A Discrete Model of Cellular/Humoral Responses

  • R. Puzone
  • B. Kohler
  • P. Seiden
  • F. Celada
Conference paper


The IMMSIM model of the immune system, an automaton that simulates discrete encounters and cell-cell/cell-molecule interactions, has been extended to include both humoral and cell-mediated responses. This article describes and analyses the responses against a family of infective, cytopathic viruses obtained by varying three parameters at random. Depending on the composition of the virus experimental runs end in cure, or death, with differential engagement of the two branches of the immune system, which appear to cooperate but also to compete with each other.


Cellular Automaton Affinity Maturation Free Virus Idiotypic Network Dendritic Antigen Present Cell 
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  1. 1.
    Seidman JG, Leder P (1978). The arrangement and rearrangement of antibody genes. Nature 276:790–795.CrossRefGoogle Scholar
  2. 2.
    Tonegawa S (1983). Somatic generation of antibody diversity. Nature 302:575–581.CrossRefGoogle Scholar
  3. 3.
    Hedrick SM, Cohen DI, Nielsen EA, Davis MM (1983). Isolation of cDNA clones encoding T cell specific membrane-associated proteins. Nature 308:149–153.CrossRefGoogle Scholar
  4. 4.
    Haskins K, Kubo R, White J, Pigeon M, Kappler J, Marrack P (1983). The major histocompatibility complex- restricted antigen receptor on T cells. J. Exp. Med. 157:1149–1162.CrossRefGoogle Scholar
  5. 5.
    Burnet FM (1959). The Clonal Selection Theory of Acquired Immunity. Cambridge University Press (Cambridge). Google Scholar
  6. 6.
    Sprent J, Lo D, Gao EK, Ron Y (1988). T cell selection in the thymus. Immunol. Rev. 101:173–190.CrossRefGoogle Scholar
  7. 7.
    Berzofski JA (1985). The nature and role of antigen processing in T cell activation. In Year in Immunology 1984–1985. Cruse JM, Lewis RE (Eds.). Karger, Basel pp. 18–24.Google Scholar
  8. 8.
    Unanue ER (1984). Antigen-presenting function of the macrophage. Ann. Rev. Immunol. 2:395–428.CrossRefGoogle Scholar
  9. 9.
    Manca F, Kunkl A, Fenoglio D, Fowler A, Sercarz E, Celada F (1985). Constraints in T-B cooperation related to epitope topology on E.coli b-galactosidase. I. The fine specificity of T cells dictates the fine specificity of antibodies directed to conformation-dependent determinants. Eur. J. Immunol. 15:345–350.CrossRefGoogle Scholar
  10. 10.
    Allen PM (1987). Antigen processing at the molecular level. Immunol. Today. 8:270–273.CrossRefGoogle Scholar
  11. 11.
    Lanzavecchia A (1985). Antigen-specific interactions between T and B cells. Nature 314:537–539.CrossRefGoogle Scholar
  12. 12.
    Howard JC (1985). Immunological help at last. Nature 314:494–495.CrossRefGoogle Scholar
  13. 13.
    Celada F (1971). The cellular basis of immunological memory. Prog. Allergy. 15:223–267.CrossRefGoogle Scholar
  14. 14.
    Berek C, Ziegner M (1993). The maturation of the immune response. Immunol. Today. 14:400–404.CrossRefGoogle Scholar
  15. 15.
    Jerne N (1974). Towards a network theory of the immune system. Ann. Inst. Pasteur Immunol. 125C:435–441.Google Scholar
  16. 16.
    De Boer RJ, Perelson AS (1991). Size and connectivity as emergent properties of a developing network. J. Theor. Biol. 149:381–424.CrossRefGoogle Scholar
  17. 17.
    De Boer RJ (1988). Symmetric idiotypic networks. In Theoretical Immunol. (Perelson AS, ed.) Addison-Wesley Publishers (Redwood City, CA) pp. 265–289. Google Scholar
  18. 18.
    Varela FJ, Coutinho A (1991). Second generation immune networks. Immunol. Today 12:159–166.Google Scholar
  19. 19.
    Perelson A, Weisbuch G (1997). Immunology for Physicists, Rev. Modern Physics, 69:1219–1268.CrossRefGoogle Scholar
  20. 20.
    Wolfram S (1996). Theory and applications of Cellular Automata. Addison-Wesley Publishers (Redwood City, CA).Google Scholar
  21. 21.
    Celada F, Seiden P (1992). A computer model of cellular interactions in the immune system, Immunol. Today. 13:56–62.CrossRefGoogle Scholar
  22. 22.
    Seiden P, Celada F (1992). A model for simulating cognate recognition and response in the immune system. J. Theor. Immunol. 158:329–357.Google Scholar
  23. 23.
    Celada F, Seiden P (1996). Affinity maturation and hypermutation in a simulation of the humoral immune response. Europ. J. Immunol. 26:1350–1358.CrossRefGoogle Scholar
  24. 24.
    Stewart J. Agosto H, Litwin S, Welsh JD, Schlomchik M, Wiegert M, Seiden P (1997). A solution to the rheumatoid factor paradox. J. Immunol. 159:1728–1738.Google Scholar
  25. 25.
    Kohler B, Puzone R, Seiden P, Celada F (2000). A systematic approach to vaccine complexity using an automaton model of the cellular and humoral immune system. Vaccines (in press)Google Scholar

Copyright information

© Springer-Verlag London Limited 2001

Authors and Affiliations

  • R. Puzone
    • 1
  • B. Kohler
    • 2
  • P. Seiden
    • 3
  • F. Celada
    • 2
    • 4
  1. 1.Nat. Inst. Cancer ResearchGenoaItaly
  2. 2.Hospital for Joint DiseasesNYUNew YorkUSA
  3. 3.IBM Research CenterYorktown HeightsUSA
  4. 4.University of GenoaItaly

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