Complement system

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The \complement system is a complex biochemical cascade of the immune system, leading to cytolysis, chemotaxis, opsonization and inflammation, it can mark pathogens for phagocytosis. It consists of more than 35 proteins. 12 which are directly involved in the complement pathways, while the rest have regulatory functions. There are three biochemical pathways which activates the complement system.

classical pathway
alternative pathway
mannan-binding lectin pathway

The three pathways all generate homologous variants of the protease, C3-convertase. C3-convertase initiates the membrane attack pathway which results in the membrane attack complex (MAC), consisting of C5b, C6, C7, C8, and polymeric C9. MAC is the cytolytic endprodut of the complement cascade, it forms a transmembrane channel which causes osmotic lysis of the target cell.

Classical pathway is triggered by activation of the C1-complex, either by C1q binding to antibodies complexed with antigens, or by binding C1q to the surface of the pathogen. The C1-complex splits C2 and C4 into C2b and C4b, whichs bind together to form C3-convertase. Alternative pathway is triggered by C3 hydrolysis directly on the surface of a pathogen. It does not rely on a pathogen-binding protein like the other pathways. In the alternative pathway C3 is split into C3a and C3b. Some of the C3b is bound to the pathogen where it will bind to factor B, this complex will then be cleaved by factor D into Ba and the alternative pathway C3-convertase, Bb. Lectin pathway is homologous to the classical pathway, but with the opsonin, mannan-binding lectin(MBL), instead of C1q. This pathway is activated by binding mannan-binding lectin to mannose residues on the pathogen surface, which activates the MBL-associated serine proteases, MASP-1 and MASP-2, which can then split C4 and C2 into C4b and C2b which then binds together to form C3-convertase, like in the classical pathway.

It is thought that the complement system might play a role in alzheimer's,asthma, lupus erythematosus, arthritis, autoimmune heart disease and multiple sclerosis.