The Complement System

The complement system consists of several plasma proteins that work together to opsonize microbes, to promote the recruitment of phagocytes to the site of infection, and in some cases to directly kill the microbes (Fig. 4-9). Complement activation involves proteolytic cascades, in which an inactive precursor enzyme, called a zymogen, is altered to become an active protease that cleaves and thereby induces the proteolytic activity of the next complement protein in the cascade. As the cascade proceeds, the enzymatic activities result in tremendous amplification of the amount of proteolytic products that are generated. These products perform the effector functions of the complement system. Other proteolytic cascades include the blood coagulation pathways and the kinin-kallikrein system that regulates vascular permeability.

The first step in activation of the complement system is recognition of molecules on microbial surfaces but not host cells, and this occurs in three ways, each referred to as a distinct pathway of complement activation.

• The classical pathway, so called because it was discovered first, uses a plasma protein called C1q to detect antibodies bound to the surface of a microbe or other structure (Fig. 4-10). Once C1q binds to the Fc portion

Initiation of complement activation

Classical pathway Antibody

Early steps

C3b is deposited on microbe

C3b is deposited on microbe

Classical pathway Antibody

Mannose ¿

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