Complement Components and Pathways

Complement is an exquisitely balanced, highly influential system that is fundamental to the clinical expression of host defense and inflammation. The complement system also has the capacity to perform functions beyond host defense, such as promoting phagocytic removal of dying cells, molecular debris, and weak or superfluous synapses during brain formation. Complement components and receptors function within individual cells and can stabilize intracellular homeostasis. However, complement activation can also cause harm and has been implicated in many illnesses.

The complement system, an essential component of innate and adaptive immunity, is broadly conceptualized as (1) the classical, lectin, and alternative pathways , which interact and depend on each other for their full activity; (2) the membrane attack complex (C5b6789), formed from activity of any pathway; (3) cell membrane receptors that bind complement components or fragments to mediate complement activity; and (4) a large array of serum and membrane regulatory proteins ( Table 159.1 and Fig. 159.1 ). The circulating components and regulators together comprise approximately 15% of the globulin fraction and 4% of the total proteins in serum. The normal concentrations of serum complement components vary by age (see Chapter 748 ); newborn infants have mild to moderate deficiencies of all components.