Functions of the complement system
Complement has a variety of important functions which includes:
(1) opsonization of antigens: including bacteria by phagocytosis. The complement component, C3b is the major opsonin of the complement system. Phagocytic cells, as well as some other cells, expresscomplement receptors that bind C3b, enhancing phagocytosis by these cells. C3b may also act as an adjuvant when coupled with protein antigens. C3b targets the antigen directly to the phagocyte, enhancing the initiation of antigen processing and accelerating specific antibody production. The coating of soluble immunogen complexes with C3b is thought to facilitate their binding to complement receptors on erythrocytes which carry these complexes to the liver and spleen. In these organs the complexes are stripped away from the red blood cells and phagocytosed. The terminal sequence of complement activation involves a macromolecular structure called MAC which lyses cells. Gram positive bacteria are generally resistant to complement mediated lysis because the thick peptidoglycan layer in their cell wall prevents insertion of the MAC into the inner membrane.
(2) activation of inflammation: The significance of complement activation is not limited to membrane damage resulting from the attack complex. The active complement peptides contribute to the immune response by increasing vascular permeability and contraction of smooth muscle, promoting immune adherence, granulocyte and platelet aggregation, enhancing phagocytosis, and directing the migration of neutrophils (PMN) and macropahges to the site of inflammation.
The cleavage of C3 and C5 results in the release of two small biologically active peptides, C3a and C5a which act as anaphylatoxins. They amplify the immune response by causing the release of histamine, slow releasing substance of anaphylaxis (SRS-A), and heparin from basophils and mast cells. These substances increase capillary permeability and contraction of smooth muscle resulting in edema and inflammation. In addition to its role as an anaphylatoxin, C5a is a potent chemotactic factor which causes the directed migration of leukocytes including DCs and monocytes to the site of inflammation so these leukocytes will phagocytize and clear immune complexes, bacteria and viruses form the system. C5a increases the epxression of complement receptors CR1 and CR3 on both PMN and monocytes and is chemotactic for both types of cells.