Immunological Memory


Immunological memory is a distinct characteristic of the immune system and it relates to its ability to remember antigens on pathogens, tumour cells, tissue of the immunological self, and cells and tissues derived from other individuals of the species and mount an immunological response of greater magnitude and with faster kinetics upon re‐encounter of the same antigens. This property provides an advantage in the course of protective responses against pathogens and tumour cells, but represents a threat in the case of allogeneic cell or tissue transplant. During the past decade considerable progress has been made in the elucidation of the multiple cellular and molecular mechanisms regulating the induction and maintenance of immunological memory. Although our understanding remains imperfect, the current cumulative information allows one to recognise operational patterns and identify those principles that will aid in the design of better vaccines and better understanding the role of immune system in protection against disease.

Key Concepts:

  • Immunological memory represents an important aspect of the immune response in mammals.

  • Immunological memory exists for both B lymphocytes (antibody producing cells) and for T cells.

  • Memory responses by the immune system occur according to only partially understood operational principles.

  • Memory responses form the basis for the effectiveness of vaccines against pathogens and cancer cells.

  • Memory responses protect the individual and the species against the threat of pathogens and cancer cells.

Keywords: immunological memory; B cells; T cells; germinal centre; memory B cells; effector memory T cells; central memory T cells; stem cell‐like memory T cells

Figure 1.

Dynamic view of the generation of memory B lymphocytes following the germinal center (GC) reaction. CD45RO (RO) and CD45RO+ (RO+) lymphocytes in GC are seen in relationship with somatic hypermutation. An inverse relationship exists for RO and RO+ B lymphocytes with respect to AID activity and cell proliferation (Ki67 positivity), whereas CD69 positivity (activation) increases, as cells become RO+. Memory (M) B cells derive from RO+ cells. Reproduced from Zanetti , with permission from American Society of Hematology.

Figure 2.

Schematic representation of the two main phases of the primary expansion leading into a long‐term response waiting to re‐encounter antigen. The programming and post‐programming phases, and their relationship with maintenance and homoeostatic proliferation are shown.

Figure 3.

Development and persistence of serum antibody and, generation and maintenance of immunological memory following one dose of noninfectious poliovirus vaccine. Reproduced from Zanetti et al. , with permission from Elsevier.



Akbar AN, Beverley PC and Salmon M (2004) Will telomere erosion lead to a loss of T‐cell memory? Nature Reviews Immunology 4: 737–743.

Almanza G, Fernandez A, Volinia S et al. (2010) Selected microRNAs define cell fate determination of murine central memory CD8T cells. PLoS One 5: e11243.

Bannard O, Kraman M and Fearon DT (2009) Secondary replicative function of CD8+ T cells that had developed an effector phenotype. Science 323: 505–509.

Bernasconi NL, Traggiai E and Lanzavecchia A (2002) Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298: 2199–2202.

Berner V, Liu H, Zhou Q et al. (2007) IFN‐gamma mediates CD4+ T‐cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nature Medicine 13: 354–360.

Chapuis AG, Thompson JA, Margolin KA et al. (2012) Transferred melanoma‐specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype. Proceedings of the National Academy of Sciences of the USA 109: 4592–4597.

Clark EA and Ledbetter JA (1994) How B and T cells talk to each other. Nature 367: 425–428.

Cui W and Kaech SM (2010) Generation of effector CD8+ T cells and their conversion to memory T cells. Immunological Reviews 236: 151–166.

Day CL, Kaufmann DE, Kiepiela P et al. (2006) PD‐1 expression on HIV‐specific T cells is associated with T‐cell exhaustion and disease progression. Nature 443: 350–354.

Fritsch RD, Shen X, Sims GP et al. (2005) Stepwise differentiation of CD4 memory T cells defined by expression of CCR7 and CD27. Journal of Immunology 175: 6489–6497.

Garside P, Ingulli E, Merica RR et al. (1998) Visualization of specific B and T lymphocyte interactions in the lymph node. Science 281: 96–99.

Gattinoni L, Lugli E, Ji Y et al. (2011) A human memory T cell subset with stem cell‐like properties. Nature Medicine 17: 1290–1297.

Gattinoni L, Zhong XS, Palmer DC et al. (2009) Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nature Medicine 15: 808–813.

Germain RN, Robey EA and Cahalan MD (2012) A decade of imaging cellular motility and interaction dynamics in the immune system. Science 336: 1676–1681.

Goldrath AW, Sivakumar PV, Glaccum M et al. (2002) Cytokine requirements for acute and basal homeostatic proliferation of naive and memory CD8+ T cells. Journal of Experimental Medicine 195: 1515–1522.

Gray D and Matzinger P (1991) T cell memory is short‐lived in the absence of antigen. Journal of Experimental Medicine 174: 969–974.

Huang LR, Chen FL, Chen YT, Lin YM and Kung JT (2000) Potent induction of long‐term CD8+ T cell memory by short‐term IL‐4 exposure during T cell receptor stimulation. Proceedings of the National Academy of Sciences of the USA 97: 3406–3411.

Jackson SM, Harp N, Patel D et al. (2007) CD45RO enriches for activated, highly mutated human germinal center B cells. Blood 110: 3917–3925.

Jacob J and Baltimore D (1999) Modelling T‐cell memory by genetic marking of memory T cells in vivo. Nature 399: 593–597.

