Idiopathic Inflammatory Bowel Disease (IBD): A Review of Immunological Mechanisms

  • R. G. Shorter
Part of the Developments in Gastroenterology book series (DIGA, volume 3)


While the etiology and pathogenesis of IBD are unknown, a favored hypothesis includes the participation of (1) external agents, possibly microbial, (2) immunological responses in the host, and (3) genetic factors influencing these responses. The purpose of this review is to summarize the immunological evidence that has led to such speculation.


Inflammatory Bowel Disease Ulcerative Colitis Colonic Epithelial Cell Ative Colitis Suppressor Cell Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Broberger O, Perlmann P. 1962. Demonstration of an epithelial antigen in colon by means of fluorescent antibodies from children with ulcerative colitis. Journal Experimental Medicine, 115:13.CrossRefGoogle Scholar
  2. 2.
    Hammarström S, et al. 1965. Immunological studies in ulcerative colitis: II.“Colon” antigen and human blood group A-and H-like antigens in germfree rats. Journal Experimental Medicine, 122:1075.CrossRefGoogle Scholar
  3. 3.
    Harrison WJ. 1965. Autoantibodies against intestinal and gastric mucous cells in ulcerative colitis. Lancet, 1:1346.CrossRefGoogle Scholar
  4. 4.
    Klavins JV. 1962. Demonstration of antibody in serum of ulcerative colitis which combines with cytoplasm of colonic mucosal cells. Journal American Medical Association, 180: 759.Google Scholar
  5. 5.
    Koffler D, et al. 1962. Immunocytochemical studies in ulcerative colitis and regional ileitis. American Journal Pathology, 41:733.Google Scholar
  6. 6.
    Lagercrantz R, et al. 1966. Immunological studies in ulcerative colitis. III. Incidence of antibodies to colon-antigen in ulcerative colitis and other gastro-intestinal diseases. Clinical Experimental Immunology, 1:263.Google Scholar
  7. 7.
    Wright R, Truelove SC. 1966. Auto-immune reactions in ulcerative colitis. Gut, 7:32.PubMedCrossRefGoogle Scholar
  8. 8.
    Zeromski J, et al. 1970. Immunological studies in ulcerative colitis. VII. Anti-colon antibodies of different immunoglobulin classes. Clinical Experimental Immunology, 7:469.Google Scholar
  9. 9.
    Broberger O, Perlmann P. 1959. Autoantibodies in human ulcerative colitis. Journal Experimental Medicine, 110:657.CrossRefGoogle Scholar
  10. 10.
    Carlsson HE, Lagercrantz R, Perlmann P. 1977. Immunological studies in ulcerative colitis. VIII. Antibodies to colon antigen in patients with ulcerative colitis, Crohn’s disease and other diseases. Scandinavian Journal Gastroenterology, 12:707.CrossRefGoogle Scholar
  11. 11.
    Deodhar SD, Michener WM, Farmer RG. 1969. A study of the immunologic aspects of chronic ulcerative colitis and trans-mural colitis. American Journal Clinical Pathology, 51:591.Google Scholar
  12. 12.
    Eckhardt R, Heinisch M, Meyer zum Büschenfelde KH. 1976. Cellular immune reactions against common antigen, small intestine, and colon antigen in patients with Crohn’s disease, ulcerative colitis, and cirrhosis of the liver. Scandinavian Journal Gastroenterology, 11:49.Google Scholar
  13. 13.
    Thayer WR, et al. 1969. Escherichia coli 0:14 and colon hemagglutinating antibodies in inflammatory bowel disease. Gastroenterology, 57:311.PubMedGoogle Scholar
  14. 14.
    Broberger O, Perlmann P. 1963. In vitro studies of ulcerative colitis. I. Reactions of patients’ serum with human fetal colon cells in tissue cultures. Journal Experimental Medicine, 117:705.CrossRefGoogle Scholar
  15. 15.
    Kemler BJ, Alpert F. 1979. Immunopathogenesis of inflammatory bowel disease: studies of cytotoxicity of isolated human colon epithelial cells. Clinical Research, 27:455.Google Scholar
  16. 16.
