2-16 - Inhibitory Fc R (Fc RIIB) Fc RIIB ITIM Inhibitory...

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Unformatted text preview: Inhibitory Fc R (Fc RIIB) Fc RIIB ITIM Inhibitory receptor Immunoreceptor tyrosine-based inhibitory motif Fc RI 2 2 Fc RIII 2 Fc RIV Activating receptors ITIM P P ITIM can be phosphorylated by Src family tyr kinases SHIP CH 2 CH 2 CH P P P HO OH O O P Phosphatidylinositol-3,4,5- triphosphate (PIP 3 ) CH 2 CH 2 CH P P HO OH P O O Phosphatidylinositol-3,4- biphosphate OH SHIP phosphatase CH 2 CH 2 CH P P P HO OH O O OH IP 3 DAG PI3K Phosphatidylinositol-4,5- biphosphate PLC Loss of Fc RII increases inammation. Mice Intravenous injection of Ovalbumin Introduce anti-ovalbumin IgG into the lung IgG-Ova immune complex induces inammation (Arthur reaction in the lung) Hemorrhage Neutrophil inltration Increased inammatory cytokine production Enhanced phagocytosis of IgG-opsonized RBC Enhanced inammation in Fc RII decient mice Activating Fc R Inhibitory Fc R C5a Interferon Strong activation by immune complex TGF- IL-10 IL-4 Weak activation by immune complex Regulation of Fc receptor expression Different activities of IgG subtypes IgG2a 2.9x10 7 0.4x10 6 IIB IV Ka IgG2b 1.7x10 7 2.2x10 6 IIB IV IgG1 0.3x10 6 3.3x10 6 IIB III IgG3 IIB A/I=70 A/I=7 A/I=0.1 Fc R-mediated activation +++ +- Antibody therapy Immunization Polyclonal antibody in serum Isolate individual hybridoma clones Monoclonal antibody Ig production Short-lived in culture B cells in spleen recognize different epitopes Myeloma (mouse tumor derived from plasma cells) No Ig production Ig secretion apparatus Immortal Antigen Fusion of B cells with myeloma hybridoma PEG (polyethylene glycol) Ig production Ig secretion apparatus Immortal Hybridoma screening...
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This note was uploaded on 03/25/2010 for the course BIO 360K taught by Professor Bryant during the Spring '09 term at University of Texas at Austin.

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2-16 - Inhibitory Fc R (Fc RIIB) Fc RIIB ITIM Inhibitory...

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