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The Complement System CHAPTER 13 309 VISUALIZING CONCEPTS Ciqr2S2 ClInh Regulation of the Com plement System (a) Before assembly of convertase activity Cl inhibitor(Cllab)binds CIr2S2, causing dissociation from Clq CAbBP CRl or mcp ion of C4b and C2a is blocked by binding C4b-bindin Factor 1 (C4bBP), complement receptor type l, or membrane protein(MCP) Inhibitor-bound CAb is cleaved by Factor 1 C3 converts CRI, MCP, Factor H pin alternative pathway, CRL, MCP, or Factor H prevent Factor I Q C3f binding of C3b and Factor B C3b DiC hibitor-bound C3b is cleaved by Factor 1 Factor 1 C3 convertase C3c 0 DC3dg (b)After assembly of convertase CAbBP CR Factor H. daf f convertase: C3 convertases are dissociated by C4bBP, CRl, Factor H, and or c3b decay-accelerating Factor (DAF) (c) Regulation at assembly of membrane-attack complex(MAC) protein prevents insertion of C5b67 MAC component into -H Cannot attack nearby cells C5b67 >protein omologous restriction facto (HRF) and membrane inhibite of reactive lysis ( MIRl or CD59)bind C8 1, preventing blocking formation of MAC C5b67 C5b678 Membrane attack complex FIGURE13.9 Regulation of the complement system by regulatory proteins(black)The Complement System CHAPTER 13 309 VISUALIZING CONCEPTS FIGURE 13-9 Regulation of the complement system by regulatory proteins (black). Poly-C9 Association of C4b and C2a is blocked by binding C4b-binding protein (C4bBP), complement receptor type I, or membrane cofactor protein (MCP) 4 In alternative pathway, CR1, MCP, or Factor H prevent binding of C3b and Factor B 1 C1 inhibitor (C1Iab) binds C1r2s2, causing dissociation from C1q C3 convertases are dissociated by C4bBP, CR1, Factor H, and decay-accelerating Factor (DAF) + C3 convertase C2a C4b C4c C4d 2 Inhibitor-bound C4b is cleaved by Factor 1 3 Inhibitor-bound C3b is cleaved by Factor 1 5 C9 C5b678 C8 HRF, MIRL C5b67 C5b678 S protein C5b67 Membrane attack complex C1Inh C1r2s2 Antibody C1qr2s2 (a) Before assembly of convertase activity (b) After assembly of convertase 1 S protein prevents insertion of C5b67 MAC component into the membrane 2 Homologous restriction factor (HRF) and membrane inhibitor of reactive lysis (MIRL or CD59) bind C81, preventing assembly of poly-C9 and blocking formation of MAC (c) Regulation at assembly of membrane-attack complex (MAC) Regulation of the Complement System Factor 1 C4bBP, CRI, or MCP + C3 convertase Factor B C3b C3c Dissociation of convertase; remaining C4b or C3b cleaved by Factor 1 C3f iC3b C3dg Factor 1 C4bBP, CR2 Factor H, DAF Factor 1 CRI, MCP, Factor H Cannot attack nearby cells
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