Semin Liver Dis 2002; 22(4): 387-394
DOI: 10.1055/s-2002-35708
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Mechanisms of Autoimmunity

Noel R. Rose
  • Department of Pathology and W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Further Information

Publication History

Publication Date:
25 November 2002 (online)

ABSTRACT

The immune system is capable of recognizing any molecule that enters the body through a parenteral route. For that purpose, the lymphocyte population generates a large, diverse repertoire of receptors. Inevitably, many of these receptors recognize endogenous host antigens as well as exogenous molecules. Thus, self-reactive B cells and T cells are present in normal individuals and are potentially capable of producing an autoimmune response. The host consequently depends on certain mechanisms to avoid the harmful effects of autoimmunity. These mechanisms include negative selection in the thymus and bone marrow to delete the higher-affinity T and B cells and peripheral regulatory mechanisms, such as anergy, ignorance, and suppression. Despite such protective mechanisms, autoimmune diseases, collectively, are common in industrialized societies, even though individually most autoimmune diseases are rare. The diseases present differently depending on the site of pathology but share many fundamental mechanisms.

REFERENCES

  • 1 Nossal G JV. A purgative mastery.  Nature . 2001;  412 685-686
  • 2 Delves P J, Roitt I M. The immune system.  N Engl J Med . 2000;  343 37-49
  • 3 Rose N R. Lymphocytes. In: Fink G, ed. Encyclopedia of Stress, vol. 2 San Diego, CA: Academic Press 2000: 641-645
  • 4 Goldrath A W, Bevan M J. Selecting and maintaining a diverse T-cell repertoire.  Nature . 1999;  402 255-262
  • 5 Marchalonis J J, Schluter S F, Edmundson A B. The T-cell receptor as immunoglobulin: paradigm regained.  Proc Soc Exp Biol Med . 1997;  216 303-318
  • 6 Janeway Jr A C. How the immune system works to protect the host from infection: a personal view.  Proc Natl Acad Sci USA . 2001;  98 7461-7468
  • 7 Klein J, Sato A. The HLA system.  N Engl J Med . 2000;  343 702-709
  • 8 Whittingham S, Mackay I R. The ``pemphigus'' antibody and immunopathies affecting the thymus.  Br J Dermatol . 1971;  84 1-6
  • 9 Cohen I. Kadishman's tree, Escher's angels, and the immunological homunculus. In: Coutinho A, Kazatchkine MD, eds. Autoimmunity: Physiology and Disease New York: Wiley-Liss 1994: 7-17
  • 10 Egwuagu C E, Charukamnoetkanok P, Gery I. Thymic expression of autoantigens correlates with resistance to autoimmune disease.  J Immunol . 1997;  159 3109-3112
  • 11 Kappler J W, Staerz U, White J, Marrack P C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex.  Nature . 1988;  332 35-40
  • 12 Fagarasan S, Honjo T. T-independent immune response: new aspects of B cell biology.  Science . 2000;  290 89-92
  • 13 Jones L A, Chin L T, Longo D L, Kruisbeek A M. Peripheral clonal elimination of functional T cells.  Science . 1990;  250 1726-1729
  • 14 Kamradt T, Mitchison N A. Tolerance and autoimmunity.  N Engl J Med . 2001;  344 6550-664
  • 15 Zinkernagel R M, Cooper S, Chambers J. Virus-induced autoantibody response to a transgenic viral antigen.  Nature . 1990;  345 68-71
  • 16 Seddon B, Mason D. The third function of the thymus.  Immunol Today . 2000;  21 95-99
  • 17 Sakaguchi S. Policing the regulators.  Nature Immunol . 2001;  2 283-284
  • 18 Shevach E M. Regulatory T cells in autoimmunity.  Ann Rev Immunol . 2000;  18 423-449
  • 19 Rose N R. Fundamental concepts of autoimmunity and autoimmune disease. In: Krawitt EL, Wiesner R, Nishioka M, eds. Autoimmune Liver Diseases, 2nd ed Amsterdam: Elsevier Science 1998: 1-20
  • 20 Mackay I R. Tolerance and autoimmunity.  BMJ . 2000;  321 93-96
  • 20a Vladutiu A O, Rose N R. Autoimmune murine thyroiditis.  Relation to histocompatibility (H-2) type. Science . 1971;  174 1137-1139
  • 20b Silverman D A, Rose N R. Neonatal thymectomy increases the incidence of spontaneous and methylcholanthrene-enhanced thyroiditis in rats.  Science . 1974;  184 162-163
