The complement system consists of about 31 proteins, acting within a cascade-like reaction sequence, serving as control proteins or as cellular receptors. Some of the proteins are enzymes (C1r, C1s, C2, factor B, factor D), some cofactors, some inhibitors, and other are composed of membrane-integrated proteins.

Complement proteins are made mainly by the liver and circulate in the blood and extracellular fluid. A majority of the protein componetns of the system are syntehsized by liver hepatocytes; however, blood monocytes, tissue macrophages and the epithelial cells lining the gastrointestinal and genitourinary tracts can also synthesize some complement proteins. 

Both in vivo and in vitro studies have confirmed that cytokine mediators of the acute phase response, for example, the interleukins (particularly interlukin y), TNF and dexamethasone can increase the hepatic synthesis of complement proteins 2-5 fold in cultured hepatocytes. (Figueroa, Clinical Microbiology Reviews, July 1991, p. 359-395)

Most complement proteins are inactive until they are triggered by an infection. Most the circulating proteins are innnocuous and as such are regarded as “pro-enzymes”. However, upon initiation there occurs a sequential proteolysis and ensuing activation of these proteins. Activation of a complement protein changes its structure, revealing an “active” site then catalyzes, and usually cleaves, a portion of the next protein in the sequence, ultimately producing a multiple subunit protein complex that lyses the invading cell. 

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 can be activated by any of three pathways, either the antibody-dependent classical pathway, the alternative pathway or the lectin pathway. On activation, these pathways result in the formation of unstable protease complexes, the C3-convertases. The classical pathway C3-convertase, C4b2a, and the AP C3-convertase, C3bBb, are both able to cleave the alpha chain of C3 generating C3b. C3b has the potential to bind covalently to biological surfaces which leads to opsonization for phagocytosis by polymorphonuclear cells and macrophages. When additional C3b is available, the C3-convertases can function as C5-convertases, cleaving C5 and initiating the assembly of the TCC, or the membrane attack complex (MAC), which mediates cellular lysis by insertion of pore-forming protein complexes into targeted cell membranes. (Kaleko, WO2008/106644).