Complement is a system of protein molecules, the sequential interactions of which produce biologic effects on surface membranes, on cellular behavior, and on the interactions of other proteins. Each of the proteins of the complement system is inactive by itself. Activation occurs through a cascadelike sequence after contact with substances such as IgG or IgM antigen-antibody complexes, aggregated IgA, certain naturally occurring polysaccharides and lipopolysaccharides, activation products of the coagulation system, and bacterial endotoxins. Activation of the complement system results in an inflammatory response that destroys or damages cells.
Complement proteins are identified by letters and numbers and are listed here in order of activation in the "classical pathway" of the complement cascade: C1q, C1r, C1s, C4, C2, C3, and then C5 through C9. The "alternate pathway" bypasses C1, C4, and C2 activation and begins directly with C3. The key step in the alternate pathway is activation of properdin, a serum protein without biologic effects in its inactive form. Contact with aggregated IgA, with bacterial endotoxins, or with complex molecules such as dextran, agar, and zymosan alters properdin and initiates the sequence at C3.22
Complete activation to C9 leads to membrane disruption and irreversible cell damage. Along the way to complete activation, the following activities occur: C2 releases a low-molecular-weight peptide with kinin activity. Activation of products of C3 and C5 affects mast cells, smooth muscle, and leukocytes to produce an anaphylactic effect; other elements of C3 and C5 bind to cell membranes and render them more susceptible to phagocytosis, a process called opsonization. Fragments of C3 and C4 cause immune adherence, in which complement-coated particles bind to cells with surface membranes that have complement receptors; activated C3 and C4 are also capable of virus neutralization. C3 and C5 exert chemotactic activity on neutrophils, and the C5 to C9 complex influences the procoagulant activity of platelets. Conversely, procoagulant factor XII can initiate C1 activation, and plasmin (the substance that dissolves fibrin) and thrombin (which converts fibrinogen to fibrin) can cleave C3 into its active form.23