Antibodies provide immunity to infection and disease in a variety of ways:
1. They can neutralize the infectivity of a virus, the toxicity of an exotoxin molecule, orthe ability of a bacterium to colonize. This is usually brought about by reaction be-tween the antibody and an epitope that is required for attachment of the organism or toxin to a target host cell. IgA and IgG antibodies are particularly significant in neu-tralizing activity.
2. Antibodies can inhibit essential nutrient assimilation by some bacteria. This occurs when a specific antigenic site or protein is involved in transport of the essential nutri-ent into the cell. For example, some iron-binding siderophores are antigenic, and antibody against them can prevent assimilation of the iron that is essen-tial for growth.
3. Immunoglobulin G antibody can promote phagocytosis of extracellular bacteria by combining with capsules or other surface antigens that otherwise inhibit inges-tion of the organism by phagocytes. When antigen – antibody reactions occur, the attachment sites for phagocytes on the Fc regions of the antibodies are exposed, the organism is bound to the phagocyte, and ingestion occurs. The significance of such opsonization is that many bacteria and some viruses are rapidly destroyed within the phagocytic cell.
4. Antigen – antibody reactions involving IgG and IgM activate the classic pathway of the complement cascade, which is described later. Complement components enhance a wide range of nonspecific host defense mechanisms, synergize antibody-mediated opsonization, and lead to lysis of many Gram-negative bacteria with which antibody has reacted. A similar event occurs with blood and tissue cells carrying surface anti-gens recognized as foreign.
5. Antibodies that recognize foreign antigens on the surface of a host cell, such as a vi-rally infected cell, react with them and can mediate destruction of the cell by the process of antibody-dependent cell-mediated cytotoxicity (ADCC).
In ADCC, the antibodies bind to the cells through their Fc portions that attach to cell surface receptors specific for the Fc regions of particular IgG classes. These are termed Fc receptors (FcR). For example, the human monocyte – macrophage has a plasma membrane receptor that recognizes both IgG1 and IgG3 subclasses through a binding site on the Cg3 domain. Eosinophils have a low-affinity FcR for IgE, which is much lower than that of mast cells. If the antibody is bound by its Fc piece, the Fab regions are free to bind antigen to initiate ADCC in the case of monocytes or polymorphs or an allergic response when IgE molecules on mast cells are cross-linked by binding to the antigen (allergen). A variety of clinical problems arise from this antibody-mediated cytotoxicity, including transfusion re-actions; autoimmune hemolytic anemias; and the autoimmune disease myasthenia gravis, in which antibodies are directed at the acetylcholine receptor in the motor end plate.