    McGiven AR, Datta SP, Nairn RC. 1967. Human serum antibodies against rat colon mucosa. Nature, 214:288.PubMedCrossRefGoogle Scholar
  17. 17.
    Lagercrantz R, et al. 1968. Immunological studies in ulceraative colitis. IV. Origin of autoantibodies. Journal Experimental Medicine, 128:1339.CrossRefGoogle Scholar
  18. 18.
    Perlmann P, et al. 1965. Antigen from colon of germfree rats and antibodies in human ulcerative colitis. Annals New York Academy of Sciences, 124:377.CrossRefGoogle Scholar
  19. 19.
    Triger DR, Alp MH, Wright R. 1972. Bacterial and dietary antibodies in liver disease. Lancet, 1:60.PubMedCrossRefGoogle Scholar
  20. 20.
    Bicks RO, Walker RH. 1962. Immunologic “colitis” in dogs. American Journal Digestive Diseases, 7:574.CrossRefGoogle Scholar
  21. 21.
    Shean FC, Barker WF, Fronkalsrud EW. 1964. Studies on active and passive antibody induced colitis in the dog. American Journal Surgery, 107:337.CrossRefGoogle Scholar
  22. 22.
    Lagercrantz R, Perlmann P, Hammarström S. 1971. Immunological studies in ulcerative colitis. V. Family studies. Gastroenterology, 60:381.PubMedGoogle Scholar
  23. 23.
    Delpre G, et al. 1980. HLA antigens in ulcerative colitis and Crohn’s disease in Israel. Gastroenterology, 78:1452.PubMedGoogle Scholar
  24. 24.
    Burnham WR, Gelsthorpe K, Langman MJS, et al. 1980. HLA-D related antigens in inflammatory bowel disease. Gut, 21:916.CrossRefGoogle Scholar
  25. 25.
    McConnell RB. 1980. Inflammatory bowel disease: newer views of genetic influence. In, Developments in Digestive Diseases. Edited by JE Berk. Philadelphia, Lea & Febiger, p129.Google Scholar
  26. 26.
    Perlmann P, et al. 1967. Autoantibodies to colon in rats and human ulcerative colitis: cross-reactivity with Escherichia coli 0:14 antigen. Proceedings Society Experimental Biology Medicine, 125:975.Google Scholar
  27. 27.
    Kunin CM. 1963. Separation, characterization, and biological significance of a common antigen in Enterobacteriaceae. Journal Experimental Medicine, 118:565.CrossRefGoogle Scholar
  28. 28.
    Hammarström S, et al. 1971. Immunochemistry of the common antigen of Enterobacteriaceae (Kunin): relation to lipopolysaccharide core structure. Journal Experimental Medicine, 134:565.CrossRefGoogle Scholar
  29. 29.
    Bartnik W, Kaluzewski S. 1979. Cellular and humoral responses to the Kunin antigen (CA) in ulcerative colitis and Crohn’s disease. Archivum Immunologiae Therapiae Experimentalis, 27:531.Google Scholar
  30. 30.
    Tabaqchali S, O’Donoughue DP, Bettelheim KA. 1978. Escherichia coli antibodies in patients with inflammatory bowel disease. Gut, 19:108.PubMedCrossRefGoogle Scholar
  31. 31.
    Fiasse R, et al. 1978. Circulating immune complexes and disease activity in Crohn’s disease. Gut, 19:611.PubMedCrossRefGoogle Scholar
  32. 32.
    Hodgson HJF, Potter BJ, Jewell DP. 1977. Immune complexes in ulcerative colitis and Crohn’s disease. Clinical Experimental Immunology, 29:187.Google Scholar
  33. 33.
    Jewell DP, MacLennan ICM. 1973. Circulating immune complexes in inflammatory bowel disease. Clinical Experimental Immunology, 14:219.Google Scholar
  34. 34.
    Kemler BJ, Alpert E. 1980. Inflammatory bowel disease associated circulating immune complexes. Gut, 21:195.PubMedCrossRefGoogle Scholar
  35. 35.
    Soltis RD, et al. 1979. Evidence against the presence of circulating immune complexes in chronic inflammatory bowel disease. Gastroenterology, 76:1380.PubMedGoogle Scholar
  36. 36.
