The lymphoid system and immunologic defense of the digestive tract

  • Jacques Pappo
  • Robert L. Owen
Part of the Electron Microscopy in Biology and Medicine book series (EMBM, volume 4)


Lymphocytes and macrophages are distributed in the intestinal tract as isolated cell populations in the intestinal epithelium and lamina propria and are present in focal aggregates forming lymphoid follicles. Ultrastructural investigation has played a major role in understanding the cellular interactions and cytoarchitectural details critical to function of the mucosal immune system (1–3). The lymphoid tissue of the intestinal tract, which includes that tissue present in the oral cavity, pharynx, Peyer’s patches, appendix, and isolated follicles in the small and large intestines, represents a substantial fraction of the lymphoid elements which make up the immune system. Collectively, these immunologic structures, termed gut-associated lymphoid tissues (GALT), present a large surface area to a variety of potential antigens and respond in a highly coordinated fashion during the recognition of foreign molecules and pathogens. The distribution of lymphoid cells reflects varying antigen load in different regions of the intestine. Lymphoid tissue is prominent in the oropharynx, minimal in the esophagus and stomach, where rapid transit time and acid secretions reduce the antigenic burden, and becomes abundant again in the distal small intestine and the large intestine, where stasis promotes bacterial proliferation.


Germinal Center Lymphoid Follicle Mucosal Immune System Recurrent Tonsillitis Lymphoid Nodule 
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.
    Oláh I, Röhlich P, Törö I: Ultrastructure of Lymphoid Organs — An Electron Microscopic Atlas. Philadelphia and Toronto: JB Lippincott, Budapest: Akademiai Kiado, 1975.Google Scholar
  2. 2.
    Owen RL, Nemanic P: Antigen processing structures of the mammalian intestinal tract: An SEM study of lymphoepithelial organs. Scan Electron Microsc II: 367–378, 1978.Google Scholar
  3. 3.
    Owen RL, Bhalla DK: Lympho-epithelial organs and lymph nodes. In: Biomedical Research Applications of Scanning Electron Microscopy Vol 3, GM Hodges, KE Carr, (eds), London: Academic Press, p 79–169, 1983.Google Scholar
  4. 4.
    Emmings FG, Evans RT, Genco RJ: Antibody response in the parotid fluid and serum of Irus monkeys (Macaca fascicularis) after local immunization with Streptococcus mutans. Infect Immun 12: 281–292, 1975.PubMedGoogle Scholar
  5. 5.
    Nair PNR, Schroeder HE: Local immune response to repeated topical antigen application in the simian labial mucosa. Infect Immun 41: 399–409, 1983.PubMedGoogle Scholar
  6. 6.
    Schroeder HE, Dorig-Schwarzenbach A: Structure and composition of the oral mucous membrane on the lips and cheeks of the monkey, Macaca fascicularis. Cell Tissue Res 224: 89–104, 1982.PubMedCrossRefGoogle Scholar
  7. 7.
    Nair PNR, Schroedr HE: Retrograde access of antigens to the minor salivary glands in the monkey Macaca fascicularis. Arch Oral Biol 28: 145–152, 1983.PubMedCrossRefGoogle Scholar
  8. 8.
    Coleman R, Hand AR: Endocytosis of native and cationized ferritin by rat parotid duct cells. J Dent Res (special issue) 64: 223 (abstract), 1985.Google Scholar
  9. 9.
    Pappo J, Ebersole JL, Taubman MA: Immunol, in press. Resident salivary gland macrophages function as accessory cells in antigen dependent T cell proliferation. Immunol, in press.Google Scholar
  10. 10.
    Oláh I: Structure of the tonsils. In: Tonsils - Structure, Immunology and Biochemistry, F Antoni, M Straub, (eds), Budapest: Akademiai Kiado, p 5–49, 1978.Google Scholar
  11. 11.
    Howie AJ: Scanning and transmission electron microscopy on the epithelium of human palatine tonsils. J Pathol 130: 91–98, 1980.PubMedCrossRefGoogle Scholar
  12. 12.
    Anderson JC: The response of the tonsil and associated lymph nodes of gnotobiotic piglets to the presence of bacterial antigen in the oral cavity. J Anat 117: 191–198, 1974.PubMedGoogle Scholar
  13. 13.
    Watanabe T, Yoshizaki K, Yagura T, Yamamura Y: In vitro antibody formation by human tonsil lymphocytes. J Immunol 113: 608–616, 1974.PubMedGoogle Scholar
  14. 14.
