The Complement System / Cascade

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The complement system or complement cascade as it is also known is a complex system of multiple proteins involved in inflammation and immunological response. The components of the complement system can be found throughout the body in fluids, providing the body with a systemic means of protection. Antibodies depend on complement for many of their biological activities.

Why is complement important?

  • It opsonises pathogens to promote phagocytosis by phagocytes which display receptors for complement
  • Certain components of complement act as good chemoattractants recruiting and activating phagocytes at the site of infection
  • Complement structures can cause cytolysis or damage to certain bacteria by puncturing their membrane

The important protein components of complement are number C1 to C9 (they are numbered in their order of discovery however and not their order of action as you will see later). Upon activation certain components may split into sub components, usually the small components are named with an ‘a’ e.g. C5a (these are the components which are able to diffuse through tissue readily) and the larger components with a ‘b’ e.g. C5b (these are the components which do not easily diffuse).

The complement system is known as a cascade because of the triggering and amplification of further components of the system. In the cascade once a component has been activated by a proteinase, the molecule itself which was activated becomes a proteinase for the next component of the cascade. The whole complement cascade can be triggered in its entirety in a matter of microseconds. During the activation process the smaller ‘a’ subcomponent peptides which are formed mediate many of the other effects caused by the complement cascade, for example acting as chemoattractants.

There are three types of complement cascade, the classical and alternative pathways and the Mannan-binding lectin pathway. Both provide a path to the cleavage of C3 which is a central event in complement activation.

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