Skip to main content
SpringerLink
Log in

Mechanisms of Autoimmunity

  • Chapter
Immunotoxicology

Part of the book series: Developments in Hematology and Immunology ((DIHI,volume 16))

Abstract

The immune system is highly specialized in recognizing and responding to foreign elements invading from the outside world while no apparent immune reactions develop towards self-constituents. Originally, it had been proposed that this state of self-tolerance was achieved by deletion of selfreactive clones during ontogeny and autoimmunity resulted from the effect of “forbidden clones” (1). From more recent experimental scrutiny, however, we know that potentially autoreactive lymphocytes do exist in the intact, healthy immune system. Normally, however, these cells are controlled by mechanisms precluding their reactivity or, at least, precluding the development of harmful autoimmunity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Burnet, F.M., 1959, In: The Clonal Selection Theory of Acquired Immunity. Vanderbilt University Press, Nashville, Tennessee.

    Google Scholar 

  2. Fialkow, P.J., Gilchrist, C. & Allison, A.C., 1973, Autoimmunity in chronic graft-versus-host disease. Clini. Exp, Immunol. 13, 479–486.

    CAS  Google Scholar 

  3. Gleichmann, E. & Gleichmann, H., 1976, Diseases caused by reactions of T-lymphocytes to incompatible structures of the major histocompatibility complex: I. Autoimmune hemolytic anemia, Eur. J. Immunol. 6, 899–906.

    Article  Google Scholar 

  4. Elven, E.H. vanr Agterberg, J. Sadal, S., & Gleichmann, Em, 1981, Diseases caused by reaction of T lymphocytes to incompatible structures of the major histocompatibility complex: II. Autoantibodies deposited along the basement membrane of skin and their relationship to immune- complex glomerulonephritis. J. Immunol. 126, 1684–1691.

    PubMed  Google Scholar 

  5. Allison, A.C., Denman, A.M. & Barnes, R.D., 1971, Hypothesis. Cooperating and controlling functions of thymus-derived lymphocytes in relation to autoimmunity. Lancet 2, 135–140.

    Article  PubMed  CAS  Google Scholar 

  6. Rose, N.R., Kong, Y,M,, Okayasu, I., Giraldo, A.A., Beisel, K. & Sundick, R.S., 1981, T-cell regulation in autoimmune thyroiditis. Immunol. Rev. 55, 299–314.

    Article  PubMed  CAS  Google Scholar 

  7. Fournie, G.J., Lambert, P.H. & Miescher, P.A., 1974, Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J. Exp. Med. 140, 1189–1206.

    Article  PubMed  CAS  Google Scholar 

  8. Fernandez, C. Hammerstroem, L., Moeller, G., Primi, D. & Smith, C.J.E., 1979, Immunological tolerance affects only a subpopulation of the antigen-specific B lymphocytes: evidence against clonal deletion as the mechanism of tolerance induction. Immumol. rev. 43, 3–41.

    Article  CAS  Google Scholar 

  9. Gleichmann, E., Pals, S.T., Rolonk, A.G., Radaszkiewicz, T. & Gleichmann, H., 1984, Graft-versus-host reactions: clues to the etiopathology of a broad spectrum of immunological diseases, Immunology Today, 5, in press

    Google Scholar 

  10. Cohen, I.R., Ben-Nun, A., Holoshitz, J., Maron, R. & Zerubavel, R., 1983, Vaccination against autoimmune T lymphocytes. Immunology Today, 4, 227–230.

    Article  Google Scholar 

  11. Hohlfeld, R., Toyka, K.V., Heininger, K., Grosse-Wilde, H. & Kalies, I. 1984, Autoimmune human T-lymphocytes specific for acetylcholine receptor are restricted to HLA-DR and inhibited by anti-DR antibodies. Nature 310, 244–246.

    Article  PubMed  CAS  Google Scholar 

  12. Bona, C. & Paul, W. E., 1979, Cellular basis of regulation of expression of idiotype. I. T-suppressor cells specific for MOPC 460 idiotype regulate the expression of cells secreting anti-TNP bearing 460 idiotype. J. Exp. Med., 149, 592–600.