  • 20c Bacon L D, Kite Jr H J, Rose N R. Relation between the major histocompatibility (B) locus and autoimmune thyroiditis in obese chickens.  Science . 1974;  186 274-275
  • 21 Tomer Y. Unraveling the genetic susceptibility to autoimmune thyroid diseases: CTLA-4 takes the stage.  Thyroid . 2001;  11 167-169
  • 22 Davidson A, Diamond B. Autoimmune diseases.  N Engl J Med . 2001;  345 340-350
  • 23 Brix T H, Kyvik K O, Christensen K, Hegedüs L. Evidence for a major role of heredity in Graves' disease: a population-based study of two Danish twin cohorts.  J Clin Endocrinol Metab . 2001;  86 930-934
  • 24 Rose N R. The role of infection in the pathogenesis of autoimmune disease.  Semin Immunol . 1998;  10 5-13
  • 25 Rose N R, Mackay I R. Molecular mimicry: a critical look at exemplary instances in human diseases.  Cell Mol Life Sci . 2000;  57 542-551
  • 26 Wucherpfennig K W. Mechanisms for the induction of autoimmunity by infectious agents.  J Clin Invest . 2001;  108 1097-1104
  • 27 Mitchell T C, Hildeman D, Kedl R M. Immunological adjuvants promote activated T cell survival via induction of Bcl-3.  Nature Immunol . 2001;  2 397-402
  • 28 Bernal A, Proft T, Fraser J D, Posnett D N. Superantigens in human disease.  J Clin Immunol . 1999;  19 149-157
  • 29 Rose N R, Rasooly L, Saboori A M, Burek C L. Linking iodine with autoimmune thyroiditis.  Environ Health Perspect . 1999;  107(Suppl 5) 749-752
  • 30 Rose N R, Bonita R, Burek C L. Iodine: an environmental trigger of thyroiditis.  Autoimmunity Review . 2002;  1 97-103
  • 31 Goter Robinson J C, White H J, Rose N R. Murine strain differences in response to mercuric chloride: antinucleolar antibodies production does not correlate with renal immune complex deposition.  Clin Immunol Immunopathol . 1997;  83 127-138
  • 32 Rao T, Richardson B. Environmentally induced autoimmune diseases: potential mechanisms.  Environ Health Perspect . 1999;  107(Suppl 5) 737-742
  • 33 Steinman R M, Nussenzweig M C. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance.  Proc Natl Acad Sci USA . 2002;  99 351-358
  • 34 Rose N R. Insights into mechanisms of autoimmune disease based on clinical findings. In: Paul S, ed. Contemporary Immunology: Autoimmune Reactions Totowa, NJ: Humana Press 1998: 5-17
  • 35 Pinkoski M J, Green D R. Murder by proxy.  Nature Immunol . 2000;  1 461-462
  • 36 Rose N R. Autoimmune diseases: tracing the shared threads.  Hosp Pract . 1997;  32 147-154
  • 37 Jacobson D L, Gange S J, Rose N R, Graham N MH. Epidemiology and estimated population burden of selected autoimmune diseases in the United States.  Clin Immunol Immunopathol . 1997;  84 223-243
  • 38 McDonagh J E, Isenberg D A. Development of additional autoimmune diseases in a population of patients with systemic lupus erythematosus.  Ann Rheum Dis . 2000;  59 230-232
  • 39 Tan E M. Autoantibodies in diagnosis and in identifying autoantigens.  The Immunologist . 1999;  July 85-92
  • 40 Nithiyananthan R, Heward J M, Allhabadia A, Franklyn J A, Gough S CL. Polymorphism of the CTLA-4 gene is associated with autoimmune hypothyroidism in the United Kingdom.  Thyroid . 2002;  12 3-6
  • 41 Siegel R M, Chan FK-M, Chun H J, Lenardo M J. The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity.  Nature Immunol . 2000;  1 469-474
  • 42 Burek C L, Hoffman W H, Rose N R. The presence of thyroid autoantibodies in children and adolescents with autoimmune thyroid disease and in their siblings and parents.  Clin Immunol Immunopathol . 1982;  25 395-404
  • 43 Sela M. Specific vaccines against autoimmune diseases.  C R Acad Sci Paris . 1999;  322 933-939
  • 44 Sercarz E E. Driver clones and determinant spreading.  J Autoimmun . 2000;  14 275-277
  • 45 Steinman L. Despite epitope spreading in the pathogenesis of autoimmune disease, highly restricted approaches to immune therapy may still succeed [with a hedge on this bet].  J Autoimmun . 2000;  14 278-282
  • 46 Lernmark Å. Autoimmune diseases: are markers ready for prediction?.  J Clin Invest . 2001;  108 1091-1096
  • 47 Rose N R. Autoimmunity at the turning point: from investigation to intervention.  Autoimmunity Review . 2002;  1 3-4
    >