Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Real and artificial immune systems: computing the state of the body

Nature Reviews Immunology volume 7, pages 569–574 (2007)Cite this article

Abstract

Here I present the idea that the immune system uses a computational strategy to carry out its many functions in protecting and maintaining the body. Along the way, I define the concepts of computation, Turing machines and system states. I attempt to show that reframing our view of the immune system in computational terms is worth our while.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The universal Turing machine defines computation.
Figure 2: Immune computation.
Figure 3: Natural autoimmunity serves body maintenance.
Figure 4: Reactive animation.

References

  1. Lecture Notes in Computer Science 4163. Artificial Immune Systems. 5 th International Conference, ICARIS 2006. (eds Bersini, H. & Carneiro) (Springer-Verlag, Berlin, 2006).

  2. Stepney, S. et al. Conceptual frameworks for artificial immune systems. Int. J. Unconventional Computing. 1, 315–338 (2005).

    Google Scholar 

  3. Hofmeyr, S. A. & Forrest, S. Architecture for an artificial immune system. Evol. Comput. 8, 443–73 (2000).

    Article  CAS  Google Scholar 

  4. Timmis, J., Neal, M. & Hunt, J. An artificial immune system for data analysis. Biosystems 55, 143–150 (2000).

    Article  CAS  Google Scholar 

  5. Bersini, H. & Carneiro, J. in Lecture Notes in Computer Science 4163. Artificial Immune Systems. 5th International Conference, ICARIS 2006. (eds Bersini H and Carneiro J) Preface (Springer-Verlag, Berlin, 2006).

    Google Scholar 

  6. Perelson, A. S. Modelling viral and immune system dynamics. Nature Rev. Immunol. 2, 28–36 (2002).

    Article  CAS  Google Scholar 

  7. Garrett, S. How do we evaluate artificial immune systems? Evol. Comput. 13, 145–178 (2005).

    Article  Google Scholar 

  8. Harel, D. Computers Ltd.: What They Really Can't Do, Revised paperback edition (Oxford Univ. Press, USA, 2003).

    Google Scholar 

  9. Harel, D. & Feldman, Y . Algorithmics: The Spirit of Computing 3rd edn (Addison-Wesley, 2004).

    Google Scholar 

  10. Ivanov, I. I., Diehl, G. E. & Littman, D. R. Lymphoid tissue inducer cells in intestinal immunity. Curr. Top. Microbiol. Immunol. 308, 59–82 (2006).

    CAS  PubMed  Google Scholar 

  11. Sepehri, S., Kotlowski, R. Bernstein, C. N. & Krause, D. O. Microbial diversity of inflamed and noninflamed gut biopsy tissues in inflammatory bowel disease. Inflamm. Bowel Dis. 13, 675–683 (2007).

    Article  Google Scholar 

  12. Rozenfeld, R. A., Liu, X., DePlaen, I. & Hsueh, W. Role of gut flora on intestinal group II phospholipase A2 activity and intestinal injury in shock. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G957–G963 (2001).

    Article  CAS  Google Scholar 

  13. Schaffer, M., Bongartz, M., Hoffmann, W. & Viebahn, R. MHC-class-II-deficiency impairs wound healing. J. Surg. Res. 138, 100–105 (2007).

    Article  Google Scholar 

  14. Gillitzer, R. & Goebeler, M. Chemokines in cutaneous wound healing. J. Leukoc. Biol. 69, 513–521 (2001).

    CAS  PubMed  Google Scholar 

  15. Ziv, Y., Avidan, H., Pluchino, S., Martino, G. & Schwartz, M. Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury. Proc. Natl Acad. Sci. USA 103, 13174–13179 (2006).

    Article  CAS  Google Scholar 

  16. Zhang, Z. & Schluesener, H. J. Mammalian Toll-like receptors: from endogenous ligands to tissue regeneration. Cell. Mol. Life Sci. 63, 2901–2907 (2006).

    Article  CAS  Google Scholar 

  17. Cursiefen, C. Immune privilege and angiogenic privilege of the cornea. Chem. Immunol. Allergy 92, 50–57 (2007).

    Article  CAS  Google Scholar 

  18. Tettamanti, G. et al. Growth factors and chemokines: a comparative functional approach between invertebrates and vertebrates. Curr. Med. Chem. 13, 2737–2750 (2006).

