The presence of immune responses against self-tissues/cells
Pathophysiology
Autoreactive B and T cells are generated normally in primary lymphoid tissues but are normally killed/inactivated by ‘tolerance’ mechanisms
Central tolerance: deletion of self-reactive lymphocytes in primary lymphoid tissues
Peripheral tolerance: inactivation of self-reactive lymphocytes in peripheral tissues that escapes central tolerance e.g. by TREG cells
Genetic contribution
IPEX syndrome - X linked mutation in the FOXP3 gene (involved in TREG development)
HLA genes encode for MHC cells - several HLA alleles have been identified which predispose individuals to autoimmune diseases
Nearly all autoimmune diseases are more common in females due to hormonal influences
Environmental contribution
Infection → cross-reactivity (molecular mimicry)
Alteration of self-antigens e.g. due to conjugation of self-antigens with products of drug/chemical metabolism
Super-antigens - bacteria responsible for toxic shock can reactivate autoreactive T cells which have been inactivated by TREG cells
Antigen sequestration - antigens in tissues that do not normally communicate with blood/lymph (e.g. eye, brain) can be exposed due to trauma, causing an autoimmune reaction
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