Last reviewed 01/2018

Complement is a series of at least 25 circulating enzyme-precursor proteins whose activation in sequence leads to cell membrane attack. Byproducts of the cascade of sequential proteolysis are mediators influencing vessel tone and chemotaxis during inflammation and innate immune responses. They are interlinked with other plasma protease systems such as the kinin and clotting cascades.

  • complement system represents a large group of independent proteins (denoted by the letter C and followed by a number), secreted by both hepatocytes (liver cells) and monocytes
    • these proteins maybe activated by both the adaptive immune system (classical pathway) or innate immune system (alternative pathway)
    • nomenclature is derived from the fact that the proteins help (“complement”) the antibody response
      • activation of complement via the pathogen itself is known as the alternative pathway
      • in the classical pathway there is the requirement for the interaction of antibody with specific antigen
  • it is possible for mononuclear phagocytes to produce individual components
  • the classical pathway provides a rapid means of response to new antigenic stimuli whereas it is thought that the alternative pathway undergoes constant low-grade, slow turnover
  • C3 component is the pivotal serum protein of the complement system
    • binding of the antigen to C3 results in two possible sequelae
      • in either case, C3 component becomes enzymatically converted to C3b
      • the bacterial cell wall can either remain bound to C3b and become opsonised (since phagocytes have receptors for C3b) or act as a focus for other complement proteins (namely C5, 6, 7, 8 and 9)
        • the latter form the membrane attack complex (MAC), which induces cellular lysis
  • functions of the complement system are therefore
    • opsonisation
    • lysis (destruction of cells through damage/ rupture of plasma membrane)
    • chemotaxis (directed migration of immune cells)
    • initiation of active inflammation via direct activation of mast cells
  • complement is regulated to protect host cells from damage and/or their total destruction
    • achieved by a series of regulatory proteins, which are expressed on the host cells themselves

Deficiency of any component of the complement cascade may lead to a degree of immuno-compromise.