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BIOL 1103 (33)

Immediate hypersensitivity reactions

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BIOL 1103
Tamy Superle

IMMEDIATE HYPERSENSITIVTY REACTIONS Type I Hypersensitivity/ Allergic Reactions Nomenclature: Allergen = antibody that elicits an IgE (REAGIN) response - can be inhaled, ingested, or injected - small proteins or chemicals bound to proteins - very soluble - they display SENSITIZATION (previous exposure elicits a reaction) Allergy = clinical manifestations of reaction ATOPY = genetic predisposition to make IgE’s Immediate Skin Response = WHEAL and FLARE IgER’s (FcER’s) RI – high affinity binding (mast cells, basophils) tetramer (abg2); beta and gamma domains have ITAM motifs trimeric version (no beta) – found in monocytes and DC’s UPREGULATED BY IgE PRESENCE RII – low affinity binding; also called CD23 2 isoforms; neither is homologous to FcERI CONTROL OF IgE SYNTHESIS: 2 SIGNAL HYPOTHESIS 2 SIGNALS work on B – cells 1. IL4/IL13 from Th2 cells, Basophils, and Mast Cells **activates E gene transcription** occurs via JAK/STAT6 pathway 2. CD40/CD40L binding between B and Th2 Cells **activates switch recombination** Secreted IgE’s bind to Mast Cells Crosslinking by allergen causes degranulation, tyrosine kinase activity EARLY PHASE (minutes) skin (wheal, flare, itchiness) airway (sneezing) mediated by histamine/heparin DEGRANULATION leukotriene/prostaglandin synthesis from MEMRANE LIPIDS LATE PHASE (hours) recurrent airway/skin problems mediated by cytokines/chemokines (IL4/IL13) expression and secretion involves other cells’ migration (eosinophils, basophils, lymphocytes) Mediators from mast cells/ basophils (summarized) - granule products (heparin, histamine, tryptase) histamine’s effects: nerve activation (for sneezing/pruritis) vasodilation (tissue swelling/hypotension) gland secretion (musocal) smooth muscle contraction (bronchocontriction, diarrhea) - membrane lipids (leukotriene/prostaglandin) LKT synth. involves PHOSPHOLIPASE A cleavage of membrane
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