Complement System

The complement system consists of about 20 interacting soluble proteins that are made mainly by the liver and circulate in the blood and extracellular fluid. Most are inactive until they are triggered by an infection. They were originally identified by their ability to "complement" the action of antibodies but some components of complement are also pattern recognition receptors that can be activated directly by pathogen associated immunostimulants. 

Complement has a variety of important functions which includes:

(1) opsonization of antigens: including bacteria by phagocytosis. The complement component, C3b is the major opsonin of the complement system. Phagocytic cells, as well as some other cells, express complement receptors that bind C3b, enhancing phagocytosis by these cells. C3b may also act as an adjuvant when coupled with protein antigens. C3b targets the antigen directly to the phagocyte, enhancing the initiation of antigen processing and accelerating specific antibody production.

The coating of soluble immunogen complexes with C3b
is thought to facilitate their binding to complement receptors on erythrocytes which carry these complexes to the liver and spleen. In these organs the complexes are stripped away from the red blood cells and phagocytosed. The terminal sequence of complement activation involves a macromolecular structure called MAC which lyses cells. Gram positive bacteria are generally resistant to complement mediated lysis because the thick peptidoglycan layer in their cell wall prevents insertion of the MAC into the inner membrane.

(2) activation of inflammation: refers to the activation of a complex cascade of nonspecific events due to infection or tissue injury.

(3) clearance of immune complexes: The coating of soluble immunogen complexes with C3b is thought to facilitate their binding to complement receptors on erythrocytes which carry these complexes to the liver and spleen. In these organs the complexes are stripped away from the red blood cells and phagocytosed.

(4) cell lysis: The terminal sequence of complement activation involves a macromolecular structure called MAC which lyses cells. Gram positive bacteria are generally resistant to complement mediated lysis because the thick peptidoglycan layer in their cell wall prevents insertion of the MAC into the inner membrane.

Early components of the complement system and C3 are all proenzymes which are activated sequentially by proteolytic cleavage. The cleavage of each proenzyme in the series activates the next component to generate a serine protease, which cleaves the next proenzyme in the series.

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Viruses have coopted aspects of the complement system to enhance infectivity. EBV and measles, for example, use two membrane proteins of the complement system, CD21 and CD46 as cellular receptors for attachment.

The complement system has been implicated in many autoimmune diseases such a rheumatoid arthritis, systemic lupus erythemaosus, renal diseases, myocarditis, multiple sclerosis, Type I diabetes mellitus and asthma.