    Article  CAS  Google Scholar 

  19. Savill, J. Apoptosis in resolution of inflammation. J. Leukoc. Biol. 61, 375–380 (1997).

    Article  CAS  Google Scholar 

  20. Krysko, D. V., D'Herde, K. & Vandenabeele, P. Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11, 1709–1726 (2006).

    Article  Google Scholar 

  21. Cohen, I. R. Discrimination and dialogue in the immune system. Semin. Immunol. 12, 215–9; 321–323 (2000).

    Article  CAS  Google Scholar 

  22. Cohen, I. R. Tending Adam's Garden: Evolving the Cognitive Immune Self (Academic Press, London, UK 2000).

    Google Scholar 

  23. Cohen, I. R. in Lecture Notes in Computer Science 4199 MoDELS 2006, (eds O. Niestrasz et al.) 499–512 (Springer-Verlag, Berlin, 2006).

    Google Scholar 

  24. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. & Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).

    Article  CAS  Google Scholar 

  25. Cohen, I. R. Regen und Auferstehung: Talmud und Naturwissenschaft im Dialog mit der Welt. (Vandenhoek & Ruprecht, Göttingen, Germany 2005).

    Google Scholar 

  26. Kuhn, T. The Structure of Scientific Revolutions, 2nd edn (Univ. Chicago Press, 1970).

    Google Scholar 

  27. Fleck, L. Genesis and Development of a Scientific Fact (Univ. Chicago Press, 1979).

    Google Scholar 

  28. Nobori, S. et al. Thymic rejuvenation and the induction of tolerance by adult thymic grafts. Proc. Natl Acad. Sci. USA 103, 19081–19086 (2006).

    Article  CAS  Google Scholar 

  29. Li, Y., Louzoun, Y. & Weigert, M. Editing anti-DNA B cells by Vlambdax. J. Exp. Med. 199, 337–346 (2004).

    Article  CAS  Google Scholar 

  30. Cabbage, S. E. et al. Regulatory T cells maintain long-term tolerance to myelin basic protein by inducing a novel, dynamic state of T cell tolerance. J. Immunol. 178, 887–896 (2007).

    Article  CAS  Google Scholar 

  31. Cohen, I. R. The cognitive paradigm and the immunological homunculus. Immunol. Today 13, 490–494 (1992).

    Article  CAS  Google Scholar 

  32. Nobrega, A. et al. Global analysis of antibody repertoires. II. Evidence for specificity, self-selection and the immunological 'homunculus' of antibodies in normal serum. Eur. J. Immunol. 23, 2851–2859 (1993).

    Article  CAS  Google Scholar 

  33. Poletaev, A. B. The immunological homunculus (immunculus) in normal state and pathology. Biochemistry Mosc. 67, 600–608 (2002).

    Article  CAS  Google Scholar 

  34. Avrameas, S. Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton'. Immunol. Today 12, 154–159 (1991).

    CAS  PubMed  Google Scholar 

  35. Merbl, Y., Zucker-Toledano, M., Quintana, F. J. & Cohen, I. R. Newborn humans manifest autoantibodies to defined self-molecules detected by antigen microarray informatics. J. Clin. Invest 117, 712–718 (2007).

    Article  CAS  Google Scholar 

  36. Mouthon, L. et al. Invariance and restriction toward a limited set of self-antigens characterize neonatal IgM antibody repertoires and prevail in autoreactive repertoires of healthy adults. Proc. Natl Acad. Sci. USA 92, 3839–3843 (1995).

    Article  CAS  Google Scholar 

  37. Mirilas, P., Fesel, C., Guilbert, B., Beratis, N. G. & Avrameas, S. Natural antibodies in childhood: development, individual stability, and injury effect indicate a contribution to immune memory. J. Clin. Immunol. 19, 109–115 (1999).

    Article  CAS  Google Scholar 

  38. Srivastava, P. Roles of heat-shock proteins in innate and adaptive immunity. Nature Rev. Immunol. 2, 185–194 (2002).

    Article  CAS  Google Scholar 

  39. Abulafia-Lapid, R. et al. T cell proliferative responses of type 1 diabetes patients and healthy individuals to human HSP60 and its peptides. J. Autoimmun. 12, 121–129 (1999).

    Article  CAS  Google Scholar 

  40. Flohe, S. B. et al. Human heat shock protein 60 induces maturation of dendritic cells versus a Th1-promoting phenotype. J. Immunol. 170, 2340–2348 (2003).

    Article  CAS  Google Scholar 

  41. Zanin-Zhorov, A. et al. Heat shock protein 60 enhances CD4+CD25+ regulatory T cell function via innate TLR2 signaling. J. Clin. Invest. 116, 2022–2032 (2006).

    Article  CAS  Google Scholar 

  42. Cohen-Sfady, M. et al. Heat shock protein 60 activates B cells via the TLR4–MyD88 Pathway. J. Immunol. 175, 3594–3602 (2005).

    Article  CAS  Google Scholar 

  43. Amir-Kroll, H. et al. A conjugate vaccine composed of a heat shock protein 60 T-cell epitope peptide (p458) and Neisseria meningitidis type B capsular polysaccharide. Vaccine 24, 6555–6563 (2006).

    Article  CAS  Google Scholar 

  44. Quintana, F. J. & Cohen, I. R. Heat shock proteins as endogenous adjuvants in sterile and septic inflammation. J. Immunol. 175, 2777–2782 (2005).

    Article  CAS  Google Scholar 

  45. Kirwan, S. E. & Burshtyn, D. N. Regulation of natural killer cell activity. Curr. Opin. Immunol. 19, 46–54 (2007).

    Article  CAS  Google Scholar 

  46. Zwirner, N. W., Fuertes, M. B., Girart, M. V., Domaica, C. I. & Rossi, L. E. Cytokine-driven regulation of NK cell functions in tumor immunity: Role of the MICA–NKG2D system. Cytokine Growth Factor Rev. 18, 159–170 (2007).

    Article  CAS  Google Scholar 

  47. Gasser, S., Orsulic, S., Brown, E. J. & Raulet, D. H. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436, 1186–1190 (2005).

    Article  CAS  Google Scholar 

  48. Quintana, F. J., Carmi, P., Mor, F. & Cohen, I. R. DNA fragments of the human 60-kDa heat shock protein (HSP60) vaccinate against adjuvant arthritis: identification of a regulatory HSP60 peptide. J. Immunol. 171, 3533–3541 (2003).

    Article  CAS  Google Scholar 

  49. Cohen, I. R. Peptide therapy for Type I diabetes: the immunological homunculus and the rationale for vaccination. Diabetologia 45, 1468–1474 (2002).

    Article  CAS  Google Scholar 

  50. Quintana, F. J., Carmi, P., Mor, F. & Cohen, I. R. Inhibition of adjuvant-induced arthritis by DNA vaccination with the 70-kd or the 90-kd human heat-shock protein immune cross-regulation with the 60-kd heat-shock protein. Arthritis Rheum. 50, 3712–3720 (2004).

    Article  CAS  Google Scholar 

  51. Oki, Y. et al. Experience with heat shock protein-peptide complex 96 vaccine therapy in patients with indolent non-Hodgkin lymphoma. Cancer 109, 77–83 (2007).

    Article  CAS  Google Scholar 

  52. van Eden. W., van der Zee, R. & Prakken, B. Heat-shock proteins induce T-cell regulation of chronic inflammation. Nature Rev. Immunol. 5, 318–330 (2005).

    Article  CAS  Google Scholar 

  53. Lohse, A. W., Mor, F., Karin, N. & Cohen, I. R. Control of experimental autoimmune encephalomyelitis by T cells responding to activated T cells. Science 244, 820–822 (1989).

    Article  CAS  Google Scholar 

  54. Mimran, A. et al. DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response. J. Clin. Invest. 113, 924–932 (2004).

    Article  CAS  Google Scholar 

  55. Cohen, I. R., Quintana, F. J. & Mimran, A. Tregs in T cell vaccination: exploring the regulation of regulation. J. Clin. Invest. 114, 1227–1232 (2004).

    Article  CAS  Google Scholar 

  56. Zhang, X. Y., Liu, X. G., Wand, W., Wang, W. C. & Gao, X. M. Anti-T-cell humoral and cellular responses in healthy BALB/c mice following immunization with ovalbumin or ovalbumin-specific T cells. Immunol. 108, 465–473 (2003).

    Article  CAS  Google Scholar 

  57. Quintana, F. J. & Cohen, I. R. Anti-ergotypic immunoregulation. Scand. J. Immunol. 64, 205–210 (2006).

    Article  CAS  Google Scholar 

  58. Correale, J., Rojany, M. & Weiner, L. P. Human CD8+ TCR-αβ+ and TCR-γδ+ cells modulate autologous autoreactive neuroantigen-specific CD4+ T-cells by different mechanisms. J. Neuroimmunol. 80, 47–64 (1997).

    Article  CAS  Google Scholar 

  59. Heinemann, M. & Panke, S. Synthetic biology—putting engineering into biology. Bioinformatics 22, 2790–2799 (2006).

    Article  CAS  Google Scholar 

  60. Quintana, F. J. et al. Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes. Proc. Natl Acad. Sci. USA 101 (Suppl. 2), 14615–14621 (2004).

    Article  CAS  Google Scholar 

  61. Quintana, J. F., Merbl, Y., Sahar, E., Domany, E. & Cohen, I. R. Antigen-chip technology for accessing global information about the state of the body. Lupus 15, 428–430 (2006).

    Article  CAS  Google Scholar 

  62. Orimo, A. & Weinberg, R. A. Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 5, 1597–1601 (2006).

    Article  CAS  Google Scholar 

  63. Witz, I. P. Tumor-microenvironment interactions: the selectin–selectin ligand axis in tumor-endothelium cross talk. Cancer Treat. Res. 130, 125–140 (2006).

    Article  CAS  Google Scholar 

  64. Whiteside, T. L. The role of immune cells in the tumor microenvironment. Cancer Treat. Res. 130, 103–124 (2006).

    Article  CAS  Google Scholar 

  65. Tan, T. T. & Coussens, L. M. Humoral immunity, inflammation and cancer. Curr. Opin. Immunol. 19, 209–216 (2007).

    Article  CAS  Google Scholar 

  66. Elaraj, D. M. et al. The role of interleukin 1 in growth and metastasis of human cancer xenografts. Clin. Cancer Res. 12, 1088–1096 (2006).

    Article  CAS  Google Scholar 

  67. Bergmann, C., van Hemmen. J. L. & Segel, L. A. How instruction and feedback can select the appropriate T helper response. Bull. Math. Biol. 64, 425–446 (2002).

    Article  CAS  Google Scholar 

  68. Meier-Schellersheim M., Xu X., Angermann B., Kunkel E. J., Jin T., Germain R.N. Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method. PLoS Comput. Biol. 2, e82 (2006).

    Article  Google Scholar 

  69. Cohen, I. R. & Harel, D. Explaining a complex living system: dynamics, multi-scaling and emergence. J. R. Soc. Interface 4, 175–182 (2007).

    Article  CAS  Google Scholar 

  70. Efroni, S., Harel, D. & Cohen, I. R. Emergent dynamics of thymocyte development and lineage determination. PLoS Comput. Biol. 3, e13 (2007).

    Article  Google Scholar 

Download references

Acknowledgements

I thank my students and colleagues for teaching me about computation and for their stimulating discussions: H. Amir-Kroll, H. Atlan, E. Ben Jacob, H. Bersini, A. Coutinho, E. Domany, S. Efroni, Z. Grossman, D. Harel, Y. Louzoun, M. Meier-Schellersheim, Y. Merbl, F. J. Quintana, A. Sadot, E. Sahar and S. Solomon. The late L. Segel made a unique contribution to my thinking. I thank S. Efroni for helping me prepare figure 4.

Author information

Authors and Affiliations

  1. Irun R. Cohen is at the Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. Irun.cohen@weizmann.ac.il,

    Irun R. Cohen

Authors
  1. Irun R. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Irun Cohen's homepage

Glossary

Algorithm

A 'recipe' for carrying out a computation.

Computation

The process of obtaining a solution to a problem from given inputs by means of an algorithm.

Immunogenic state of the body

The conditions and molecular signals of the body that affect or stimulate the immune system.

Immunological homunculus concept

The concept that the adaptive and innate repertoires of the healthy immune system include receptors that recognize a defined set of body molecules. These self-recognizing receptors combine to encode a functional immune image of key body molecules. The immunological homunculus reads the immunogenic state of the body.

Response state of the immune system

The responses of the immune system to the immunogenic states of the cells and tissues of the body.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cohen, I. Real and artificial immune systems: computing the state of the body. Nat Rev Immunol 7, 569–574 (2007). https://doi.org/10.1038/nri2102

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri2102

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing