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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.89.21.10365