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Hypersensitivity Reactions, Hypersensitivity Type I Allergic Rxn -results from Ag to IgE, bound to FcεRI receptor on Mast cell/baso/eos ->cross-linking of receptor ->chemical release block IgE receptor for Tx, Allergic Rxn -results from Ag to IgE, bound to FcεRI receptor on Mast cell/baso/eos ->cross-linking of receptor ->chemical release block IgE receptor for Tx Allergy Triggers Mostly enzymes, some enz. inhibitors Der p 1-from dust mites->cleaves occludin ->gains access thru airway epith ->DCs take up, present for Th2 priming, Immune complex-mediated Dz -Ag:AB (IgG) aggregates -deposit in blood vessels ->Fc binds WBCs->activation ->Arthus rxn-localized -larger aggregates fix complement ->monocytic clearing of complex Fc Binds Fc receptors on Mast cells, other WBCs ->local inflamm, inc. vasc. perm -PMNs,platelets to site->vessel occlusion, inc. phagocytosis ->"Arthus Rxn" -complement activated->C5a->more WBCs, Allergic Rxn -results from Ag to IgE, bound to FcεRI receptor on Mast cell/baso/eos ->cross-linking of receptor ->chemical release block IgE receptor for Tx Allergy Triggers "Allergens" selectively evoke Th2 cells ->Th2 cells cause isotype switching to IgE, Hypersensitivity Type IV- no ABs involved Gluten Sensitivity (Celiac Dz), Immune complex-mediated Dz -Ag:AB (IgG) aggregates -deposit in blood vessels ->Fc binds WBCs->activation ->Arthus rxn-localized -larger aggregates fix complement ->monocytic clearing of complex Serum Sickness Heterologous serum injected ->induce anti-IgG AB ->clears foreign Ag -widespread, not local -activates mast cells->histamine ->vasculitis, nephritis, arthritis,hives Results after anti-lympho serum (immunosuppressive in xplant pts) and after streptokinase (MI pts), Allergic Rxn -results from Ag to IgE, bound to FcεRI receptor on Mast cell/baso/eos ->cross-linking of receptor ->chemical release block IgE receptor for Tx Phases Immediate phase:Preformed or rapidly synth'ed mediators released-Histamine, PGs ->inc. vasc perm, contract sm. mm., IgG or IgM-mediated destruction of blood cells -ABs bind to antigen adsorbed to blood cells -like PCN-adsorbs to cells ->anti-drug AB binds, opsonizing cell Nucleated Cells More resistant b/c complement reg. proteins -MAC endo-, exocytosed, Ag binds IgE, cross-links ->secretes IL-4,13 express CD40L ->B cells make more IgE ->self-sustaining allergic rxn (goal of Tx) (can occur at inflam site) Degranulation Mast Cell-"great orchestrator" - Release: Histamine-inc. local blood flow, perm. Chymase, tryptase, serine esterases ->activate metalloproteinases ->matrix/tissue destruction TNF-a->activate endoth->adhesion molecs ->inflamm WBCs, lymphos Make and release: Chemokines, leukotrienes, cytokines(IL-4,13) More TNF-a Tx-anti-histamines-block H1, H2 lipoxygenase inhibitors Cromolyn sodium-block Ca++ influx into mast Theophyline-inhibit degran of mast Cortisone-reduce histamine levels, Hypersensitivity Type III Immune complex-mediated Dz -Ag:AB (IgG) aggregates -deposit in blood vessels ->Fc binds WBCs->activation ->Arthus rxn-localized -larger aggregates fix complement ->monocytic clearing of complex