Tolerance: an overview and perspectives

Self tolerance is dependent on mechanisms that operate on T cells and B cells from the earliest stages, that is, from when they first express anti-self-receptors in the primary lymphoid organs of the thymus and bone marrow, all the way through to when they engage with self antigens in the peripheral immune system and within tissues themselves. This continuum of checkpoints and fail-safes ensures that the risk of developing harmful autoimmune diseases remains very small. Certain tissues have a degree of privilege that allows them to mute the immune response against them by mechanisms that are also well represented in cancers. An understanding of the underlying mechanisms of self tolerance is hoped to spawn a new range of therapeutics designed to both reprogram the immune system to avoid long-term intense immunosuppression, and to override the immune system to achieve more effective immunity against cancers and persistent viral infections.