    Hoffman MK, Schmidt D, Oettgen HF: Production of antibody to sheep red cells by human tonsil cells in vitro. Nature 243: 408–410, 1973.PubMedCrossRefGoogle Scholar
  15. 15.
    Geboes K, De Woolf-Peeters C, Rutgeerts P, Janssens J, Vantrappen G, Desmet V: Lymphocytes and Langerhans cells in the human oesophageal epithelium. Virchows Arch [A] 401: 45–55, 1983.CrossRefGoogle Scholar
  16. 16.
    Tabata K, Ohtsuki H, Okabe S: Role of lymphoid nodules in pathogenesis of indomethacin-induced gastric lesions in dogs. Dig Dis Sci 29: 346–352, 1984.PubMedCrossRefGoogle Scholar
  17. 17.
    Carlson JR, Owen RL: Structure and functional role of Peyer’s patches. In: Immunopathology of the Small Intestine, MN Marsh, (ed), Chichester: John Wiley and Sons Ltd, p 21–40, 1986.Google Scholar
  18. 18.
    Abe K, Ito T: A qualitative and quantitative morphologic study of Peyer’s patches of the mouse. Arch Histol Jpn 40: 407–420, 1977.Google Scholar
  19. 19.
    Comes JS: Number, size and distribution of Peyer’s patches in the human small intestine. I. The development of Peyer’s patches. Gut 6: 225–229, 1965.CrossRefGoogle Scholar
  20. 20.
    Mayrhofer G, Pugh CW, Barclay AN: The distribution, ontogeny and origin in the rat of Ia positive cells with dendritic morphology and of Ia antigen in epithelia, with special reference to the intestine. Eur J Immunol 13: 112–122, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Pollard M, Sharon N: Response of the Peyer’s patches in germ-free mice to antigenic stimulation. Infect Immun 2: 96–100, 1970.PubMedGoogle Scholar
  22. 22.
    Ermak TH, Owen RL: Differential distribution of lymphocytes and accessory cells in mouse Peyer’s patches. Anat Rec 215: 144–152, 1986.PubMedCrossRefGoogle Scholar
  23. 23.
    Spencer J, Finn T, Isaacson PG: Human Peyer’s patches: An immunohistochemical study. Gut 27: 405–410, 1986.PubMedCrossRefGoogle Scholar
  24. 24.
    Weisz-Carrington P, Roux ME, McWilliams M, PhillipsQuagliata JM, Lamm ME: Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: Evidence for a generalized secretory immune system. J Immunol 123: 1705–1708, 1979.PubMedGoogle Scholar
  25. 25.
    Bockman DE: Functional histology of appendix. Arch Histol Jpn 46: 271–292, 1983.PubMedCrossRefGoogle Scholar
  26. 26.
    Gorgollón P: The normal human appendix: A light and electron microscopic study. J Anat 126: 87–101, 1978.PubMedGoogle Scholar
  27. 27.
    Ogawa K, Miyoshi M: Intercellular spaces in the lymph nodule _associated epithelium of the rabbit Pever’s patch and appendix. Arch Histol Jpn 48: 53–67, 1985.PubMedCrossRefGoogle Scholar
  28. 28.
    Heatley RV, Bienenstock J: Luminal lymphoid cells in the rabbit intestine. Gastroenterology 82: 268–275, 1982.PubMedGoogle Scholar
  29. 29.
    Bockman DE, Cooper MD: Early lymphoepithelial relationships in human appendix: A combined light and electron microscopic study. Gastroenterology 68: 11601168, 1975.Google Scholar
  30. 30.
    Bockman DE, Boydston WR: Participation of follicle associated epithelium (FAE), macrophages, and plasma cells in the function of the appendix. Scan Electron Microsc III: 1341–1350, 1982.Google Scholar
  31. 31.
    Laufer I, deSa D: Lymphoid follicular pattern: A normal feature of the pediatric colon. Am J Roentgenol 130: 51–55, 1978.Google Scholar
  32. 32.
    Bland PW, Britton DC: Morphological study of antigen-sampling structures in the rat large intestine. Infect Immun 43: 693–699, 1984.PubMedGoogle Scholar
  33. 33.
    O’Leary AD, Sweeney EC: Lymphoglandular complexes of the colon: Structure and distribution. Histopathol 10: 267–283, 1986.CrossRefGoogle Scholar
  34. 34.