    Article  PubMed  CAS  Google Scholar 

  13. Koelsch, E., 1984, interaction of suppressor & helper antigenic determinants in the dominance of either tolerance or immunity (editorial). Scand. J. Immunol. 19, 387–393.

    Article  Google Scholar 

  14. Hamilton, H.E., Morgan, D.P. & Simmons, A. (1978), A pesticide (dieldrin)-induced immunohemolytic anemia. Environ. Research, 17, 155–164.

    Article  CAS  Google Scholar 

  15. Ercegovich, C.D., 1973r Relationship of pesticides to immune responses. Fed. Proc. 32, 2010–2016.

    PubMed  CAS  Google Scholar 

  16. Weigle, W.O., 1980, Analysis of autoimmunity through experimental models of thyroiditis and allergic encephalomyelitis. Adv. Immunol. 30, 159–275.

    Article  PubMed  CAS  Google Scholar 

  17. Cox, K.O., & Howies, A., 1981, Induction and regulation of autoimmune hemolytic anemia in mice. Immunol. Rev. 55, 31-51.

    Article  PubMed  CAS  Google Scholar 

  18. Bacigalupo, A., Podesta, M., Van Lint, M.R., Vimercati, R., Cerri, R, Rossi, E., Risso, M., Carella, A., Santim, G., Damasio, E., Giordano, D. and Marmont, A.A., 1981. Severe aplastic anemia: correlation of in vitro tests with clinical response to immunosuppression in 20 patients. Brit. J. Haematol. 47, 423–432.

    Article  CAS  Google Scholar 

  19. Torok-Storb, B.J., Sieff, C., Storb, R., Adamson, J. & Thomas E.D., 1980, In vitro tests for distinguishing possible immune-mediated aplastic anemia from transfusion-induced sensitization. Blood 55, 211–215.

    PubMed  CAS  Google Scholar 

  20. Hansen, J.A., Woodruff, J.M. & Good, R.A., 1981, The graft-versus-host reaction in man. Genetics clinical features and immunopathology. In: Comprehensive Immunology. Safai, B. Good, R.A. (eds.) J New York, Plenum Press 7, 229–257.

    Google Scholar 

  21. Brill, H. & Benner, R.. 1982. Cell-mediated immunity to histocompatibility antigens. CRC Crit. Lab. Sci. (in press)

    Google Scholar 

  22. Beschorner, W.E., P.J. Tutschka & G.W. Santos, 1982. Chronic graft versus-host disease in the rate rediation chimera. Transplantation 33 393–399.

    Article  PubMed  CAS  Google Scholar 

  23. Gleichemann, H. & Wllke, W., 1976, Autoimmunization and lymphomagenesis in parent Fi combinations differing at the major histocompatibility complex: model for spontaneous disease caused by altered self-Antigens? Transplant. Rev. 31, 156–224.

    PubMed  CAS  Google Scholar 

  24. Gleichmann, E., van Elven, E.H., van der Veen, J.P.W., 1982, A systemic lupus erythematosus (SLE)-like disease in mice induced by abnormal T-B-cell cooperation. Preferential formation of autoantibodies characteristic of SLE. Eur. J. Immunmol. 12, 152–158.

    Article  CAS  Google Scholar 

  25. van Rappard-van der Veen, F.M., Kiesel, U, Poels, L. Schuler. W., Melief, C.J.M., Landegent, J. & Gleichmann, E., 1984, Further evidence against random polyclonal antibody formation in mice with lupus-like graft-versus host disease. J. Immunol. 132, 1814–1820.

    Google Scholar 

  26. van Rappard-van der Venn, F.M., Rolihk, A.G., & Gleichmann, E., 1982, Diseases caused by reactions of T lymphocytes towards incompatible structures of the major histocompatibility complex. VI. Autoantibodies characteristic of systemic lupus erythematosus induced by abnormal T-B-cell cooperation across I-E. J. Exp. Med. 155, 1555–1560.

    Article  Google Scholar 

  27. Rolihk, A.G., Pals, S.T. & Gleichmann, E., 1983, Allosuppressor- and allohelper-T cells in acute and chronic graft-versus-host disease. II. F1 recipients carrying mutations at H-2K and/or I-A J. Exp. Med. 157. 755–771.

