Adaptive Cellular Interactions in the Immune System: The Tunable Activation Threshold and the Significance of Subthreshold Responses

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-11, Vol.89 (21), p.10365-10369
• Main Authors: Grossman, Zvi, Paul, William E.
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antigen presenting cells; Antigens; Autoimmunity; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immune Tolerance; Immunity (Disease); Immunity, Cellular; Immunobiology; Infections; Lymphatic system; Lymphocyte Activation; Lymphocytes; Lymphocytes - immunology; Mathematics; Medical research; Memory; Models, Biological; Molecular excitation; Molecules; Organs and cells involved in the immune response; Signal Transduction; T lymphocytes; Transplantation immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.21.10365

A major challenge for immunologists is to explain how the immune system adjusts its responses to the microenvironmental context in which antigens are recognized. We propose that lymphocytes achieve this by tuning and updating their responsiveness to recurrent signals. In particular, cellular anergy in vivo is a dynamic state in which the threshold for a stereotypic mode of activation has been elevated. Anergy is associated with other forms of cellular activity, not paralysis. Cells engaged in such subthreshold interactions mediate functions such as maintenance of immunological memory and control of infections. In such interactions, patterns of signals are recognized and classified and evoke selective responses. The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions. Autoreactivity is allowed where it is dissociated from uncontrolled aggression.