    Warshaw AL, Walker WA, Cornell R, Isselbacher KJ: Small intestinal permeability to macromolecules: Transmission of horseradish peroxidase into mesenteric lymph and portal blood. Lab Invest 25: 675–684, 1971.PubMedGoogle Scholar
  35. 35.
    Rhodes RS, Karnovsky MJ: Loss of macromolecular barrier function associated with surgical trauma to the intestine. Lab Invest 25: 220–229, 1971.PubMedGoogle Scholar
  36. 36.
    Peterson JW, Verwey WF: Radiolabeled toxin for studying binding of cholera toxin and toxoids to intestinal mucosal receptor sites. Proc Soc Exp Med Riol 145: 1187–1191, 1974.Google Scholar
  37. 37.
    Waksman BH, Ozer H: Specialized amplification elements in the immune system: The role of nodular lymphoid organs in the mucous membranes. Prog Allergy 21: 1–113, 1976.PubMedCrossRefGoogle Scholar
  38. 38.
    Wolf JL, Bye WA: The membranous epithelial (M) cell and the mucosal immune system. Anna Rev Med 35: 95–112, 1984.CrossRefGoogle Scholar
  39. 39.
    Bhalla DK, Owen RL: Cell renewal and migration in lymphoid follicles of Peyer’s patches and cecum - an autoradiographic study in mice. Gastroenterology 82: 232–242, 1982.PubMedGoogle Scholar
  40. 40.
    Bye WA, Allan CH, Trier JS: Structure, distribution and origin of M Cells in Peyer’s patches of mouse ileum. Gastroenterology 86: 789–801, 1984.PubMedGoogle Scholar
  41. 41.
    Owen RL, Jones AL: Epithelial cell specialization within human Peyer’s patches: An ultrastructural study of intestinal lymphoid follicles. Gastroenterology 66: 189–203, 1974.PubMedGoogle Scholar
  42. 42.
    Smith MW, Peacock MA: M cell distribution in follicle associated epithelium of mouse Peyer’s patches. Am J Anat 519: 167–175, 1980.CrossRefGoogle Scholar
  43. 43.
    Keljo DJ, Hamilton JR: Quantitative determination of macromolecular transport rate across intestinal Peyer’s patches. Am J Physiol 244: 637–644, 1983.Google Scholar
  44. 44.
    Owen RL, Apple RT, Bhalla DK: Morphometric and cytochemical analysis of lysosomes in rat Peyer’s patch follicle epithelium: Their reduction in volume fraction and acid phosphatase content in M cells compared to adjacent enterocytes. Anat Rec 216: 521–527, 1986.PubMedCrossRefGoogle Scholar
  45. 45.
    Owen RL: Sequential uptake of horseradish peroxidase by lymphoid follicle epithelium of Peyer’s patches in the normal unobstructed mouse intestine: An ultrastructural study. Gastroenterology 72: 440–451, 1977.PubMedGoogle Scholar
  46. 46.
    Neutra MR, Hall TL, Mayer EL, Fishkind DJ: Transport of membrane-bound macromolecules by M cells in follicle-associated epithelium of rabbit Peyer’s patch. Cell Tissue Res, 247: 537–546, 1987.PubMedCrossRefGoogle Scholar
  47. 47.
    Wolf JL, Rubin DH, Finberg R, Kauffman RS, Sharpe AH, Trier JS, Fields BN: Intestinal M Cells: A pathway for entry of reovirus into the host. Science 212: 471–472, 1981.PubMedCrossRefGoogle Scholar
  48. 48.
    Owen RL, Pierce NF, Apple RT, Cray WC: M cell transport of Vibrio cholerae from the intestinal lumen into Peyer’s patches: A mechanism for antigen sampling and for microbial transepithelial migration. J Infect Dis 153: 1108–1118, 1986.PubMedCrossRefGoogle Scholar
  49. 49.
    Marcial MA, Madara JL: Cryptosporidium: Cellular localization, structural analysis of absorptive cell-parasite membrane-membrane interactions in guinea pigs, and suggestion of protozoan transport by M cells. Castro-enterology 90: 583–594, 1986.Google Scholar
  50. 50.
    Owen RL, Bhalla DK: Cytochemical analysis of alkaline phosphatase and esterase activities and of lectin-binding and anionic sites in rat and mouse Peyer’s patch M cells. Am J Anat 168: 199–212, 1983.PubMedCrossRefGoogle Scholar
  51. 51.
