Complement system

From Academic Kids

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: the classical complement pathway, the alternate complement pathway and the 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 endproduct of the complement cascade, it forms a transmembrane channel which causes osmotic lysis of the target cell.

Classical pathway

The 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 is inhibited by C1-inhibitor. The C1-complex now binds to and splits C2 and C4 into C2a and C4b. C4b and C2a bind to form C3-convertase (C4b2a complex). Production of C3-convertase signals the end of the Classical Pathway, but cleavage of C3 by this enzyme brings us to the start of the Alternative Pathway.

Alternative pathway

The 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. In other words, after hydrolysis of C3, C3b complexes to become C4b2a3b, which cleaves C5 into C5a and C5b. C5a and C3a are known to trigger [mast cell]degranulation. C5b with C6, C7, C8, and C9 (C5b6789) complex to form the membrane attack complex, also known as MAC, which is inserted into the cell membrane ("punches a hole") to initiate cell lysis.

Lectin pathway

The 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.

Role in disease

It is thought that the complement system might play a role in many diseases with an immune component, such as Alzheimer's disease, asthma, lupus erythematosus, various forms of arthritis, autoimmune heart disease and multiple sclerosis.

Deficiencies of the terminal pathway predispose to both autoimmune disease and infections (particularly meningitis).de:Komplementsystem fr:Système du complément


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