Complement Regulator of Complement System: RCA/CCP family

Complement Regulator of Complement System: RCA/CCP family Background

There are two major complement pathways, the classical pathway and the alternative pathway. The classical pathway is activated by immune complexes and results in the covalent attachment of C4b and C3b to foreign surfaces. The alternative pathway is activated by microbes,resulting in attachment of C3b. C4b and C3b serve as the foci for the classical and alternative pathway convertases,respectively,which in turn generate more C3b. Since the attachment of C4b and C3b is relatively non-specific,and can direct damage to normal tissue as well as pathological material, two distinct biochemical mechanisms, decay accelerating activity and factor I-dependent cofactor activity,have evolved to discriminate self from non-self by deactivating C3b and C4b and/or their convertases.

Complement regulatory proteins are plasma and cell membrane molecules that regulate complement activation and protect host cells against complement damage. Certain diseases, such as hereditary angio-oedema, membranoproliferative glomerulonephritis and paroxysmal nocturnal haemoglobinuria, are caused by complement regulator deficiency.

At least six proteins mediate complement activation through interactions with C3b and/or C4b. Memebrane cofactor protein(MCP) and decay accelerating factor (DAF) are widely distributed membrane proteins available to down regulate C3b and C4b on cell surfaces. Factor H and C4 binding protein (C4bp) inhibit fluid phase activation and assist in control on tissues. C3b/C4b receptor or complement receptor 1 (CR1) on leukocytes binds C3b/C4b-bearing immune complexes and on erythrocytes mediates transport of complexes to the liver and spleen for clearance, and complement C3b and C3d receptor or complement receptor 2 (CR2) binds C3d-bearing immune complexes and thereby activates B cells.

Complement Regulator of Complement System: RCA/CCP family References

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