    Article  PubMed  CAS  Google Scholar 

  28. Rolihk, A.G. & Gleichmann, E., 1983, Allosuppressor and allohelper-T cells in acute and chronic graft-versus-host disease. III. Different Lyt subsets of donor T cells induce different pathological symptoms. J. Exp. Med. 158, 546–558.

    Article  PubMed  CAS  Google Scholar 

  29. Pals, S.T., Radaszkiewicz, T. & Gleichmann, E., 1984, Allosuppressorand allohelper-T cells in acute and chronic graft-versus-host disease. IV. Activation of donor allosuppressor cells is confined to acute GVHD. J. Immunol. 132, 1669–1678.

    PubMed  CAS  Google Scholar 

  30. Rolihk, A.G., Gleichmann, H. & Gleichmann, E., 1983, Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. VII Immune-complex glomerulonephritis. J. Immunol. 130, 209–215.

    PubMed  CAS  Google Scholar 

  31. van Rappard-van der Veen, F.M., Radaszkiewicz, T., Terraneo, L. & Gleichmann, E., 1983, Attempts at standardization of lupus-like graft-versus-host disease: Inadvertent repopulation by DBA/2 spleen cells of H-2-different non-irradiated F1 mice. J. Immunol. 130, 2693–2701.

    Google Scholar 

  32. Pals, S.T., Radaszkiewicz, T., Roozendaal, L. & Gleichmann, E., 1984, Chronic progressive polyarthritis and other symptoms of collagen vascular disease induced by graft-versus-host reaction. J. Immunol., (in press).

    Google Scholar 

  33. Rolink, A.G., Radaszkiewicz, T., Pals, S.T., van der Meer., & Gleichmann, E., 1982, Allosuppressor- and allohelper-T cells in acute and chronic graft-versus-host disease. I. Alloreactive suppressor cells rather than killer T cells appear to be the decisive effector cells in lethal graft-versus-host disease. J. Exp. Med. 155, 1501–1522.

    Article  PubMed  CAS  Google Scholar 

  34. Pals, S.T., Gleichmann, H. & Gleichmann, E., 1984, Allosuppressor- and allohelper-T cells in acute and chronic graft-versus-host disease. V. F1 mice with secondary chronic GVHD contain F1-reactive allohelper but no allosuppressor T cells. J. Exp. Med. 159, 508–523.

    Article  PubMed  CAS  Google Scholar 

  35. Rolirik, A.G., van der Meer, W.G.K., Melief, C.J.M. & Gleichmann, E., 1983, Intra-H-2 requirements for the induction of maximal positive and negative allogeneic effects in vitro. Eur. J. Immunol. 13, 191–197.

    Article  PubMed  CAS  Google Scholar 

  36. Pals, S.T., Zijlstra, M., Radaszkiewicz, T., Cuypers, T., Schoenmakers, H.J., Melief, C.J.M., Berns, A. & Gleichmann, E., 1984, Immunological induction of malignant lymphoma: graft-versus-host reaction-induced- B-cell lymphomas contain reintegrations of several types of murine leukemia virus sequences. (submitted for publication)

    Google Scholar 

  37. Hurtenbach, U. & Shearer, G.M., 1983, Analysis of murine T-lymphocyte markers during the early phases of GVH-associated suppression of cytotoxic T-lymphocytes response. J. Immunol. 13, 1561–1566.

    Google Scholar 

  38. Bretscher, P., 1913, Hypothesis: a model for generalised autoimmunity. Cell Immunol. 6, 1–11.

    Article  PubMed  CAS  Google Scholar 

  39. Katz, D.H., 1977, Lymphocyte differentiation, recognition and regulation. Nez York, Academic Press Inc., 410–482.

    Google Scholar 

  40. Ordal, J.C. & Grumet, F.C., 1972, Genetic control of the immune response.The effect of graft-versus-host reaction on the antibody response to poly-L (Tyr, Glu)-poly-D, L-Ala-poly-L-Lys in nonresponder mice. J. Exp. Med. 136, 1195–1206.

    Article  PubMed  CAS  Google Scholar 

  41. Elfenbein, G.J., Green, I. & Paul, W.E., 1973, The allogeneic effect: increased affinity of serum antibody produced during a secondary response. Eur. J. Immunol. 3, 640–644.

