- Peripheral tolerance
Peripheral tolerance is immunological tolerance developed after T and B cells mature and enter the periphery. The cells are controlled through peripheral tolerance mechanisms. These include the suppression of autoreactive cells by 'regulatory' T cells and the generation of hyporesponsiveness (anergy) in lymphocytes which encounter antigen in the absence of the co-stimulatory signals that accompany inflammation.
Potentially self-reactive T-cells are not activated at immunoprivileged sites, where antigens are expressed in non-surveillanced areas. This can occur in the testes, for instance.
Some antigens are at too low a concentration to cause an immune response - a subthreshold stimulation will lead to apoptosis in a T cell.
As many pathways of immunity are interdependent, they do not all need to be tolerised. For example, tolerised T cells will not activate autoreactive B cells. Without this CD4+ T-cell help the B cells will not be activated.
T-cells can be made non-responsive to antigens presented if the T-cell engages an MHC molecule without co-stimulatory molecules. This will occur if there is no acute inflammation, leading to no co-stimulator upregulation due to the low concentration of cytokines.
Auto-reactive T-cells are prevented from reacting due to the presence of T-reg cells. Experimentally, removal of T-reg cells leads to autoimmune attack.
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