The complement system is an enzyme cascade that helps defend against infection. Many complement proteins occur in serum as inactive enzyme precursors (zymogens); others reside on cell surfaces. The complement system bridges innate and acquired immunity by
Complement components have many biologic functions (eg, stimulation of chemotaxis, triggering of mast cell degranulation independent of IgE).
Complement activation: There are 3 pathways of complement activation (see Fig. 3: Complement activation pathways.):
Classical pathway components are labeled with a C and a number (eg, C1, C3), based on the order in which they were identified. Alternative pathway components are often lettered (eg, factor B, factor D) or named (eg, properdin).
Classical pathway activation is Ab-dependent, occurring when C1 interacts with Ag-IgM or aggregated Ag-IgG complexes, or Ab-independent, occurring when polyanions (eg, heparin, protamine, DNA and RNA from apoptotic cells), gram-negative bacteria, or bound C-reactive protein reacts directly with C1. This pathway is regulated by C1 inhibitor (C1-INH). Hereditary angioedema is due to a genetic deficiency of C1-INH.
Lectin pathway activation is Ab-independent; it occurs when mannose-binding lectin (MBL), a serum protein, binds to mannose, fructose, or N-acetylglucosamine groups on bacterial cell walls, yeast walls, or viruses. This pathway otherwise resembles the classical pathway structurally and functionally.
Alternate pathway activation occurs when components of microbial cell surfaces (eg, yeast walls, bacterial cell wall lipopolysaccharide [endotoxin]) or Ig (eg, nephritic factor, aggregated IgA) cleave small amounts of C3. This pathway is regulated by properdin, factor H, and decay-accelerating factor.
The 3 activation pathways converge into a final common pathway when C3 convertase cleaves C3 into C3a and C3b (see Fig. 3: Complement activation pathways.). C3 cleavage may result in formation of the membrane attack complex (MAC), the cytotoxic component of the complement system. MAC causes lysis of foreign cells.
Patients deficient in complement components are often susceptible to recurrent bacterial infections, particularly if the C3 component is absent. Defects in C1 and C4 have been associated with SLE.
Complement components have other immune functions that are mediated by complement receptors (CR) on various cells.
Last full review/revision November 2012 by Peter J. Delves, PhD
Content last modified October 2013