Alternative pathway of complement system activation

Immunology

Complement system

Alternative pathway of complement system activation

Activation of the complement system occurs on the cell surfaces as on bacterial cell. The activation of complements is activated by antibodies, they bind with the bacterial cell surfaces antigens. The C1 complement complex made up of one molecule of C1q two molecules of C1r and two molecules of C1s binds to the aggregated antibody molecules on the surface of the bacteria. Binding of the C1 complex with the antibodies results in the activation by cross-protealisis of the C1r and the C1s proteases. Active C1s cleaves and activates the complement protein C4 releasing a small peptide fragment C4a which acts as an a**toxin. The remaining large fragment C4b which contains a labile thioester bond covalently attaches with the surface of the bacterium through the formation of ester and amide linkages. The C2 pro-enzyme binds with the C4b and is then cleaved by the activated C1s releasing a small peptide c2b this leads to a small protease C4bC2a also known in the classical complement pathway C3 convertase. The C4bC2a enzyme binds C3, cleaving and releasing an another aphlotoxin material C3a. While the other C3b portion which also contains a labile thioester bond attaches with the C4bC2a complex forming the C4bC2aC3b protease i.e., C3/C5 convertase. Many molecules of C3  can be cleaved by C3/C5 convertase releasing many molecules of C3a. The remaining C3b complex are able to covalently attaches with the bacterial cell surface decorating with many molecules of C3b, that can induce phagocytosis of the bacteria. The C3/C5 convertase also cleaves and activates C5 and again a small peptide of C5a is released. This is opponent to naphlotoxin and is also most important chemoattractant derived from the complement system. The large fragment C5b acts to initiate the formation of the membrane attack complex (MAC) the terminal stages of the complement cascade. In this process the C5b assembles with the C6 and C7. The C5b itself is not membrane associated, the C7 complex allows the molecule to insert itself into the bacterial cell membrane. The C8 complex also binds with the C5bC6C7 complex and insert itself into the bacterial cell membrane. The C5bC6C7C8 complex catalyses the assembly of many molecules of C9 to create a cylindrical pore spaning the cell membrane. The pore disrupts the ionic and osmotic balance across the cell membrane and thus kills the bacterial cell.

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Complement system activation