    Rosner AJ, Keren DF: Demonstration of M cells in the specialized follicle-associated epithelium overlying isolated lymphoid follicles in the gut. J Leukocyte Biol 35: 397–404, 1984.PubMedGoogle Scholar
  52. 52.
    Pappo J: Macrophages of the secretory immunologic system: Identification and functional interactions with T lymphocytes. Doctor of Medical Sciences Thesis, Harvard University, Cambridge, Massachusetts, 1984.Google Scholar
  53. 53.
    Sobhon P: The light and electron microscopic studies of Peyer’s patches in non germ-free adult mice. J Morphol 135: 457–482, 1971.PubMedCrossRefGoogle Scholar
  54. 54.
    Joel DD, Laissue JA, LeFevre ME: Distribution and fate of ingested carbon particles in mice. J Reticuloendothel Soc 24: 477–487, 1978.PubMedGoogle Scholar
  55. 55.
    Owen RL, Allen CL, Stevens DP: Phagocytosis of Giardia muris by macrophages in Peyer’s patch epithelium in mice. Infect Immun 33: 591–601, 1981.PubMedGoogle Scholar
  56. 56.
    Vecchi M, Berti E, Primignani M, Monti M, Agape D, Torgano G, Arosio E, de Franchis R: In situ identification of immune competent cells in gastrointestinal mucosa: An evaluation by immunoelectronmicroscopy. Virchows Archie [A] 406: 407–415, 1985.CrossRefGoogle Scholar
  57. 57.
    Crabbe PA, Carbonara AO, Heremans JF: The normal human intestinal mucosa as a major source of plasma cells containing gamma A-immunoglobulin. Lab Invest 14: 235–248, 1965.PubMedGoogle Scholar
  58. 58.
    Carlson JR, Heyworth MF, Owen RL: Response of Peyer’s patch lymphocyte subsets to Giardia muris infection in BALB/c mice. II. B-cell subsets. Enteric antigen exposure is associated with immunoglobulin switching by Peyer’s patch B cells. Cell Immunol 97: 51–58, 1986.PubMedCrossRefGoogle Scholar
  59. 59.
    Mestecky J, McGhee JR, Arnold RR, Michalek SM, Prince SM, Babb JC: Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. J Clin Invest 61: 731–737, 1978.PubMedCrossRefGoogle Scholar
  60. 60.
    Richman LK, Graeff AS, Yarchoan R, Strober W: Simultaneous induction of antigen-specific IgA helper T cells and IgG suppressor T cells in the murine Peyer’s patch after protein feeding. J Immunol 126: 2079–2083, 1981.PubMedGoogle Scholar
  61. 61.
    Kawanishi H, Saltzman LE, Strober W: Mechanisms regulating IgA-class specific immunoglobulin production in murine gut-associated lymphoid tissue. I. T cells derived from Peyer’s patches that switch sIgM B cells to sIgA B cells in vitro. J Exp Med 157: 433–450, 1983.PubMedCrossRefGoogle Scholar
  62. 62.
    Mattingly JA, Waksman BH: Immunologic suppression after oral administration of antigen. I. Specific suppressor cells formed in rat Peyer’s patches after oral administration of sheep erythrocytes and their systemic migration. J Immunol 121: 1878–1883, 1978.PubMedGoogle Scholar
  63. 63.
    Williams R, Gibbons R: Inhibition of bacterial adherence by secretory immunoglobulin A: A mechanism of antigen disposal. Science 177: 697–699, 1972.PubMedCrossRefGoogle Scholar
  64. 64.
    Taubman MA, Smith DJ: Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats. Infect Immun 9: 1079–1091, 1974.Google Scholar
  65. 65.
    Lowell GH, Smith LF, Artenstein MS, Nash GS, MacDermott RP Jr: Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K lymphocytes and moncytes are effective against meningococci in cooperation with human immune sera. J Exp Med 150: 127–137, 1979.PubMedCrossRefGoogle Scholar
  66. 66.
    Tagliabue A, Nencioni L, Villa L, Keren DF, Lowell GH, Boraschi D: Antibody-dependent cell-mediated antibacterial activity of intestinal lymphocytes with secretory IgA. Nature 306: 184–186, 1983.PubMedCrossRefGoogle Scholar
  67. 67.