    Article  PubMed  CAS  Google Scholar 

  42. McCullagh, P.J., 1972, The abrogation of immunological tolerance by means of allogeneic confrontation. Transplant. Rev. 12, 180–207.

    PubMed  CAS  Google Scholar 

  43. Feldmann, M. & Basten, A., 1972, Cell interactions in the immune response in vitro. IV. Comparison of the effects of antigen-specific and allogeneic thymus-derived cell-factors. J. Exp. Med. 136, 722–736.

    Article  PubMed  CAS  Google Scholar 

  44. Hamilton, J.A. & Miller, J.F.A.P., 1973, Induction of a primary antihapten response in vivo by a GVHR. J. Exp. Med. 138, 1009–1014.

    Article  PubMed  CAS  Google Scholar 

  45. Klaus, G.G.B. & McMichael, A.J., 1974, Immunological properties of haptens coupled to thymus-independent carrier molecules. II. The influence of the GVHR on primary antibody responses to hapten-coupled polysaccharides and proteins. Eur. J. Immunol. 4, 505–511.

    Article  PubMed  CAS  Google Scholar 

  46. Osborne, D.P. & Katz, D.H., 1973, The allogeneic effect in inbred mice. III. Unique antigenic structural requirements in the expression of the phenomenon on unprimed cell populations in vivo. J. Exp. Med. 137, 991–1008.

    Article  PubMed  CAS  Google Scholar 

  47. Golding, H. & Ritteriberg, M.B., 1982, In vitro and in vivo allogeneic effects: differential modulation of B-cell subpopulations. J. Immunol. 128, 1625–1629.

    PubMed  CAS  Google Scholar 

  48. Golding, H. & Rittenberg, M.B., 1982, In vivo allogeneic effects: shift in the isotype profile of primary TI-2 responses in mice undergoing graft-vs-host reaction. J. Immunol. 129, 1878–1882.

    PubMed  CAS  Google Scholar 

  49. Kindred, B. & Shreffler, B.C., 1972, H-2 dependence of cooperation between T and B cells in vivo. J. Immunol. 109, 940–943.

    PubMed  CAS  Google Scholar 

  50. Benacerraf, B. & Germain, R.N., 1978, The immune res-ponse genes of the major histocompatibility complex. Immunol. Rev. 38, 70–119.

    Article  PubMed  CAS  Google Scholar 

  51. Zihkernagel, R.M. & Doherty, P.C., 1975, H-2 compati-bility requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificaties are associated with structures coded for in H-2K or H-2D. J. Exp. Med. 141, 1427–1436.

    Article  PubMed  CAS  Google Scholar 

  52. Shelby, H.J. Rothman, S.J. & Buckley, R.H., 1980, Phenytoin hypersensitivity. J. Allergy Clin. Immunol. 66, 166–172.

    Article  Google Scholar 

  53. Rosenthal, C.J., Noguera, C.A., Coppola, A. & Kapelner, S.N., 1982, Pseudolymphoma with mycosis fungoides manifestations, hyperresponsiveness to diphenylhydantoin, and lymphocyte disregulation. Cancer 49, 2305–2314.

    Article  PubMed  CAS  Google Scholar 

  54. Jaffe, I.A., 1979, Penicillamine in rheumatoid arthritis: clinical pharmacology and biochemical properties. Scand. J. Rheumatol. (Suppl). 28, 58–64.

    Article  CAS  Google Scholar 

  55. Editorial. Captopril: benefits and risks in severe hypertension. Lancet 2, 129–130.

    Google Scholar 

  56. Batchelor, J.R., Welsh, K.I., Mansilla-Tinoco, R., Dollery, C.T., Hughes, G.R.V., Bernstein, R., Ryan, P., Maish, P.F., Aber, G.M., Blng, R.F. & Russel, G.I., 1980, Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex on susceptibility. Lancet 1, 1107–1109.

    Article  PubMed  CAS  Google Scholar 

  57. Gleichmann, H., 1981, Studies on the mechanism of drug sensitization: T cell-dependent popliteal lymph node reaction to diphenylhydantoin. Clin. Immunopathol. 18, 203–211.

