Immunological Discrimination between Self and Nonself


Immunological self–nonself discrimination capacity is acquired during lymphopoiesis, formation of mature lymphocytes in the primary lymph organs and during immunopoiesis, the immune responses in the peripheral lymph organs. It rests on specific antigen recognition by B‐ and T cells, but, the innate immune defence system ensures antigen presentation and the delivery, or not, of associated co‐stimulatory signals leading to immune responses or tolerance. Thus both, the acquired and the innate immune defences, play determinant roles in the immunological discrimination. Whether caused by infection or by other factors, alterations of lymphocytes or of antigen presentation can perturb self‐tolerance and trigger autoimmune reactions.

Key Concepts:

  • Self–nonself discrimination rests on both the natural and specific immune defences.

  • During lymphopoiesis, recognition of antigen by immature B‐ or T cells leads to clonal deletion.

  • During immunopoiesis, the development of immune responses or of tolerance largely depends on the cells’ environment leading or not to co‐stimulatory signals.

  • Lymphocytes ensure specific recognition; accessory cells detect internal or external danger signals, emit co‐stimulatory signals and control lymphocyte activation or death.

Keywords: antigen receptors; antigen presentation; clonal deletion; anergy; immunological ignorance; immunological silence; danger model

Figure 1.

Antigens are unable to induce an immune response when given in an inadequate form or in absence of co‐stimulatory signals.

Figure 2.

Antigen, when presented in an adequate form and in presence of adjuvant signals leading to the expression of co‐stimulatory molecules, induces lymphocyte activation, proliferation and differentiation in memory or effector cells.

Figure 3.

The generation of lymphocytes occurs during lympho‐ and immunopoiesis; it leads to central tolerance when the encounter with antigen occurs too early or to peripheral tolerance in absence of adjuvant stimulatory signals.



Janeway CA and Travers P (1996) Immunobiology. New York: Garland.

Karlsen AE and Dyrberg T (1998) Molecular mimicry and self in autoimmunity. Seminars in Immunology 10: 25–34.

Leulier F and Lemaitre B (2008) Toll‐like receptors: taking an evolutionary approach. Nature Reviews. Genetics 6(4): 302–313.

Matzinger P (1998) An innate sense of danger. Seminars in Immunology 10: 43–55.

Moudgil KD and Sercarz EE (2005) Understanding crypticity is the key to revealing the pathogenesis of autoimmunity. Trends in Immunology 26(7): 355–359.

Thellin O and Heinen E (2003) Pregnancy and the immune system: between tolerance and rejection. Toxicology 185: 179–184.

Tsai BY, Lin YL and Chiang BL (2010) Autoimmune response induced by dendritic cells exerts anti‐tumor effect in murine model of leukemia. Journal of Autoimmunity 34(4): 364–370.

Turka LA and Lechler RI (2009) Towards identification of biomarkers of transplantation tolerance. Nature Reviews. Immunology 9(7): 521–526.

Wu Y, Zheng Z, Jiang Y, Chess L and Jiang H (2009) The specificity of T cell regulation that enables self‐nonself discrimination in the periphery. Proceedings of the National Academy of Sciences of the USA 13(106): 534–539.

Further Reading

Bayry J, Thirion M, Delignat S et al. (2004) Dendritic cells and autoimmunity. Autoimmune Reviews 3: 183–187.

Diebold SS (2009) Activation of dendritic cells by toll‐like receptors and C‐type lectins. Handbook of Experimental Pharmacology 188(3): 3–30.

Feurer M, Hill JA, Mathis D and Benoist C (2009) Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nature Immunology 10(7): 689–695.

Mevorach D (2003) Dendritic cells. Modern Aspects in Immunobiology 3: 16.

Read S and Powrie F (2001) CD4(+) regulatory cells. Current Opinions in Immunology 13: 644–649.

Streilin JW (2003) Immune privilege. Modern Aspects of Immunobiology 3: 14.

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

* Required Field

How to Cite close
Defaweux, Valérie, and Heinen, Ernst(Jun 2010) Immunological Discrimination between Self and Nonself. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000899.pub3]