S Ballotti | PubMed Health

PubMed2006

Autoimmunity: basic mechanisms and implications in endocrine diseases. Part I.

Autoimmunity implies disturbances at several levels of the immune control. Self-tolerance and discrimination between self and non-self synergize to avoid the development of autoimmunity. Negative selection in the thymus, the transcription factor AIRE, CD4+CD25+ regulatory T cells, and dendritic cells cooperate to produce and maintain tolerance. Cytokines modulate deriving immune processes and influence the local micro-environment. Multiple mechanisms are involved in tolerance breakdown: genetic factors (major histocompatibility complex haplotypes, polymorphisms in the cytotoxic T lymphocyte antigen gene and epigenetic alterations), environmental factors (mainly infections), impaired apoptosis, and the emergence of autoreactive naive lymphocytes. These events may be involved in the pathogenesis of endocrine diseases at several levels.

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PubMed2006

Autoimmunity: basic mechanisms and implications in endocrine diseases. Part II.

Regulation of the immune response to self-antigens is a complex process that involves maintaining self-tolerance while preserving the capacity to exert an effective immune response. The primary mechanism that leads to self-tolerance is central tolerance. However, potential pathogenic autoreactive lymphocytes are normally present in the periphery of all individuals. This suggests the existence of mechanisms of peripheral tolerance that prevent the initiation of autoimmune diseases by limiting the activation of autoreactive lymphocytes. If these mechanisms of peripheral tolerance are impaired, the autoreactive lymphocytes may be activated and autoimmune diseases can develop. Several processes are involved in the maintenance of peripheral tolerance: the active suppression mediated by regulatory T cell populations, the different maturation state of antigen-presenting cells presenting the autoantigen to autoreactive lymphocytes, inducing tolerance instead of cell activation, the characteristics of B cell populations. A deeper comprehension of these mechanisms may lead to important therapeutic applications, such as the development of cellular vaccines for organ-specific autoimmune diseases. In addition, autoimmunity does not always have pathological consequences, but may exert a protective function, as suggested by several observations on the beneficial role of autoreactive T cells in central nervous system injury.

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