The complement system

The system of plasma proteins called complement was so-named because it complements the activity of antibody in the lysis of bacteria. It has a central role in host defence against many micro-organisms and in the modulation of inflammatory reactions, an activity that has been illuminated by the study of humans with naturally occurring deficiencies of complement. Complement is activated by three pathways: the classical, alternative and mannan-binding lectin (MBL) pathways (Figure 1 and Table 1). The classical pathway is primarily activated by antibody bound to antigens (immune complexes). The alternative pathway is activated by the direct binding of complement component C3 to pathogens in the absence of antibody. The recently discovered MBL pathway is initiated by the binding of MBL to mannose groups, present on many bacterial cell walls. All three pathways lead to the cleavage of C3, the central component of complement, which functions as an opsonin, tagging pathogens and immune complexes for recognition and uptake, mediated by specific complement receptors on phagocytic cells. Subsequent activation of the terminal complement pathway, known as the membrane attack complex (MAC), leads to cell lysis. An important current focus of complement research is the physiological activities of complement in vivo, on which we will concentrate in this primer.