autoimmunity

Autoimmune responses involve immune responses directed at self, and are operative in the development of immunological tolerance to self. Autoimmune diseases arise when the immune system targets the organism's tissues because of a failure of tolerance.

Several hypotheses have been proposed to explain mechanisms of immumological tolerance:
● Clonal Deletion theory – proposal that self-reactive lymphoid cells are destroyed during the development of the immune system in an 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



Tables  Fc receptors  Immune Cytokines  Immunoglobulins  Cell Adhesion Molecules  Cell signaling  Receptor Tyrosine Kinases (RTKs)  Receptor Signal Transduction  Second Messengers 

tags [Immunology][autoimmunity]

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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 editing – apoptosis 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

Immunology
tags [Immunology] [immune tolerance] [immunosuppressants] [hyposensitization]

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