immunotolerantsi

Immunotolerance is the state in which the immune system does not mount a response to specific antigens. It encompasses self-tolerance, which prevents autoimmunity against the body's own tissues, and allo-tolerance, which prevents rejection of non-self tissues such as transplanted organs. Natural (central) tolerance develops during immune cell maturation, while induced tolerance can be achieved through deliberate exposure or therapeutic strategies.

Central tolerance occurs through the deletion of self-reactive T cells in the thymus and self-reactive B cells in the bone marrow. Peripheral tolerance involves multiple mechanisms that regulate mature lymphocytes outside primary immune organs, including regulatory T cells that suppress immune responses, clonal anergy where lymphocytes become functionally inactive, clonal deletion via apoptosis, and ignorance or limited antigen exposure. Immune checkpoint pathways, such as CTLA-4 and PD-1, also help maintain tolerance by dampening immune activity.

Examples of tolerance include maternal-fetal tolerance during pregnancy, oral tolerance to food antigens, and mucosal tolerance to commensal microbes. In transplantation, achieving robust immunotolerance would permit graft acceptance without long-term immunosuppression. Approaches under investigation include inducing mixed chimerism, costimulation blockade, and the use of tolerogenic dendritic cells.

Disturbances in immunotolerance can lead to autoimmune diseases, while tumors may exploit tolerance to evade immune destruction. Understanding immunotolerance informs therapies across autoimmunity, transplantation, and cancer, guiding strategies to restore, maintain, or selectively break tolerance as clinically needed.