Complement System: Properties, Components and Activation

Overview of pathways of complement activation

Complement System: Properties, Components and Activation

  • The term complement (C) refers to a system of factors that occurs in normal serum and is activated by antigen-antibody interaction.
  • The complement system belongs to the group of biological effector mechanisms (called triggered enzyme cascades) which also includes coagulation, and the fibrinolytic and kinin systems.

GENERAL PROPERTIES

  • Complement is present in the sera of all mammals. and also in that of most other animals, including birds, amphibians and fish .
  • Complement (C) ordinarily does not bind to free antigens or antibodies but only to antibodies that have combined with their antigens.
  • Various terms such as fixation, binding and consumption have been used to refer to the combination of C with bound immunoglobulin, leading to the activation of the classical C pathway.

COMPONENTS

  • The complement system consists of at least 30 chemically and immunologically distinct serum proteins which make up the complement components, the properdin system and the control proteins.
  • The biological activities of this system affect both innate and acquired immunity far beyond the earlier concept of antibody mediated lysis of bacteria and erythrocytes.
  • Complement is a complex of nine different fractions, C1 to C9.
  • The fraction C1 occurs in serum as a calcium ion-dependent complex, which on chelation with EDTA yields three protein subunits called C1 q, r and s.
  • Thus C is made up of a total of 11 different proteins.
  • C fractions are named C1 to C9 in the sequence of the cascading reaction, except that C4 comes after C1 , before C2.

COMPLEMENT ACTIVATION

  • Complement is normally present in the body in an inactive form but when its activity is induced by antigen antibody combination or other stimuli, C components react in a specific sequence as a cascade.
  • Basically, the C cascade is a series of reactions in which the preceding components act as enzymes on the succeeding components, cleaving them into dissimilar fragments.
  • The larger fragment s usually join the cascade.
  • The smaller fragments which are released often possess biological effects which contribute to defence mechanisms by various basic effector mechanisms including:
    • Lysis of cells and bacteria.
    • Promoting virus neutralisation.
    • Opsonisation, which promotes phagocytosis of particulate antigens.
    • Immune clearance, which removes immune complexes from circulation and deposits them in the spleen and liver.
    • Amplifying the inflammatory process, increasing vascular permeability, inducing smooth muscle contraction and effecting the release of histamine from mast cells.

PATHWAYS

  • The C cascade can be triggered off by three parallel but independent mechanisms or pathways which differ only in the initial steps.
  • Once C3 activation occurs, the subsequent steps are common to all pathways; this is called the classical C pathway, alternative pathway and lectin pathway.
  • The classical pathway is so called because it was the first one identified.
  • It is a more recently evolved mechanism of specific active immunity, while the alternative pathway and lectin pathway represent a more primitive system of non-specific innate immunity.

Overview of pathways of complement activation

Complement System: Properties, Components and Activation

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