    Robinson JO: Congenital absence of vermiform appendix. Br J Surg 39: 344–345, 1952.PubMedCrossRefGoogle Scholar
  68. 68.
    Ogra PL: Effect of tonsillectomy and adenoidectomy on nasopharyngeal antibody response to poliovirus. N Engl J Med 284: 59–64, 1971.PubMedCrossRefGoogle Scholar
  69. 69.
    Surján L Jr: Reduced lymphocyte activation in repeatedly inflamed human tonsils. Acta Otolaryngol (Stockh) 89: 187–194, 1980.PubMedCrossRefGoogle Scholar
  70. 70.
    Maeda S, Mogi G: Functional morphology of tonsillar crypts in recurrent tonsillitis. Acta Otolaryngol (Stockh) (suppl) 416: 7–19, 1984.Google Scholar
  71. 71.
    Karchev T, Kabakchiev P: Electron microscope observations on the tonsillar epithelium in children with recurrent tonsillitis. Int J Pediatr Otorhinolaryngol 4: 149–156, 1982.PubMedCrossRefGoogle Scholar
  72. 72.
    Stewart THM, Hetenyi C, Rowsell H, Orizaga M: Ulcerative enterocolitis in dogs induced by drugs. J Pathol 131: 363–378, 1980.PubMedCrossRefGoogle Scholar
  73. 73.
    Fujimura Y: Functional morphology of microfold cells (M cells) in Peyer’s patches - phagocytosis and transport of BCG by M cells into rabbit Peyer’s patches. Gastroenterol Jpn 21: 325–335, 1986.PubMedGoogle Scholar
  74. 74.
    Rickert RR, Carter HW: The “early” lesion of Crohn’s disease: Correlative light and scanning electron microscopic studies. J Clin Gastroenterol 2: 11–19, 1980.PubMedCrossRefGoogle Scholar
  75. 75.
    Carter PB, Collins FM: The route of enteric infection in normal mice. J Exp Med 139: 1189–1203, 1974.PubMedCrossRefGoogle Scholar
  76. 76.
    Bitar R, G Tarpley J: Intestinal perforation in typhoid fever: A historical and state-of-the-art review. Rev Infect Dis 7: 257–271, 1985.PubMedCrossRefGoogle Scholar
  77. 77.
    Johnson JA, Prescott JF, Markham JF: The pathology of experimental Corynebacterium equi infection in foals following intragastric challenge. Vet Pathol 20: 450–459, 1983.PubMedCrossRefGoogle Scholar
  78. 78.
    Mann RB, Jaffe ES, Braylan RC, Nanba K, Frank MM, Ziegler JL, Berard CW: Nonendemic Burkitt’s lymphoma: A B-cell tumor related to germinal centers. N Engl J Med 295: 685–691, 1976.PubMedCrossRefGoogle Scholar
  79. 79.
    Bost KL, Cuchens MA: The role of the Peyer’s patch in carcinogenesis. I. The adsorption from the gut and retention of 3-methylcholanthrene by Peyer’s patches. Carcinogenesis 7: 1251–1256, 1986.PubMedCrossRefGoogle Scholar
  80. 80.
    Bost KL, Garrett LR, Cuchens MA: The role of the Peyer’s patch in carcinogenesis. II. 3-methylcholanthreneinduced lymphoid malignancies in rat Peyer’s patches. Carcinogenesis 7: 1257–1265, 1986.PubMedCrossRefGoogle Scholar
  81. 81.
    Oohara T, Ogino A, Tohma H: Microscopic adenoma in nonpolyposis coli: Incidence and relation to basal cells and lymphoid follicles. Dis Colon Rectum 24: 120–126, 1981.PubMedCrossRefGoogle Scholar
  82. 82.
    Fujikura S: A study of Peyer’s patch of the terminal ileum. Part 1: A study of the mucosal surface appearance and histological finding in endoscopic cases and autoptic cases. Gastroenterol Endosc (Japan) 26: 1246–1261, 1984.Google Scholar
  83. 83.
    Fujikura S: A study of Peyer’s patch of the terminal ileum. Part 2: A clinico-statistical study. Gastroenterol Endosc (Japan) 27: 326–336, 1985.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1988

Authors and Affiliations

  • Jacques Pappo
    • 1
  • Robert L. Owen
  1. 1.Cell Biology and Aging Section (151E)Veterans Administration Medical CencterSan FranciscoUSA

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