Complement System
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Introduction
The complement system is composed of 20 proteins and their split products. It is an important part of both the innate and adaptive immune response
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Activation
The critical step of complement activation is cleavage and activation of C3. This can happen in one of three ways.
The classical pathway is triggered by the binding of the Fc region of antibodies such as IgG or IgM, bound to antigen, to complement C1. This is called 'fixing' complement. Pentameric IgM is particularly good at fixing complement.
The alternative pathway is triggered by microbial surface products (ie endotoxin or LPS) or various other molecules
The lectin pathwayis triggered by mannose-binding lectin directly activating C1.
Each of these pathways activates C3 convertase, splitting C3 in C3a and C3b.
C3b binds with other complement proteins to form C5 convertase, liberating C5a and C5b. C5b then goes on to activate C6-C9.
Function
- C3a and C5a (anaphylatoxins) stimulate histamine release from mast cells, inducing vasodilation
- C3a and C5a are chemotactic for neutrophils, monocytes, eosinophils, and basophils.
- C5a induces lipoxygenase breakdown of arachidonic acid, producing leukotrienes and causing smooth muscle contration and chemotaxis
- C3b binds to bacterial cell walls, acting as an opsonin to induce phagocytosis by macrophages and neutophils.
- C3b continues complement cascade; activated C9 forms MAC attack, leading to microbe lysis.
Measuring C3 and C4 predict involvement and severity of autoimmune diseases as immune complex formation leads to complement fixation.
Decreased levels of complement can occur in nephritic syndrome, membranoproliferative glomerulonephritis, SLE, cryoglobulinemia, vasculitis, serum sickness, liver disease, or malnutrition.
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