    Mee AS, et al. 1979. Chronic immune colitis in rabbits. Gut, 20:1.PubMedCrossRefGoogle Scholar
  37. 37.
    Beeken WL, Sessions JT, Bozymski EM. 1979. Correlations between clinical, blood leukocyte, and skin test data in the National Cooperative Crohn’s Disease Study. Gastroenterology, 77:921.PubMedGoogle Scholar
  38. 38.
    Brown SM, et al. 1970. Short-term lymphocyte cultures in regional enteritis. Lancet, 1:1112.PubMedCrossRefGoogle Scholar
  39. 39.
    Jones JV, et al. 1969. Development of delayed hypersensitivity to dinitrochlorobenzene in patients with Crohn’s disease. Gut, 10:52.PubMedCrossRefGoogle Scholar
  40. 40.
    Meuwissen SGM, et al. 1975. Impaired anamnestic cellular immune response in patients with Crohn’s disease. Gut, 16: 854.PubMedCrossRefGoogle Scholar
  41. 41.
    Meyers S, et al. 1976. Anergy to dinitrochlorobenzene and depression of T-lymphocytes in Crohn’s disease and ulcerative colitis. Gut, 17:911.PubMedCrossRefGoogle Scholar
  42. 42.
    Parent K, Barrett J, Wilson ID. 1971. Investigation of the pathogenic mechanisms in regional enteritis with in vitro lymphocyte cultures. Gastroenterology, 61:431.PubMedGoogle Scholar
  43. 43.
    Phear DN. 1958. The relationship between regional ileitis and sarcoidosis. Lancet, 2:1250.PubMedCrossRefGoogle Scholar
  44. 44.
    Sachar DB, et al. 1973. Impaired lymphocyte responsiveness in inflammatory bowel disease. Gastroenterology, 64:203, 1973.Google Scholar
  45. 45.
    Sachar DB, et al. 1976. T and B lymphocytes and cutaneous anergy in inflammatory bowel disease. Annals New York Academy Sciences, 278:565.CrossRefGoogle Scholar
  46. 46.
    Walker JG, Greaves MF. 1969. Delayed hypersensitivity and lymphocyte transformation in Crohn’s disease and proctocolitis. Gut, 10:414.PubMedGoogle Scholar
  47. 47.
    Williams WJ. 1965. A study of Crohn’s syndrome using tissue extracts and the Kveim and Mantoux tests. Gut, 6:503.PubMedCrossRefGoogle Scholar
  48. 48.
    Aas J, et al. 1972. Inflammatory bowel disease: lymphocytic responses to nonspecific stimulation in vitro. Scandinavian Journal Gastroenterology, 7:299.CrossRefGoogle Scholar
  49. 49.
    Auer IO, Buschmann C, Ziemer E. 1978. Immune status in Crohn’s disease. 2. Originally unimpaired primary cell mediated immunity in vitro. Gut, 19:618.PubMedCrossRefGoogle Scholar
  50. 50.
    Binder HJ, Spiro HM, Thayer WR. 1966. Delayed hypersensitivity in regional enteritis and ulcerative colitis. American Journal Digestive Diseases, 11:572.CrossRefGoogle Scholar
  51. 51.
    Bird AG, Britton S. 1974. No evidence for decreased lymphocyte reactivity in Crohn’s disease. Gastroenterology, 67: 926.PubMedGoogle Scholar
  52. 52.
    Bolton PM, et al. 1974. The immune competence of patients with inflammatory bowel disease. Gut, 15:213.PubMedCrossRefGoogle Scholar
  53. 53.
    MacPherson BR, Albertini RJ, Becken WI. 1976. Immunological studies in patients with Crohn’s disease. Gut, 17:100.PubMedCrossRefGoogle Scholar
  54. 54.
    Röpke C. 1972. Lymphocyte transformation and delayed hypersensitivity in Crohn’s disease. Scandinavian Journal Gastroenterology, 7:671.CrossRefGoogle Scholar
  55. 55.
