Complement

Complement proteins fall into three broad categories, although some complement proteins may actually fit into two of these categories. The first category encompasses the complement serum proteins, which react with foreign bodies in either an antibody-dependent or antibody-independent manner. The second are regulatory proteins present in serum or on the membranes of host cells. The third are cell surface receptors that bind to the products of complement activation and signal host cells to participate in inflammatory and immune reactions. The complement system is designed to mobilize a large number of immune effector mechanisms when it detects infected or injured self tissues. Three pathways of complement activation are now known: the alternative pathway, the classical pathway, and the lectin pathway. A third pathway of complement activation, the lectin pathway, has recently been defined but, like the alternative pathway of complement activation, likely arose during evolution prior to the classical pathway. Serum opsonins include antibody, complement, fibronectin, and C-reactive protein (CRP). Host phagocytes, such as neutrophils and macrophages, have receptor proteins on their cell surfaces that specifically recognize portions of the antibody molecule (Fc receptors), fragments of complement (C3 receptors), and fibronectin. Immune cells attracted to such sites expose cell surface receptor proteins that recognize particular fragments of C3 and fulfill the biologic function of phagocytosis. Thus, complement constitutes the fundamental proinflammatory response system that can trigger and regulate the remainder of the immune response.