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Immunological memory: lessons from the past and a look to the future

Nature Reviews Immunology volume 16, pages 124128 (2016) | Download Citation


Immunological memory is considered to be one of the cardinal features of the adaptive immune system. Despite being a recognized phenomenon since the time of the ancient Greeks, immunologists are yet to fully appreciate the mechanisms that control memory responses in the immune system. Furthermore, our definition of immunological memory itself continues to evolve, with recent suggestions that innate immune cells also show memory-like behaviour. In this Viewpoint article, Nature Reviews Immunology invites five leading immunologists to share their thoughts on our current understanding of the nature of immunological memory. Our experts highlight some of the seminal studies that have shaped the immune memory field and offer contrasting views on the key questions that remain to be addressed.

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Author information


  1. Donna L. Farber is at the Columbia Center for Translational Immunology, Department of Surgery, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA.

    • Donna L. Farber
  2. Mihai G. Netea is at the Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.

    • Mihai G. Netea
  3. Andreas Radbruch is at the Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.

    • Andreas Radbruch
  4. Klaus Rajewsky is at the Immune Regulation and Cancer, Max Delbrück Center for Molecular Medicine in the Helmholtz Alliance, Berlin-Buch 13125, Germany.

    • Klaus Rajewsky
  5. Rolf M. Zinkernagel is at the Institute for Experimental Immunology, University Hospital Zürich, CH-8091 Zürich, Switzerland.

    • Rolf M. Zinkernagel


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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Donna L. Farber or Mihai G. Netea or Andreas Radbruch or Klaus Rajewsky or Rolf M. Zinkernagel.


Germinal centre

A transient, highly organized multicellular structure present within B cell follicles that is a site for the generation of memory B cells and long-lived plasma cells, as well as for affinity maturation of antibodies.


A molecule that can be bound by an antibody but cannot elicit an immune response by itself. Antibodies that are specific for a hapten can be generated when the hapten is chemically linked to a protein carrier that can elicit a T cell response. Haptens have no biological significance, as all relevant determinants of immunity (antigens) involve complex tertiary structures with antibody contact areas of approximately 8–15 amino acids or T cell peptide epitopes of 9–11 amino acids presented by MHC molecules.

Heterologous immunity

Also known as 'infection immunity'. Immunity that develops against a pathogen after the host has been exposed to a non-identical pathogen.

Somatic hypermutation

A programmed process of mutation targeting the variable regions of immunoglobulin genes that allows the selection of B cells that express immunoglobulin receptors with the highest affinity for antigens.

Systemic acquired resistance

(SAR). A state of enhanced immunity to infection in plants that occurs throughout the whole plant after it has been subjected to an initial, localized injury.

Trained immunity

Also referred to as 'innate memory'. The long-term improvement of the function of innate immune cells after infection or vaccination, owing to epigenetic rewiring of cellular functional programmes.

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