The ability to produce antibodies against non-self (foreign) antigens, while tolerating (not producing antibodies against) self-antigens occurs during the first month or so of postnatal life, when immunological competence is established. If a fetal mouse of one strain receives transplanted antigens from a different strain, therefore, it will not recognize tissue transplanted later in life from the other strain as foreign; consequently, it will not immunologically reject the transplant.
The ability of an individual's immune system to recognize and tolerate self-antigens requires continuous exposure of the immune system to those antigens. If this exposure begins when the immune system is weak—such as in fetal and early postnatal life—tolerance is more complete and long lasting than that produced by exposure beginning later in life. Some self-antigens, however, are normally hidden from the blood, such as thy-roglobulin within the thyroid gland and lens protein in the eye. An exposure to these self-antigens results in antibody produc-
Chapter Fifteen tion just as if these proteins were foreign. Antibodies made against self-antigens are called autoantibodies. Killer T cells that attack self-antigens are called autoreactive T cells.
Although the mechanisms are not well understood, two general theories have been proposed to account for immunological tolerance: clonal deletion and clonal anergy. According to the clonal deletion theory, tolerance to self-antigens is achieved by destruction of the lymphocytes that recognize self-antigens. This occurs primarily during fetal life, when those lymphocytes that have receptors on their surface for self-antigens are recognized and destroyed. There is much evidence for clonal deletion in the thymus, and this mechanism is believed to be largely responsible for T cell tolerance. Anergy (which means "without working") occurs when lymphocytes directed against self-antigens are present throughout life but, for complex and poorly understood reasons, do not attack those antigens. Clonal anergy is believed to be largely responsible for tolerance in B cells, and there is some evidence that it may also contribute to tolerance in T cells.
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