Release of Sequestered Antigens Can Induce Autoimmune Disease

As discussed in Chapter 10, the induction of self-tolerance in T cells results from exposure of immature thymocytes to self-antigens and the subsequent clonal deletion of those that are self-reactive. Any tissue antigens that are sequestered from the circulation, and are therefore not seen by the developing

T cells in the thymus, will not induce self-tolerance. Exposure of mature T cells to such normally sequestered antigens at a later time might result in their activation.

Myelin basic protein (MBP) is an example of an antigen normally sequestered from the immune system, in this case by the blood-brain barrier. In the EAE model, animals are injected directly with MBP, together with adjuvant, under conditions that maximize immune exposure. In this type of animal model, the immune system is exposed to sequestered self-antigens under nonphysiologic conditions; however, trauma to tissues following either an accident or a viral or bacterial infection might also release sequestered antigens into the circulation. A few tissue antigens are known to fall into this category. For example, sperm arise late in development and are sequestered from the circulation. However, after a vasectomy, some sperm antigens are released into the circulation and can induce auto-antibody formation in some men. Similarly, the release of lens protein after eye damage or of heart-muscle antigens after myocardial infarction has been shown to lead on occasion to the formation of auto-antibodies.

CLINICAL FOCUS

CLINICAL FOCUS

Why Are Women More Susceptible Than Men to Autoimmunity? Gender Differences in Autoimmune Disease

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Responses

  • marcel
    How sequestered antigen leads to auto immunity?
    2 years ago

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