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Adaptation and memory in immune responses

Nature Immunology volume 20, pages 783–792 (2019)Cite this article

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Abstract

Adaptation is the ability of cells, tissues and organisms to rapidly and reversibly modify their properties to maximize fitness in a changing environment. The activity of immune-system components unfolds in the remarkably heterogeneous milieus to which they are exposed in different tissues, during homeostasis or during various acute or chronic pathological states. Therefore, adaptation is essential for immune cells to tune their responses to a large variety of contexts and conditions. The adaptation of immune cells reflects the integration of multiple inputs acting simultaneously or in a temporal sequence, which eventually leads to transcriptional reprogramming and to various functional consequences, some of which extend beyond the duration of the stimulus. A range of adaptive responses have been observed in both adaptive immune cells and innate immune cells; these are referred to with terms such as ‘plasticity’, ‘priming’, ‘training’, ‘exhaustion’ and ‘tolerance’, among others, all of which can be useful for defining a certain immunological process or outcome but whose underlying molecular frameworks are often incompletely understood. Here we review and analyze mechanisms of adaptation and memory in immunity with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.

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Fig. 1: Discriminative properties of adaptation and memory in the immune system.
Fig. 2: Different outputs of immunological adaptations dictated by the properties of the eliciting stimulus.
Fig. 3: Signal-response and signal-integration models of macrophage activation.
Fig. 4: Chromatin control of signal integration in macrophages exposed to synergistic or antagonistic stimuli.

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Acknowledgements

We are grateful to members of the G.N. and R.O. laboratories for scientific discussions and to S. Monticelli for critical reading of the manuscript. Research on related topics in the G.N. laboratory is supported by the European Research Council (ERC Advanced Grant 692789, MEDICI), the European Commission (Consortium grant SYSCYD), the Cariplo Foundation and the Italian Ministry of University and Research (MIUR, grant METRIC (METabolic Regulation of Inflammatory Cells). Research in the R.O. laboratory is supported by grants from the European Research Council (ERC Starting Grant 759532, X-TAM), the Italian Telethon Foundation (SR-Tiget grant award F04), the Italian Ministry of Health (GR-2016-02362156), the Associazione Italiana per la Ricerca sul Cancro (AIRC MFAG, 20247), the Cariplo Foundation (2015–0990) and the European Union (Infect-ERA 126).

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  1. Humanitas University, Pieve Emanuele, Milan, Italy

    Gioacchino Natoli

  2. IRCCS Humanitas, Rozzano, Milan, Italy

    Gioacchino Natoli

  3. San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy

    Renato Ostuni

  4. Vita-Salute San Raffaele University, Milan, Italy

    Renato Ostuni

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Natoli, G., Ostuni, R. Adaptation and memory in immune responses. Nat Immunol 20, 783–792 (2019). https://doi.org/10.1038/s41590-019-0399-9

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