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Immunity by equilibrium

Nature Reviews Immunology volume 16, pages 524–532 (2016)Cite this article

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Abstract

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

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Figure 1: The equilibrium model of immunity.
Figure 2: Tolerance in the equilibrium model of immunity.
Figure 3: Microorganisms in the equilibrium model of immunity.

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Acknowledgements

The author thanks M. Daëron, T. Pradeu, N. Cerf-Bensussan, A. Freitas and B. Marsland for the many discussions, ideas, corrections and critical reading of the manuscript. The author also thanks members of the Microenvironment and Immunity unit of the Institut Pasteur for discussions and experiments over the years that led to the ideas presented in this Essay, as well as the students and postdoctoral researchers of the Department of Immunology of the Institut Pasteur for the Forest seminar series and critical reading of the manuscript.

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  1. Gérard Eberl is at the Institut Pasteur, Microenvironment and Immunity Unit, 75724 Paris, France, and the Institut National de la Santé et de la Recherche Médicale (INSERM) U1224, 75724 Paris, France.,

    Gérard Eberl

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Eberl, G. Immunity by equilibrium. Nat Rev Immunol 16, 524–532 (2016). https://doi.org/10.1038/nri.2016.75

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