Tolerance of the Acquired Immunity System to One’s Own Tissues - Role of Preprocessing in the Thymus and Bone Marrow
If a person should become immune to his or her own tissues, the process of acquired immunity would destroy the individual’s own body. The immune mech-anism normally “recognizes” a person’s own tissues as being distinctive from bacteria or viruses, and the person’s immunity system forms few antibodies or activated T cells against his or her own antigens.
Most Tolerance Results from Clone Selection During Prepro-cessing. It is believed that most tolerance developsduring preprocessing of T lymphocytes in the thymus and of B lymphocytes in the bone marrow. The reason for this belief is that injecting a strong antigen into a fetus while the lymphocytes are being preprocessed in these two areas prevents development of clones of lymphocytes in the lymphoid tissue that are specific for the injected antigen. Experiments have shown that specific immature lymphocytes in the thymus, when exposed to a strong antigen, become lymphoblastic, proliferate considerably, and then combine with the stimulating antigen—an effect that is believed to cause the cells themselves to be destroyed by the thymic epithelial cells before they can migrate to and colonize the total body lymphoid tissue.
It is believed that during the preprocessing of lym-phocytes in the thymus and bone marrow, all or most of those clones of lymphocytes that are specific to damage the body’s own tissues are self-destroyed because of their continual exposure to the body’s antigens.
Failure of the Tolerance Mechanism Causes Autoimmune Dis-eases. Sometimes people lose their immune toleranceof their own tissues. This occurs to a greater extent the older a person becomes. It usually occurs after destruc-tion of some of the body’s own tissues, which releases considerable quantities of “self-antigens” that cir-culate in the body and presumably cause acquired immunity in the form of either activated T cells or antibodies.
Several specific diseases that result from autoim-munity include (1) rheumatic fever, in which the body becomes immunized against tissues in the joints and heart, especially the heart valves, after exposure to a specific type of streptococcal toxin that has an epitope in its molecular structure similar to the structure of some of the body’s own self-antigens; (2) one type of glomerulonephritis, in which the person becomesimmunized against the basement membranes of glomeruli; (3) myasthenia gravis, in which immunity develops against the acetylcholine receptor proteins of the neuromuscular junction, causing paralysis; and (4) lupus erythematosus, in which the person becomesimmunized against many different body tissues at the same time, a disease that causes extensive damage and often rapid death.
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