Adaptive cellular interactions in the immune system: The tunable activation threshold and the significance of subthreshold responses

Z. Grossman, W. E. Paul

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)10365-10369
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number21
DOIs
StatePublished - 1992

Keywords

  • anergy
  • autoreactivity
  • context discrimination
  • memory units

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