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Bee Sting, Bee sting releases venom locally Venom binds Venom binds IgE (on mast cells) ->secretes IL-4,13 express CD40L ->B cells make more IgE ->self-sustaining allergic rxn, Mast Cell-"great orchestrator" Release: Histamine-inc. local blood flow, perm. Chymase, tryptase, serine esterases ->activate metalloproteinases ->matrix/tissue destruction TNF-a->activate endothelium->adhesion molecs ->inflammatory WBCs, lymphocytes Make and release: Chemokines, leukotrienes, cytokines(IL-4,13) More TNF-a Tx-anti-histamines-block H1, H2 Activates Eosinophils In MALT, respiratory tree, GALT 2 effector fcns: 1.release free radicals, toxic proteins Major Basic Protein->mast, baso degranulate ->can cause heart, nerve damage 2.PGs, LTs, cytokines->amplify inflammation Activated Th2 release IL-5->increase eos in blood -eotaxins 1-3 needed for migration to tissue and activation -CCR3-eos chemokine receptor Activation->express FceRI->bind IgE, Ag Tx-inhibit IL-5, block CCR3, Mast Cell-"great orchestrator" Release: Histamine-inc. local blood flow, perm. Chymase, tryptase, serine esterases ->activate metalloproteinases ->matrix/tissue destruction TNF-a->activate endothelium->adhesion molecs ->inflammatory WBCs, lymphocytes Make and release: Chemokines, leukotrienes, cytokines(IL-4,13) More TNF-a Tx-anti-histamines-block H1, H2 Activates Basophils Present at inflammatory loci -express FceRI, bind IgE Ag, cytokine activation-> ->histamine, IL-4,13 released, Mast Cell-"great orchestrator" Release: Histamine-inc. local blood flow, perm. Chymase, tryptase, serine esterases ->activate metalloproteinases ->matrix/tissue destruction TNF-a->activate endothelium->adhesion molecs ->inflammatory WBCs, lymphocytes Make and release: Chemokines, leukotrienes, cytokines(IL-4,13) More TNF-a Tx-anti-histamines-block H1, H2 Mast Cell Site-specific effects Subcutaneous->local inflammation inhaled, transepithelial->sm. mm. contraction ->difficulty expelling air, irritation Ingested, transepith->emesis, diarrhea ->to bloodstream->hives Bloodstream->histamine->anaphylaxis Tx-epinephrine-on b2-adrenergic receptors -constrict vessels->raise bp, dec. perm, relax bronchii, Venom binds IgE (on mast cells) ->secretes IL-4,13 express CD40L ->B cells make more IgE ->self-sustaining allergic rxn Degranulation Mast Cell-"great orchestrator" Release: Histamine-inc. local blood flow, perm. Chymase, tryptase, serine esterases ->activate metalloproteinases ->matrix/tissue destruction TNF-a->activate endothelium->adhesion molecs ->inflammatory WBCs, lymphocytes Make and release: Chemokines, leukotrienes, cytokines(IL-4,13) More TNF-a Tx-anti-histamines-block H1, H2