Immunological tolerance and autoimmunity

Sergio Romagnani

Immunological tolerance is a complex series of mechanisms that impair the immune system to mount responses against self antigens. Central tolerance occurs when immature lymphocytes encounter self antigens in the primary lymphoid organs, and consequently they die or become unreactive. Peripheral tolerance occurs when mature lymphocytes, escaped from negative selection during ontogeny, encounter self antigens in secondary lymphoid organs and undergo anergy, deletion or suppression. A heterogeneous family of T regulatory cells has recently been identified, which have been found to play an important role in suppressing immune responses against self. Failure or breakdown of immunological tolerance results in autoimmunity and autoimmune diseases. Such events are related to both genetic and environmental factors, the latter being mainly represented by infections. Infectious agents can indeed promote autoimmune responses either by inducing tissue inflammation and therefore an unintended bystander activation of autoreactive T cells, or by promoting T cell responses to microbial epitopes that cross react against self peptides.