Immune tolerance

Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen^[1][2] and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.

Immune tolerance is important for normal physiology and homeostasis. Central tolerance is crucial for enabling the immune system to differentiate between self and non-self antigens, thereby preventing autoimmunity. Peripheral tolerance plays a significant role in preventing excessive immune reactions to environmental agents, including allergens and gut microbiota. Deficiencies in either central or peripheral tolerance mechanisms can lead to autoimmune diseases, with conditions such as systemic lupus erythematosus,^[3] rheumatoid arthritis, type 1 diabetes,^[4] autoimmune polyendocrine syndrome type 1 (APS-1),^[5] and immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX)^[6] as examples. Furthermore, disruptions in immune tolerance are implicated in the development of asthma, atopy,^[7] and inflammatory bowel disease.^[4]

In the context of pregnancy, immune tolerance is vital for the gestation of genetically distinct offspring, as it moderates the alloimmune response sufficiently to prevent miscarriage.

However, immune tolerance is not without its drawbacks. It can permit the successful infection of a host by pathogenic microbes that manage to evade immune elimination.^[8] Additionally, the induction of peripheral tolerance within the local microenvironment is a strategy employed by many cancers to avoid detection and destruction by the host's immune system.^[9]