Neural Nets pp 244-260 | Cite as

Current Paradigms in Immunology

  • Eugenio Cesana
  • Silvia Beltrami
  • Antonia Emanuela Laface
  • Astrid Urthaler
  • Alessandra Folci
  • Alberto Clivio
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3931)


The last decade has seen a revolution in the field of Immunology. Starting from simple views on the ability of the immune system to respond to foreign antigens or to perform self/not-self discrimination, the image has become much more complex, with the realisation that autoreactive lymphocytes normally circulate in the body, without causing harm to the organism. In fact, the critical point in the development of an immune response is the activation of lymphocytes. This depends on the functional state of antigen-presenting cells and on structural features of the so-called “immune synapse”. Self/not-self discrimination is therefore not as strict as previously thought: on the contrary, it has been shown that a certain degree of self-reactivity is useful, if not necessary, to the homeostasis of the organism. Furthermore, the immune system can be viewed as a network of elements which try to connect with each other to avoid death, and are endowed with emerging properties. In this review, we will make a quick summary of the “classical” paradigms in Immunology, and will discuss the dogmas (specificity, self/not-self discrimination, tolerance) as well as the new ideas to explain how the immune system works, all of them emerging from experimental observations made in the last decade of immunological research. All this may have interesting consequences both for immunologists wanting to make mathematical models of the Immune System and for those involved in the use of immune algorithms for the development of “Artificial Immune Systems” and computational applications.


