selfnonself

Selfnonself is a term used in immunology to describe how the immune system distinguishes the body's own constituents from foreign substances. In classic formulations, self refers to the body's own cells and molecules, while nonself refers to pathogens, transplanted tissue, and other foreign antigens. The selfnonself distinction underpins immune surveillance and the decision to mount an immune response.

Origin and scope: The concept emerged in mid-20th century immunology, associated with the work of Burnet and Medawar, who emphasized that the immune system learns to tolerate self during development. The selfnonself framework has guided thinking in areas such as transplant biology, autoimmunity, and vaccine design, shaping how researchers conceptualize immune reactivity and tolerance.

Mechanisms: Central tolerance in the thymus and bone marrow eliminates self-reactive T and B cells, while peripheral tolerance, regulatory T cells, and anergy prevent autoimmunity. Antigen presentation by MHC molecules helps distinguish self from nonself, directing the activation and expansion of lymphocytes in response to nonself antigens while restraining reactions to self.

Modern refinements: The boundary between self and nonself is not absolute. The danger model, proposed by Matzinger, argues that immune activation depends on danger signals and context rather than nonself status alone. The microbiota, tissue environment, and prior exposure further shape tolerance and responses, complicating a simple dichotomy.

Relevance: The selfnonself framework informs understanding of autoimmune diseases, organ transplantation, allergy, and immunotherapies. While it remains a foundational concept, contemporary immunology emphasizes dynamic tolerance and context-specific responses over a rigid self/nonself dichotomy.