Biological Effects of Complement
The main role of complement is to amplify the humoral immune response. The complement through its various prod-ucts participates in the inflammatory response, opsonization of antigen, viral neutralization, and clearance of immune complexes as follows:
· C5a is a chemotactic molecule specifically recognized by polymorphonuclear leukocytes or phagocytic cells. This substance causes leukocytes to migrate to a tissue in which an antigen–antibody reaction is taking place. At that site, a phagocytic cell recognizes opsonized particles and ingests them.
· C5a not only has a chemotactic effect on neutrophils, but also activates these cells causing their reversible aggregation and release of stored enzymes, including proteases.
· C5a also enhances the adhesiveness of neutrophils to the endothelium.
Complement plays an important role in opsonization of pathogenic bacteria and viruses. Bacteria and viruses are easily phagocytosed by phagocytic cells in the presence of complement component C3b. This is because the receptors for the C3b component are present on the surface of many phagocytes.
Complement participates in type II (cytotoxic) and type III (immune-complex) hypersensitivity reactions. The C3a, C4a, and C5a components stimulate degranulation of mast cells with release of mediators, such as histamine. The C3a frag-ments bind to receptors on basophils and mast cells and induce the release of stored vasoactive amines (e.g., histamine) and heparin. The release of histamine into the tissues results in increased capillary permeability and smooth muscle contrac-tion. Fluid is released into the tissue, thereby causing edema and swelling.
There is some evidence that C3a and C5a may also act directly on endothelial cells, causing increased vascular perme-ability. The end result is very similar to the classical anaphy-lactic reaction that takes place when IgE antibodies bound to the membranes of mast cells and basophils react with the cor-responding antigens. For this reason, C3a and C5a are called as anaphylatoxins.
Complement mediates cytolysis. Insertion of C5b–9 com-plex (MAC) into the cell membrane leads to killing or lysis of erythrocytes, bacteria, and tumor cells. The insertion of the MAC complex results in disruption of the mem-brane, thereby leading to entry of water and electrolytes into the cell.
The binding of C3b to the surface receptors on the activated B cells markedly enhances the production of antibodies in comparison to that of B cells activated by antigen alone. Hence, deficiency of C3b leads to reduced production of antibodies. Therefore, low concentration of both C3b and antibodies affects host defense, resulting in severe pyogenic infections.