Major Histocompatibility Complex Adaptive Immune System Artificial Immune System Major Histocompatibility Complex Molecule Immunological Synapse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Akira, S., Sato, S.: Toll-like receptors and their signaling mechanisms. Scandinavian Journal of Infectious Diseases 35(9), 555–562 (2003)CrossRefGoogle Scholar
  2. Bankovich, A.J., Girvin, A.T., Moesta, A.K., Garcia, K.: Peptide register shifting within the MHC groove: theory becomes reality. Molecular Immunology 40(14-15), 1033–1039 (2004)CrossRefGoogle Scholar
  3. Bretscher, P., Cohn, M.: A theory of self-nonself discrimination. Science 169(950), 1042–1049 (1970)CrossRefGoogle Scholar
  4. Burnet, F.M.: A modification of Jerne’s theory of antibody production using the concept of clonal selection. Cancer Journal for Clinicians 26(2), 119–121 (1976)CrossRefGoogle Scholar
  5. Cohen, I.R., Hershberg, U., Solomon, S.: Antigen-receptor degeneracy and immunological paradigms. Molecular Immunology 40(14-15), 993–996 (2004)CrossRefGoogle Scholar
  6. Coutinho, A., Haas, W.: In vivo models of dominant T-cell tolerance: where do we stand today? Trends in Immunology 22(7), 350–351 (2001)CrossRefGoogle Scholar
  7. Coutinho, A., Hori, S., Carvalho, T., Caramalho, I., Demengeot, J.: Regulatory T cells: the physiology of autoreactivity in dominant tolerance and quality control of immune responses. Immunological Reviews 182, 89–98 (2001)CrossRefGoogle Scholar
  8. Delon, J., Germain, R.N.: Information transfer at the immunological synapse. Current Biology 10(24), R923-33,-28 (2000)Google Scholar
  9. Edelman, G.M., Gally, J.A.: Degeneracy and complexity in biological systems. Proceedings of the National Academy of Sciences of the United States of America 98(24), 13763–13768 (2001)CrossRefGoogle Scholar
  10. Germain, R.N.: An innately interesting decade of research in immunology. Nature Medicine 10(12), 1307–1320 (2004)CrossRefGoogle Scholar
  11. Haskins, K., Kappler, J., Marrack, P.: The major histocompatibility complex-restricted antigen receptor on T cells. Annual Review of Immunology 2, 51–66 (1984)CrossRefGoogle Scholar
  12. Huppa, J.B., Davis, M.M.: T-cell-antigen recognition and the immunological synapse. Nature Reviews. Immunology. 3(12), 973–983 (2003)CrossRefGoogle Scholar
  13. Jerne, N.: Towards a network theory of the immune system. Annales d’Immunologie 125(1-2), 373–389 (1974)Google Scholar
  14. Kappler, J.W., Roehm, N., Marrack, P.: T cell tolerance by clonal elimination in the thymus. Cell 49(2), 273–280 (1987)CrossRefGoogle Scholar
  15. Krummel, M.F., Davis, M.M.: Dynamics of the immunological synapse: finding, establishing and solidifying a connection. Current Opinion in Immunology 14(1), 66–74 (2002)CrossRefGoogle Scholar
  16. Lanzavecchia, A.: Antigen-specific interaction between T and B cells. Nature 314(6011), 537–539 (1985)CrossRefGoogle Scholar
  17. Mathis, D., Benoist, C.: Back to central tolerance. Immunity, 509–516 (2004)Google Scholar
  18. Matzinger, P.: Tolerance, danger, and the extended family. Annual Review of Immunology 12, 991–1045 (1994)CrossRefGoogle Scholar
  19. Medzhitov, R., Janeway Jr., C.: The Toll receptor family and microbial recognition. Trends in Microbiology 8(10), 452–456 (2000)CrossRefGoogle Scholar
  20. Mellman, I.: Antigen processing and presentation by dendritic cells: cell biological mechanisms. Advances in Experimental Medicine & Biology 560, 63–67 (2005)CrossRefGoogle Scholar
  21. Moretta, L., Bottino, C., Pende, D., Vitale, M., Mingari, M.C., Moretta, A.: Human natural killer cells: Molecular mechanisms controlling NK cell activation and tumor cell lysis. Immunology Letters 100(1), 7–13 (2005)CrossRefGoogle Scholar
  22. Nishimura, E., Sakihama, T., Setoguchi, R., Tanaka, K., Sakaguchi, S.: Induction of antigenspecific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells. International Immunology 16(8), 1189–1201 (2004)CrossRefGoogle Scholar
  23. Park, Y., Moon, Y., Chung, H.Y.: AIRE-1 (autoimmune regulator type 1) as a regulator of the thymic induction of negative selection. Annals of the New York Academy of Sciences 1005, 431–435 (2003)CrossRefGoogle Scholar
  24. Paterson, H.M., Murphy, T.J., Purcell, E.J., Shelley, O., Kriynovich, S.J., Lien, E., Mannick, J.A., Lederer, J.A.: Injury primes the innate immune system for enhanced Toll-like receptor reactivity. Journal of Immunology 171(3), 1473–1483 (2003)CrossRefGoogle Scholar
  25. Shoenfeld, Y.: The idiotypic network in autoimmunity: antibodies that bind antibodies that bind antibodies. Nature Medicine 10(1), 17–18 (2004)CrossRefGoogle Scholar
  26. Skoberne, M., Beignon, A.S., Bhardwaj, N.: Danger signals: a time and space continuum. Trends in Molecular Medicine 10(6), 251–257 (2004)CrossRefGoogle Scholar
  27. Steinman, R.M., Bonifaz, L., Fujii, S., Liu, K., Bonnyay, D., Yamazaki, S., Pack, M., Hawiger, D., Iyoda, T., Inaba, K., Nussenzweig, M.: The innate functions of dendritic cells in peripheral lymphoid tissues. Advances in Experimental Medicine & Biology 560, 83–97 (2005)CrossRefGoogle Scholar
  28. Szyper-Kravitz, M., Zandman-Goddard, G., Lahita, R.G., Shoenfeld, Y.: The neuroendocrineimmune interactions in systemic lupus erythematosus: a basis for understanding disease pathogenesis and complexity. Rheumatic Diseases Clinics of North America 31(1), 161–175 (2005)CrossRefGoogle Scholar
  29. Tonegawa, S., Steinberg, C., Dube, S., Bernardini, A.: Evidence for somatic generation of antibody diversity. Proceedings of the National Academy of Sciences of the United States of America 71(10), 4027–4031 (1974)CrossRefGoogle Scholar
  30. Tracey, K.J.: The inflammatory reflex. Nature 420(6917), 853–859 (2002)CrossRefGoogle Scholar
  31. Varela, F.J., Coutinho, A.: Second generation immune networks. [Review] [59 refs]. Immunology Today 12(5), 159–166 (1991)CrossRefGoogle Scholar
  32. von Boehmer, H.: Mechanisms of suppression by suppressor T cells. Nature Immunology 6(4), 338–344 (2005)CrossRefGoogle Scholar
  33. Zinkernagel, R.M., Doherty, P.C.: Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248(450), 701–702 (1974)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Eugenio Cesana
    • 1
  • Silvia Beltrami
    • 1
  • Antonia Emanuela Laface
    • 1
  • Astrid Urthaler
    • 1
  • Alessandra Folci
    • 1
  • Alberto Clivio
    • 1
  1. 1.Department of Preclinical Sciences, Faculty of MedicineUniversity of MilanoItaly

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