Biochemistry, Complement

Excerpt

The complement system consists of several complement proteins synthesized by the liver’s Kupffer cells and subsequently found in the body’s blood and tissues. The proteins themselves are both zymogens, meaning they are typically inactive, and are meta-stable when activated, meaning they require a cell surface to remain active. When these complement proteins (mostly named C1 to C9) initiate a cascade that engages both the innate and adaptive immune system, they serve as the first line of defense in response to pathogen attack. One goal of the complement system is the formation of a membrane attack complex (MAC), which compromises the pathogen’s cell wall, causing swelling that ultimately leads to cell death. The complement system is diffusely active within the body, and deficiencies or dysregulation results in immune system deficiencies, autoimmune disorders, or bleeding disorders.

While often considered as part of the innate immune system, this is not entirely the case. One method of complement cascade initiation, the classical activation pathway, involves antibodies and, thus, the adaptive immune system. The other two well-studied pathways are the alternative and lectin activation pathways. Neither requires adaptive immune system activation and, therefore, truly are mechanisms of the innate immune system. Although they differ in mechanisms, the commonly needed step of all pathways is the conversion of C3 to C3a and C3b; the latter is necessary for the formation of the MAC.