immune tolerance

Immune tolerance permits the immune response to distinguish between self and other, avoiding the problems inherent in autoimmune disorders. Tolerance is either natural or induced.

acquired tolerance : clonal anergy : clonal deletion : hypotheses : idiotype network : induced tolerance : mechanisms : natural tolerance : negative selection : peripheral tolerance : receptor editing : regulatory T, Treg : suppressor population : theories : tolerance in B cells : tolerance in T cells

Several hypotheses have been proposed to explain mechanisms of immunological tolerance:
● Clonal Deletion theory – proposal that self-reactive lymphoid cells are destroyed during the development of the immune system in the individual.
● Clonal Anergy theory, – proposal that self-reactive T- or B-cells become inactivated in the normal individual and cannot amplify the immune response.
● Idiotype Network theory – proposal that a network of antibodies capable of neutralising self-reactive antibodies exists naturally within the body.
● Suppressor population or Regulatory T cell theories – proposal that regulatory T-lymphocytes (commonly including CD4+FoxP3+ cells) function to prevent, downregulate, or limit autoaggressive immune responses.
● Clonal Ignorance theory – proposal that host immune responses are directed to ignore self-antigens.

Induced, or acquired tolerance results from medical manipulations aimed at attenuating the immune or allergic response.
● hyposensitizing, "allergy shots"
● immune suppressant medications to prevent graft rejection
● anti-inflammatory medication to reduce damage wrought by autoimmune disorders

Because some T cells act as helper cells for B cells, it is more efficaceous to induce tolerance in T cell populations. Within the thymus, those maturing T cell precursors that bind self-derived epitope molecules are eliminated by apoptosis. Those comparatively safe T cells that have not been eliminated by this negative selection are released from the thymus to circulate throughout the lymphoid system. Should any T cells with potentially self-attacking TCRs escape thymic control, several back-up mechanisms exist to defuse them:
● lack of a costimulatory signal from "self"-cells
● death signal delivered to T cell by FasL on "self"-cells
suppression of T cells by suppressor, regulatory T cells (Treg)
● sequestered antigens on tissues beyond circulatory barriers

As B cells mature in the bone marrow, tolerance is induced by the process of receptor editingapoptosis of B thymocytes with BCRs directed at self-peptides. Peripheral tolerance is induced in any potential auto-reactive B cells that leave the bone marrow when they fail to receive costimulatory assistance from Th cells.

Tables  Complement Receptors  Cytokines  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors


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. . . since 10/06/06