Historically, the term complement was used to refer to a heat-labile serum component that was able to lyse bacteria (activity is destroyed (inactivated) by heating serum at 56 degrees for 30 minutes). However, complement is now known to contribute to host defenses in other ways as well. Complement can opsonize bacteria for enhanced phagocytosis; it can recruit and activate various cells including polymorphonuclear cells (PMNs) and macrophages; it can participate in regulation of antibody responses and it can aid in the clearance of immune complexes and apoptotic cells. Complement can also have detrimental effects for the host; it contributes to inflammation and tissue damage and it can trigger anaphylaxis.
Complement comprises over 20 different serum proteins that are produced by a variety of cells including, hepatocytes, macrophages and gut epithelial cells. Some complement proteins bind to immunoglobulins or to membrane components of cells. Others are proenzymes that, when activated, cleave one or more other complement proteins. Upon cleavage some of the complement proteins yield fragments that activate cells, increase vascular permeability or opsonize bacteria.
Complement system is a highly regulated and multifunctional system that is the major extracellular arm of innate immunity. Its activation results in three major potential outcomes for microbes: cell lysis upon assembly and insertion of the terminal membrane attack complex (MAC), complement mediated opsonization, and the release of anaphylatoxins that enhance local inflammation.
Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of the classical pathway of complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex(MAC) to assist antibodies to kill the bacterium directly (bacteriolysis).
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