Dynamic tuning of lymphocytes: physiological basis, mechanisms, and function.

@article{Grossman2015DynamicTO,
  title={Dynamic tuning of lymphocytes: physiological basis, mechanisms, and function.},
  author={Zvi Grossman and William E. Paul},
  journal={Annual review of immunology},
  year={2015},
  volume={33},
  pages={
          677-713
        }
}
Dynamic tuning of cellular responsiveness as a result of repeated stimuli improves the ability of cells to distinguish physiologically meaningful signals from each other and from noise. In particular, lymphocyte activation thresholds are subject to tuning, which contributes to maintaining tolerance to self-antigens and persisting foreign antigens, averting autoimmunity and immune pathogenesis, but allowing responses to strong, structured perturbations that are typically associated with acute… 

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References

SHOWING 1-10 OF 127 REFERENCES

Self-tolerance: context dependent tuning of T cell antigen recognition.

TLDR
Autoreactivity and outward-directed immunity are regulated simultaneously and interactively through the interplay of selection, tuning, controlled activation and feedback.

Cellular Tolerance as a Dynamic State of the Adaptable Lymphocyte

TLDR
Progress in the ability to evaluate and manipulate the regulation of immunological tolerance would require a methodology to conjoin many pieces of data together and to look for patterns.

Autoreactivity, dynamic tuning and selectivity.

Balancing immunity and tolerance: deleting and tuning lymphocyte repertoires.

  • C. Goodnow
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
Self-reactive cells are retained with a variety of conditional and potentially flexible restraints, altering susceptibility to autoimmune disease and to infection by genetic or environmental differences either in the way antigens are presented, in the tuning molecules that adjust triggering set points for lymphocyte responses to antigen, or in the effector molecules that eliminate, retain, or expand particular clones.

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

  • Z. GrossmanW. Paul
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1992
TLDR
The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions, and is allowed where it is dissociated from uncontrolled aggression.

Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus.

  • Z. GrossmanA. Singer
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
TLDR
A model in which thymocytes tune their response characteristics individually and dynamically in the course of development is invoked, which begins to explain the mechanisms that link developmental and selection events to each other.

The Impact of T Cell Intrinsic Antigen Adaptation on Peripheral Immune Tolerance

TLDR
Adoptively transferred naïve T cells stably calibrated their responsiveness to a persistent self-antigen in both lymphopenic and T cell–replete hosts, allowing us to examine the unique contribution of adaptation to systemic tolerance.

Dendritic cells control T cell tonic signaling required for responsiveness to foreign antigen

TLDR
It is demonstrated that DCs are specialized cells that not only present foreign antigen, but also promote a “tonic” state in T cells for antigen responsiveness, suggesting that a full DC compartment guarantees optimal T cell responsiveness.
...