    Thayer WR, et al. 1978. Skin test reactivity in inflammatory bowel disease in the United States and Czechoslovakia. American Journal Digestive Diseases, 23:337.CrossRefGoogle Scholar
  56. 56.
    Asquith P, Kraft SC, Rothberg RM. 1973. Lymphocyte responses to nonspecific mitogens in inflammatory bowel disease. Gastroenterology, 65:1.PubMedGoogle Scholar
  57. 57.
    Hintz CF, Perlmann P, Hammarström S. 1967. Reactivity in vitro of lymphocytes from patients with ulcerative colitis. Journal Laboratory Clinical Medicine, 70:752.Google Scholar
  58. 58.
    Hunt PS, Trotter S. 1973. Lymphoblastic response to autologous colon epithelial cells in ulcerative colitis in vitro. Gut, 14:875.PubMedCrossRefGoogle Scholar
  59. 59.
    Meyers S, et al. 1978. Significance of anergy to dinitrochlorobenzene (DNCB) in inflammatory bowel disease: family and postoperative studies. Gut, 19:249.PubMedCrossRefGoogle Scholar
  60. 60.
    Rubinstein A, et al. 1978. Comparative analysis of systemic immunological parameters in ulcerative colitis and idiopathic proctitis: effects of sulfasalazine in vivo and in vitro. Clinical Experimental Immunology, 33:217.Google Scholar
  61. 61.
    Bartnik W, Shorter RG. 1980. Inflammatory bowel disease: immunologic developments. In, Developments in Digestive Diseases. Edited by JE, Berk. Philadelphia, Lea & Febiger, p109.Google Scholar
  62. 62.
    Perlmann P, Broberger O. 1963. In vitro studies of ulcerative colitis. II. Cytotoxic action of white blood cells from patients on human fetal colon cells. Journal Experimental Medicine, 117:717.CrossRefGoogle Scholar
  63. 63.
    Watson DW, Quigley A, Bolt RJ. 1966. Effect of lymphocytes from patients with ulcerative colitis on human adult colonic epithelial cells. Gastroenterology, 51:985.PubMedGoogle Scholar
  64. 64.
    Shorter RG, et al. 1968. Inhibition of in vitro. cytotoxicity of lymphocytes from patients with ulcerative colitis and granulomatous colitis for allogenic colonic epithelial cells using horse anti-human thymus serum. Gastroenterology, 54: 227.PubMedGoogle Scholar
  65. 65.
    Shorter RG, et al. 1969. Further studies of in vitro cytotoxicity of lymphocytes from patients with ulcerative and granulomatous colitis for allogeneic colonic epithelial cells, including the effects of colectomy. Gastroenterology, 56: 304.PubMedGoogle Scholar
  66. 66.
    Kemler BJ, Alpert E. 1980. Inflammatory bowel disease: study of cell-mediated cytotoxicity for isolated human colonic epithelial cells. Gut, 21:353.PubMedCrossRefGoogle Scholar
  67. 67.
    Shorter RG, et al. 1971. Inflammatory bowel disease: cytophilic antibody and the cytotoxicity of lymphocytes for colonic cells in vitro. American Journal Digestive Diseases, 16:673.CrossRefGoogle Scholar
  68. 68.
    Stobo JD, et al. 1976. In vitro studies of inflammatory bowel disease: surface receptors of the mononuclear cell required to lyse allogeneic colonic epithelial cells. Gastroenterology 70:171.PubMedGoogle Scholar
  69. 69.
    Shorter RG, et al. 1969. Further studies of in vitro cytotoxicity of lymphocytes for colonic epithelial cells. Gastroenterology, 57:30.PubMedGoogle Scholar
  70. 70.
    Shorter RG, et al. 1970. Modification of in vitro cytotoxicity of lymphocytes from patients with chronic ulcerative colitis or granulomatous colitis for allogenic colonic epithelial cells. Gastroenterology, 58:692.PubMedGoogle Scholar
  71. 71.
    Shorter RG, Huizenga KA, Spencer RJ. 1972. A working hypothesis for the etiology and pathogenesis of nonspecific inflammatory bowel disease. American Journal Digestive Diseases, 17:1024.CrossRefGoogle Scholar
  72. 72.
