Abstract
Immunology — though deeply experimental in everyday practice — is also a theoretical discipline. Recent advances in the understanding of innate immunity, how it is triggered and how it shares features that have previously been uniquely ascribed to the adaptive immune system, can contribute to the refinement of the theoretical framework of immunology. In particular, natural killer cells and macrophages are activated by transient modifications, but adapt to long-lasting modifications that occur in the surrounding tissue environment. This process facilitates the maintenance of self-tolerance while permitting efficient immune responses. In this Essay we extend this idea to other components of the immune system and we propose some general principles that lay the foundations for a unifying theory of immunity — the discontinuity theory. According to this theoretical framework, effector immune responses (namely, activated responses that lead to the potential elimination of the target antigen) are induced by an antigenic discontinuity; that is, by the sudden modification of molecular motifs with which immune cells interact.
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Acknowledgements
We thank H. Brailly, L. Du Pasquier, J. Ewbank, M. Fougereau, P. Kourilsky, L. Périé, B. Malissen and A. Trautmann for their constructive comments, S. Guia and S. Ugolini for their experimental data on calcium flux, and C. Chapple for his editorial help. E.V.'s laboratory is supported by the European Research Council (THINK Advanced Grant) and by institutional grants from Institut National de la Santé et de la Recherche Médicale, Le Centre national de la recherche scientifique and Aix Marseille to Centre d'Immunologie de Marseille-Luminy. T.P. and E.V. are scholars of the Institut Universitaire de France.
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E.V. is cofounder and shareholder of Innate Pharma, Marseille, France. The other authors declare no conflict of interest.
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Pradeu, T., Jaeger, S. & Vivier, E. The speed of change: towards a discontinuity theory of immunity?. Nat Rev Immunol 13, 764–769 (2013). https://doi.org/10.1038/nri3521
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DOI: https://doi.org/10.1038/nri3521
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