    Article  CAS  Google Scholar 

  58. Gleichmann, H., Pals, S.T. & Radaskiewicz, T., 1983, T cell-dependent B-cell proliferation and activation induced by administration of the drug diphenylhydantoin to mice. Hematol. Oncology 1, 165–176.

    Article  CAS  Google Scholar 

  59. Holland, P. and Mauer, A., 1965, Drug-induced in vitro stimulation of peripheral lymphocytes. Lancet 1, 1368–1369.

    Google Scholar 

  60. Schoepf, E., Schultz, K.H., Kessler, R., Taugner, M. & Braun, W., 1975, Allergologische Untersuchungen beim Lyell-Syndrome. Z. Hautkr. 50, 865–873.

    Google Scholar 

  61. Hyman, L.R., Ballow, M. & Knieser, M.R., 1978, Diphenyl-hydantoin interstitial nephritis: roles of cellular and humoral immunologic injury. J. Pediatr. 92, 915–920.

    Article  PubMed  CAS  Google Scholar 

  62. Druet, P., Sapin, C. Druet, E. & Hirsch, F., 1983, Genetic control of mercury-induced immune response in the rat. In: Nephrotoxic Mechanisms of Drugs and Environmental Toxins. (Ed. G.A. Porter ), Plenum Medical Book Company, New York/London, 425–435.

    Google Scholar 

  63. Weening, J., Hoedemaker, P.J. & Bakker, W.W., 1981, Immunoregulation and anti-nuclear antibodies in mercury-induced glomerulopathy in the rat. 45, 64–71.

    CAS  Google Scholar 

  64. Perry, H.M., 1981, Possible mechanisms of the hydralazine-related lupus-like syndrome. Arthritis Rheum. 24, 1093–1104.

    Article  PubMed  CAS  Google Scholar 

  65. Worlledge, S.M., 1973, Immune drug-induced hemolytic anemias. Sem. Hematol. 10, 327–344.

    CAS  Google Scholar 

  66. Wooley, P.H., Griffen, J., Panayi, G.S., Batchelor, J.R., Welsh, K.I. & Gibson, T.H., 1980, HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. N. Engl. J. Med. 303, 300–302.

    Article  PubMed  CAS  Google Scholar 

  67. Black, C.M., Walker, A.E. & Catoggio, L.J., 1983, Genetic susceptibility to scleroderma-like syndrome induced by vinyl chloride. Lancet 1, 53–55.

    Article  PubMed  CAS  Google Scholar 

  68. Vicario, J.L., Serrano-Rios, M., San Andres, F. & Arnaiz-Villena, A., 1982, HLA-DR3, DR4 increase in chronic stage of Spanish oil disease. Lancet 1, 276.

    Article  PubMed  CAS  Google Scholar 

  69. Shakir, R.A., Behan, P.O., Dick, H. & Lambie, D.G., 1978, Metabolism of immunoglobulin A, Lymphocyte function, and histocompatibility antigens in patients on anticonvulsants. J. Neurol. Neurosurg. Psychiatry. 41, 307–311. IMMUNOGL

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Diabetes-Research Institute and Medical Institute of Environmental Hygien at the University of Duesseldorf, Duesseldorf, Germany

    Helga Gleichmann & Ernst Gleichmann

Authors
  1. Helga Gleichmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ernst Gleichmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Commission of the European Communities, Luxembourg

    A. Berlin (Health and Safety Directorate) (Health and Safety Directorate)

  2. Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA

    J. Dean

  3. International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland

    M. H. Draper  & E. M. B. Smith  & 

  4. Institute of Pharmacological Research “Mario Negri”, Milan, Italy

    F. Spreafico

Rights and permissions

Reprints and permissions

Copyright information

© 1987 ECSC, EEC, EAEC, Brussels-Luxembourg and WHO, Geneva

About this chapter

Cite this chapter

Gleichmann, H., Gleichmann, E. (1987). Mechanisms of Autoimmunity. In: Berlin, A., Dean, J., Draper, M.H., Smith, E.M.B., Spreafico, F. (eds) Immunotoxicology. Developments in Hematology and Immunology, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-4307-0_5

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-4307-0_5

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-8414-7

  • Online ISBN: 978-94-009-4307-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation