When HIV Meets the Immune System: Network Theory, Alloimmunity, Autoimmunity, and AIDS

  • Geoffrey W. Hoffmann
  • Michael D. Grant
Part of the Lecture Notes in Biomathematics book series (LNBM, volume 83)

Abstract

It is suggested that the following facts are relevant to AIDS pathogenesis. Firstly, there is complementarity of the AIDS virus envelope glycoprotein gpl20 to a molecule on helper T cells called the CD4 protein, and there is also complementarity of CD4 to certain molecules that are important in the immune system, namely class IIMHC. In this respect, gp120 is similar to class II MHC, and the anti-viral immune response may include a component that is directed against class II MHC or V regions resembling class II MHC. Secondly, immunization with foreign lymphocytes can lead to the production of antibodies with V regions that resemble MHC proteins. Since infection with HIV often occurs coincidentally with exposure to allogeneic lymphocytes, infected individuals are likely to make such MHC mimicking antibodies. These facts lead to the idea that AIDS is an autoimmune disease that can be triggered by a combination of HIV and allogeneic cells. These two stimuli would produce mutually complementary “MHC-image” and anti-(MHC image) immune responses that could synergize with each other and destabilize the system. We discuss some recent experimental results on autoantibodies found in AIDS patients and in persons at risk for AIDS that support these ideas.

The theory suggests that vaccines consisting of gp120 or some related substances may cause AIDS in people belonging to high risk groups. It also leads to new experimentally testable predictions and ideas for preventing the disease. For example, we may be able to prevent AIDS using injections of the viral envelope glycoprotein (gp120 or gp160) together with anti-gp120 or anti-gp160.

Further progress may come from a more detailed understanding of the immune system network. A mathematical model of the symmetrical network theory is reviewed briefly.

Keywords

Galle Encephalomyelitis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andrieu, J.M., P. Even, and A. Venet. (1986). AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications. AIDS Research 2, 163–174.CrossRefGoogle Scholar
  2. Beretta, A., F. Grassi, M. Pelagi, A. Clivio, C. Parravicini, G. Giovinazzo, F. Andronico, L. Lopalco, P. Verani, S. Butto, F. Titti, G. Battista Rossi, E. Ginelli, and A.G. Siccardi. (1987). HIV env glycoprotein shares a cross-reacting epitope with a surface protein present on activated human monocytes and involved in antigen presentation. Eur. J. Immunol 17, 1793–1798.CrossRefGoogle Scholar
  3. Borsos, T. and H.J. Rapp. (1965). Complement fixation on cell surfaces by 19S and 7S antibodies. Science 150, 505–506.CrossRefGoogle Scholar
  4. Davis, M.M. and P.J. Bjorkman. (1988). T cell antigen receptor genes and T cell recognition. Nature 334, 395–402. Fitch, F.W. (1975). Selective suppression of immune responses. Regulation of antibody formation and cell-mediated immunity by antibody. Prog. Allergy 19, 195–244.Google Scholar
  5. Grant, M.D., M.S. Weaver, C. Tsoukas, and G.W. Hoffmann. (1989). Distribution of antibodies against denatured collagen in AIDS risk groups and homosexuals AIDS patients suggests a link between autoimmunity and the immunopathogenesis of AIDS. Submitted to J. Immunol. Google Scholar
  6. Harper, M.E., L.M. Marselle, R.C. Gallo, and F. Wongstaal. (1986). Detection of lymphocytes expressing human lymphotropic-T virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc. Nat. Acad. Sci. (USA) 83, 772–776.CrossRefGoogle Scholar
  7. Henry, C. and Jerne, N.K. (1968). Competition of 19S and 7S antigen receptors on the regulation of the primary immune response. J. exp. Med. 128, 133–152.CrossRefGoogle Scholar
  8. Hoffmann, G.W. (1980). On network theory and H-2 restriction. Contemp. Topics in Immunobiol. 11, 185–226.Google Scholar
  9. Hoffmann, G.W. (1982). The application of stability criteria to the evaluation of network regulation models. In Regulation of Immune Response Dynamics, C. DeLisi and J. Hiernaux (eds.), pp. 137–162, CRC Press, Boca Raton, Florida.Google Scholar
  10. Hoffmann, G.W., A. Cooper-Willis, and M. Chow (1986). A new symmetry: A anti-B is anti-(B anti-A), and reverse enhancement. J. Immunol 137, 61–68.Google Scholar
  11. Hoffmann, G.W., T.A. Kion, R.B. Forsyth, K.G. Soga, and A. Cooper-Willis. (1988). The N-dimensional network. In Theoretical Immunology, Part 2, A. S. Perelson, (ed.), pp. 291–319, Addison-Wesley, Redwood City CA.Google Scholar
  12. Hoffmann, G.W. (1988). On I-J, a network centre pole and AIDS. In The Semiotics of Cellular Communication in the Immune System, E. Sercarz, F. Celada, N.A. Mitchison and T. Tada (eds.), pp. 257–271, Springer-Verlag, New York.CrossRefGoogle Scholar
  13. Hoffmann, G.W. and F. Tufaro. (1989). Serological distance coefficients. Immunol. Letters, in press.Google Scholar
  14. Hughes, R.A.C. (1974). Protection of rats from experimental allergic encephaphalomyelitis with antiserum to guinea pig spinal cord. Immunology 26, 703–711.Google Scholar
  15. Hsia, S., D.M. Doran, R.K. Shockley, P.C. Galle, C.L. Lutcher, and L.D. Hodge. (1984). Unregulated production of virus and/or sperm specific antibodies as a cause of AIDS. Lancet, June 2.Google Scholar
  16. Imagawa, D.T., M.H. Lee, S.M. Wolinsky, K. Sano, F. Morales, S. Kwok, J.J. Sninsky, P.G. Nishanian, J. Giorgi, J.L. Fahey, J. Dudley, B.R. Visscher and R. Detels. Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. The New England Journal of Medicine. 320, 1458–1462.Google Scholar
  17. Jerne, N.K. (1974). Towards a network theory of the immune system. Ann. Immunol. (Inst. Pasteur) 125C, 373–389.Google Scholar
  18. Kingman, S. (1988). Virus develops even with antibodies absent. New Scientist, 26 May.Google Scholar
  19. Kion, T.A. and G.W. Hoffmann. (1989). MHC-mimicking antibodies in MRL-1pr/1pr mice. Manuscript in preparation.Google Scholar
  20. Kopelman, R.G. and S. Zolla-Pazner. (1988). Association of human immunodeficiency virus infection and autoimmune phenomena. Am. J. Med. 84, 82.CrossRefGoogle Scholar
  21. Martinez A.C., M.A.R. Marcos, A. de la Hera, C. Marquez, J.M. Alonso, M.L. Toribio, and A. Coutinho. (1988). Immunological consequences of HIV infection: advantage of being low responder casts doubts on vaccine development. Lancet, Feb. 27.Google Scholar
  22. Meuer, S.C., J.C. Hogdon, R.E. Hussey, J.F. Protentis, S.F. Schlossman and EX. Rheinherz. (1983). Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J. Exp. Med. 158, 988.CrossRefGoogle Scholar
  23. Nakao, A. and Roboz-Einstein, E. (1965). Chemical and immunochemical studies with a dialyzable encephalitogenic compound from the bovine spinal cord. Ann. N.Y. Acad. Sci. 122, 171.CrossRefGoogle Scholar
  24. Paterson, P.Y. and Harwin, S.M. (1963). Suppression of allergic encephalomyelitis in rats by means of antibrain serum J. Exp. Med., 117, 755.CrossRefGoogle Scholar
  25. Perelson, A.S. (1988). (ed.) Theoretical Immunology, Part 2 Addison-Wesley, Redwood City CA.Google Scholar
  26. Richter, P.H. (1975). A network theory of the immune response. Eur. J. Immunol 5, 350–354.CrossRefGoogle Scholar
  27. Safford, J.W. Jr. and S. Tokuda. (1971). Antibody-mediated suppression of the immune response: effect on the development of immunologic memory. J. Immunol 107, 1213–1225.Google Scholar
  28. Shearer, G.M. (1986a). AIDS: An autoimmune pathologic model for the destruction of a subset of helper T lymphocytes. Mount Sinai J. Med. 53, 609–615.Google Scholar
  29. Shearer, G.M. (1986b). Allogeneic leukocytes as a possible factor in induction of AIDS in homosexual men. N. Engl J. Med. 308, 223–224.Google Scholar
  30. Siliciano, R.F., T.J. Hemesath, J.C. Pratt, R.Z. Dintzis, H.M. Dintzis, O. Acuto, H.S. Shin and E.L. Reinherz (1986). Direct evidence for the existance of nominal antigen binding sites on T cell surface Ti aß heterodimers of MHC restricted T cell clones. Cell 47, 161–171.CrossRefGoogle Scholar
  31. Spouge, J.L. (1986). Increasing stability with complexity in a system composed of unstable subsystems. J. Math. Analysis and Applications 118, 502–518.MathSciNetMATHCrossRefGoogle Scholar
  32. Staerz, U.D., H-G. Rammensee, J.D. Benedetto and M.J. Bevan. (1985). Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J. Immunol 134, 3994–4000.Google Scholar
  33. Stricker, R.B., T.M. McHugh, D.J. Moody, W.J.W. Morrow, D.P. Sütes, M.A. Shuman, and J.A. Levy. (1987). An AIDS-related cytotoxic autoantibody with a specific antigen on stimulated CD4+ T cells. Nature 327, 710–713.CrossRefGoogle Scholar
  34. Tarkowski, A., Holmdahl, R., Rubin, K., Klareskog, L.A., Nilsson, L.A. and Gunnarsson, K. (1986). Clin. exp. Immunol 63, 441–449.Google Scholar
  35. Thomas, D.W. and M.J. Solvay (1986). Direct stimulation of T lymphocytes by antigen-conjugated beads. J. Immunol. 137, 419–421.Google Scholar
  36. Uhr, J.W. and Baumann, J.B. 1961. Antibody formation. I. The suppression of antibody formation by passively administered antibody. J. exp. Med. 120, 987.Google Scholar
  37. Uhr J. W. and G. Möller (1968). Regulatory effect of antibody on the immune response. Adv. Immunol 8, 81–127.CrossRefGoogle Scholar
  38. Vulpé, M. (1959). ‘Allergic’ Encephalomyelitis (M. W. Kies and E.C. Alvcord, Eds.), p. 457.Google Scholar
  39. Thomas, Illinois. Waiden, P., Z. A. Nagy and J. Klein (1986). Major histocompatability complex-restricted and unrestricted activation of helper T cell lines by liposome-bound antigens. J. Mol. Cell. Immunol 2, 191.Google Scholar
  40. Ziegler, J.L. and D.P. Stites. (1986). Hypothesis: AIDS is an autoimmune disease directed at the immune system and triggered by a lymphotropic retrovirus. Clin. Immunol, and Immunopath. 41, 305–313.CrossRefGoogle Scholar
  41. Zon, L.I. and Groopman, J.E. (1988). Hematologic manifestations of the human immune deficiency virus (HIV). Seminars in Hematology 25, 208–218.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Geoffrey W. Hoffmann
    • 1
  • Michael D. Grant
    • 1
  1. 1.Departments of Microbiology and PhysicsUniversity of British ColumbiaVancouverCanada

Personalised recommendations