glutamic acid decarboxylase multiple sclerosis T-cells against myelin of CNS Guillain-Barré syndrome T-cells against myelin of PNS Hashimoto's thyroiditis T-cells against antigen in thyroid graft-versus-host disease T-cells of transplant origin become activated against MHC of host PPD (test for M. tuberculosis) T-cells of skin against tuberculin/mycolic acid contact dermatitis e.g. poison ivy, nickel allergy pruritus, rash, skin lesions Test patch test e.g. PPD, patch containing any antigen placed on skin References