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Complement pathways

M Kathryn Liszewski, PhD
John P Atkinson, MD
Section Editors
E Richard Stiehm, MD
Peter H Schur, MD
Deputy Editor
Anna M Feldweg, MD


The complement system is an ancient host defense system that traces its biologic origins to more than one billion years ago. It is part of innate and adaptive immunity, and it guards the host's intravascular space by opsonizing and lysing bacteria. In addition, it promotes the local acute inflammatory response, which in turn instructs and influences the adaptive immune response. The complement system consists of plasma proteins of the activating cascades and membrane regulators and receptors. The plasma proteins interact via three major cascades: the classical, alternative, and lectin pathways [1-6].

A review of the complement pathways is presented here. Other discussions of the complement system and its associated diseases, as well as an overview of the innate immune system, are presented separately. (See "Overview and clinical assessment of the complement system" and "Inherited disorders of the complement system" and "Acquired deficiencies of the complement system" and "An overview of the innate immune system".)


Proteins of the complement activation pathways circulate in the plasma and are present at a lower concentration in other body fluids as well as in the intracellular space. The components in plasma are predominantly synthesized in the liver, while the components at other sites represent a combination of local synthesis (many cell types) and filtration from plasma (table 1). (See "Regulators and receptors of the complement system".)


The primary goal of the complement system is the destruction of microbes. This is accomplished through the deposition of large quantities of C3b on a target. This process, known as opsonization, refers to the coating of targets with complement ligands to promote their elimination through immune adherence and phagocytosis by cells bearing complement receptors. Opsonization also facilitates the adaptive immune response including antigen presentation and retention as well as immunologic memory and costimulation of B lymphocytes through the antigen receptor. C3b is partially degraded to iC3b and C3d fragments that also interact with their receptors on phagocytes and immune cells.

A second goal of the complement system is promotion of the inflammatory response, primarily through the liberation of peptides C3a and C5a, known as anaphylatoxins. These approximately 10 kDa peptides bind to their receptors to promote vasodilation, chemotaxis, and other cell activation phenomena.

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Literature review current through: Nov 2017. | This topic last updated: Oct 31, 2016.
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