    Nagai T, Das KM. 1981. Demonstration of an assay for specific cytolytic antibody in sera from patients with ulcerative colitis. Gastroenterology, 80:1507.PubMedGoogle Scholar
  73. 73.
    Hodgson HJF, Wands JR, Isselbacher KJ. 1978. Decreased suppressor cell activity in inflammatory bowel disease. Clinical Experimental Immunology, 32:451.Google Scholar
  74. 74.
    Ginsburg CH, Masters JT, Falchuk ZM. 1980. Defective autologous mixed-lymphocyte reactions and suppressor T-cell generation in patients with inflammatory bowel disease. Gastroenterology, 78:1173.Google Scholar
  75. 75.
    Fiocchi C, Battisto JR, Farmer RG. 1979. Gut mucosal lymphocytes in inflammatory bowel disease: isolation and preliminary functional characterization. Digestive Diseases and Sciences, 24:705.PubMedCrossRefGoogle Scholar
  76. 76.
    Fiocchi C, Youngman K, Farmer RG. 1981. Immune regulation in human intestinal mucosa: enhanced suppressor cell activity in inflammatory bowel disease. Gastroenterology, 80:1148.Google Scholar
  77. 77.
    Goodacre R, Bienenstock J. 1979. Loss of suppressor cell activity in intestinal lymphocytes from patients with Crohn’s disease. Gut, 20:A910.Google Scholar
  78. 78.
    Elson CO, Graeff AS, James SP, et al. 1981. Covert Suppressor cells in Crohn’s disease. Gastroenterology, 80:1513.PubMedGoogle Scholar
  79. 79.
    Bull DM, Bookman MA. 1977. Isolation and functional characterization of human intestinal mucosal lymphoid cells. Journal Clinical Investigation, 59:966.CrossRefGoogle Scholar
  80. 80.
    Bartnik W, et al. 1980. Isolation and characterization of colonic intraepithelial and lamina proprial lymphocytes. Gastroenterology, 78:976.PubMedGoogle Scholar
  81. 81.
    Chiba M, et al. 1979. K-cell activity in lamina proprial lymphocytes from the human colon. Digestive Diseases and Sciences, 24:817.PubMedCrossRefGoogle Scholar
  82. 82.
    Goodacre R, et al. 1979. Morphologic and functional characteristics of human intestinal lymphoid cells isolated by a mechanical technique. Gastroenterology, 76:300.PubMedGoogle Scholar
  83. 83.
    Clancy R, Pucci A. 1978. Absence of K cells in human gut mucosa. Gut, 19:273.PubMedCrossRefGoogle Scholar
  84. 84.
    MacDermott RP, et al. 1980. Human intestinal mononuclear cells. I. Investigation of antibody-dependent, lectin-induced and spontaneous cell-mediated cytotoxic capabilities. Gastroenterology, 78:47.PubMedGoogle Scholar
  85. 85.
    Chiba M, Bartnik W, ReMine SG, Thayer WR, Shorter RG. 1981. Human colonic intraepithelial and lamina proprial lymphocytes: cytotoxicity in vitro and the potential effects of the isolation method on their functional properties. Gut, 22:177.PubMedCrossRefGoogle Scholar
  86. 86.
    Segal AW, Loewi G. 1976. Neutrophil dysfunction in Crohn’s disease. Lancet, 2:219.PubMedCrossRefGoogle Scholar
  87. 87.
    Ward M. 1977. The pathogenesis of Crohn’s disease. Lancet, 2:903.PubMedCrossRefGoogle Scholar
  88. 88.
    Rhodes JM, Jewell DP. 1979. White cell chemotaxis in Crohn’s disease and ulcerative colitis. Gut, 20:436.Google Scholar
  89. 89.
    Glass RE, Baker WNW. 1976. Role of the granuloma in recurrent Crohn’s disease. Gut, 17:75.PubMedCrossRefGoogle Scholar
  90. 90.
    Chambers TJ, Morson BC. 1979. The granuloma in Crohn’s disease. Gut, 20:269.PubMedCrossRefGoogle Scholar

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© Martinus Nijhoff Publishers, The Hague 1982

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  • R. G. Shorter

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