The Functions of Complement

Research on complement now includes more than 30 soluble and cell-bound proteins. The biological activities of this system affect both innate and acquired immunity and reach far beyond the original observations of antibody-mediated lysis of bacteria and red blood cells. Structural comparisons of the proteins involved in complement pathways place the origin of this system in primitive organisms possessing the most rudimentary innate immune systems. By contrast, the realization that interaction of cellular receptors with complement proteins controls B-cell activities gives this system a role in the highly developed acquired immune system. Thus we have a system that straddles innate and acquired immunity, contributing to each in a variety of ways.

After initial activation, the various complement components interact, in a highly regulated cascade, to carry out a number of basic functions (Figure 13-1) including:

■ Lysis of cells, bacteria, and viruses

■ Opsonization, which promotes phagocytosis of particulate antigens

■ Binding to specific complement receptors on cells of the immune system, triggering specific cell functions, inflammation, and secretion of immunoregulatory molecules

■ Immune clearance, which removes immune complexes from the circulation and deposits them in the spleen and liver

LYSIS

Complement

Target cell

OPSONIZATION

Bacteria

ACTIVATION OF INFLAMMATORY RESPONSE

Complement receptor

Bacteria

Complement receptor

Clearance Immune Complexes

Phagocyte

CLEARANCE OF IMMUNE COMPLEXES

Ag-Ab nïyj complex

Ag-Ab nïyj complex

Opsonisation Heavy Chain
Phagocyte

Phagocyte

FIGURE 13-1

The multiple activities of the complement system. Serum complement proteins and membrane-bound complement receptors partake in a number of immune activities: lysis of foreign cells by antibody-dependent or antibody-independent pathways; opsonization or uptake of particulate antigens, including bacteria, by phagocytes; activation of inflammatory responses; and clearance of circulating immune complexes by cells in the liver and spleen. Soluble complement proteins are schematically indicated by a triangle and receptors by a semi-circle; no attempt is made to differentiate among individual components of the complement system here.

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