Complement System Made Simple ( classical pathway)

The complement system consists of a series of heat-labile serum proteins that are activated in turn. The components normally exist as soluble inactive precursors; once activated, a complement component may then act as an enzyme , which cleaves several molecules of the next component in the sequence. Each precursor is cleaved into two or more fragments. The major fragment has two biologically active sites: one for binding to cell membranes or the triggering complex and the other for enzymatic cleavage of the next complement component . Control of the sequence involves spontaneous decay of any exposed attachment sites and specific inactivation by complement inhibitors. The classical pathway was the first to be described. It is activated by a number of substances, the most widely recognized being antigen–antibody complexes where the antibody is either IgM or IgG (Fig. 1.21). The reaction of IgM or IgG with its antigen causes a conformational change in the Fchregion of the antibody to reveal a binding site for the first component in the classical pathway, C1q. C1q reacts with Fc via its globular heads; attachment by two critically spaced binding sites is needed for activation. The Fc regions of pentameric IgM are so spaced that one IgM molecule can activate C1q; in contrast, IgG is relatively inefficient because the chance of two randomly sited IgG molecules being the critical distance apart to activate C1q is relatively low. IgA, IgD and IgE do not activate the classical pathway. Once C1q is activated, C1r and C1s are sequentially bound to generate enzyme activity (C1 esterase) for C4 and C2 splitting both molecules into “a” and “b” fragments. The complex C b b4 2 is the classical pathway C3 convertase. Other fragments released are C4a, C2a and a vasoactive peptide released from C2. C4b2b cleaves C3 into two fragments, C3a possessing anaphylotoxic and chemotactic activity and C3b that binds to the initiating complex and promotes many of the biological properties of complement. The C4b2b3b complex so generated is an enzyme, C5 convertase which initiates the final lytic pathway Show us your support by SUBSCRIBING,LIKING and SHARING. Connect with us on our website www.medcrine.com Follow us on twitter @medcrine Telegram at https://t.me/medcrine