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Maintaining system homeostasis: the third law of Newtonian immunology

Nature Immunology volume 13, pages 902–906 (2012)Cite this article

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Abstract

Because of the potent effector mechanisms of the immune system, the potential for self-destructive immune responses is especially high and many negative regulatory modalities exist to prevent excessive tissue damage. This Commentary places such regulatory mechanisms in the larger context of system organization on many scales. The sometimes counterintuitive nature of feedback control is discussed and a case is made for greater attention to quantitative spatiotemporal aspects of regulation, rather than limiting the discussion to the qualitative descriptions of pathways that dominate at present.

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Figure 1: The effect of tonic suppression on lymphocyte activation in response to signaling input induced by self ligand.

Debbie Maizels

Figure 2: Lymphocyte activation in tissues.

Debbie Maizels

Figure 3: In many signaling systems, a strong stimulus results in strong and rapid induction of negative feedback pathways that quickly suppress the signaling response.

Debbie Maizels

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Acknowledgements

I thank the colleagues with whom I have discussed, over many years, aspects of the ideas presented in this Commentary, and W. Kastenmuller for reading of this manuscript and suggestions for improvements. Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.

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Authors and Affiliations

  1. Ronald N. Germain is in the Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.,

    Ronald N Germain

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  1. Ronald N Germain
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Correspondence to Ronald N Germain.

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Germain, R. Maintaining system homeostasis: the third law of Newtonian immunology. Nat Immunol 13, 902–906 (2012). https://doi.org/10.1038/ni.2404

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