| 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.
Outline
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 splits C2
and C4 into C2b and C4b, whichs bind together to form C3-convertase. The C1 complex is inhibited by C1-inhibitor.
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.
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).
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