Jameson SC (2002) Maintaining the norm: T‐cell homeostasis. Nature Reviews Immunology 2: 547–556.

Janssen EM, Droin NM, Lemmens EE et al. (2005) CD4+ T‐cell help controls CD8+ T‐cell memory via TRAIL‐mediated activation‐induced cell death. Nature 434: 88–93.

Janssen EM, Lemmens EE, Wolfe T et al. (2003) CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421: 852–856.

Joshi NS, Cui W, Chandele A et al. (2007) Inflammation directs memory precursor and short‐lived effector CD8(+) T cell fates via the graded expression of T‐bet transcription factor. Immunity 27: 281–295.

Kaech SM and Ahmed R (2001) Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nature Immunology 2: 415–422.

Kaech SM, Wherry EJ and Ahmed R (2002) Effector and memory T‐cell differentiation: implications for vaccine development. Nature Reviews Immunology 2: 251–262.

Kearney ER, Pape KA, Loh DY and Jenkins MK (1994) Visualization of peptide‐specific T cell immunity and peripheral tolerance induction in vivo. Immunity 1: 327–339.

Lam KP, Kuhn R and Rajewsky K (1997) In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90: 1073–1083.

Lanzavecchia A, Bernasconi N, Traggiai E et al. (2006) Understanding and making use of human memory B cells. Immunological Reviews 211: 303–309.

Lau LL, Jamieson BD, Somasundaram T and Ahmed R (1994) Cytotoxic T‐cell memory without antigen. Nature 369: 648–652.

Manjunath N, Shankar P, Wan J et al. (2001) Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. Journal of Clinical Investigation 108: 871–878.

Markiewicz MA, Girao C, Opferman JT et al. (1998) Long‐term T cell memory requires the surface expression of self‐peptide/major histocompatibility complex molecules. Proceedings of the National Academy of Sciences of the USA 95: 3065–3070.

Maruyama M, Lam KP and Rajewsky K (2000) Memory B‐cell persistence is independent of persisting immunizing antigen. Nature 407: 636–642.

Muramatsu M, Kinoshita K, Fagarasan S et al. (2000) Class switch recombination and hypermutation require activation‐induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553–563.

Pipkin ME, Sacks JA, Cruz‐Guilloty F et al. (2010) Interleukin‐2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32: 79–90.

Sallusto F, Geginat J and Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annual Review of Immunology 22: 745–763.

Sanz I, Wei C, Lee FE and Anolik J (2008) Phenotypic and functional heterogeneity of human memory B cells. Seminars in Immunology 20: 67–82.

Schluns KS and Lefrancois L (2003) Cytokine control of memory T‐cell development and survival. Nature Reviews Immunology 3: 269–279.

Sharpe AH, Wherry EJ, Ahmed R and Freeman GJ (2007) The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nature Immunology 8: 239–245.

Slifka MK, Antia R, Whitmire JK and Ahmed R (1998) Humoral immunity due to long‐lived plasma cells. Immunity 8: 363–372.

Tanchot C, Lemonnier FA, Perarnau B, Freitas AA and Rocha B (1997) Differential requirements for survival and proliferation of CD8 naive or memory T cells. Science 276: 2057–2062.

Tew JG, Phipps RP and Mandel TE (1980) The maintenance and regulation of the humoral response: persisiting antigen and the role of follicular antigen‐binding dendritic cells as accessory cells. Immunological Reviews 53: 175–201.

Vaccari M, Trindade CJ, Venzon D, Zanetti M and Franchini G (2005) Vaccine‐induced CD8+ central memory T cells in protection from simian AIDS. Journal of Immunology 175: 3502–3507.

Weninger W, Crowley MA, Manjunath N and von Andrian UH (2001) Migratory properties of naive, effector, and memory CD8(+) T cells. Journal of Experimental Medicine 194: 953–966.

Wherry EJ, Teichgraber V, Becker TC et al. (2003) Lineage relationship and protective immunity of memory CD8 T cell subsets. Nature Immunology 4: 225–234.

Williams MA, Tyznik AJ and Bevan MJ (2006) Interleukin‐2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature 441: 890–893.

Wrammert J, Smith K, Miller J et al. (2008) Rapid cloning of high‐affinity human monoclonal antibodies against influenza virus. Nature 453: 667–671.

Zanetti M (2007) Gating on germinal center B cells. Blood 110: 3816–3817.

Zanetti M, Sercarz E and Salk J (1987) The immunology of new generation vaccines. Immunology Today 8: 18–25.

Zaph C, Uzonna J, Beverley SM and Scott P (2004) Central memory T cells mediate long‐term immunity to Leishmania major in the absence of persistent parasites. Nature Medicine 10: 1104–1110.

Further Reading

Ahmed R and Gray D (1996) Immunological memory and protective immunity: understanding their relation. Science 272: 54–60.

Crotty S (2011) Follicular helper CD4 T cells (TFH). Annual Review of Immunology 29: 621–663.

Zanetti M and Franchini G (2006) T cell memory and protective immunity. Is more better? Trends in Immunology 27: 511–517.

Zanetti M and Schoenberger S (eds) (2010) Memory T cells ISBN: 978‐1‐4419‐6450‐2. Austin, Texas: Landes Bioscience Publisher.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Zanetti, Maurizio(Feb 2013) Immunological Memory. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000951.pub3]