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Antigen processing and uptake from the intestinal tract

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Summary

We have attempted, in this discussion, to summarize the processes and evidence for absorption of antigenic macromolecules in both animals and humans, comparing the infant to the adult. The mature gut retains the capacity to absorb macromolecules by an energy-dependent pinocytotic mechanism similar to that described for the transport of immunoglobulins and other enteric antigens in certain mammalian species in the neonatal state. The vast majority of adults show no ill effects as a result of this physiologic phenomenon. However, when increased (pathologic) quantities of antigenic macro-molecules gain access to the body because of a derangement in the intraluminal digestive process, or because of a defect in the mucosal barrier, both of which are present in the immature intestine, macromolecular absorption may be altered and result in either local intestinal or systemic disorders.

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References

  1. Lippard VW, Schloss DM, Johnson PA: Immune reactions induced in infants by intestinal absorption of incompletely digested cow’s milk protein. Am J Dis Child 51:562–574, 1936

    Google Scholar 

  2. Galant SP: Biological and clinical significance of the gut as a barrier to penetration of macromolecules. Clin Ped 15:731–734, 1976

    Article  CAS  Google Scholar 

  3. LeFevre ME, Joel DD: Intestinal absorption of particulate matter. Life Sci 21:1403–1408, 1977

    Article  PubMed  CAS  Google Scholar 

  4. Walker WA: Host defense mechanisms in the gastrointestinal tract. Pediatrics 57:901–906, 1976

    PubMed  CAS  Google Scholar 

  5. Walker WA, Isselbacher KJ: Uptake and transport of macromolecules by the intestine: possible role in clinical disorders. Gastroenterology 67:531–550, 1974

    PubMed  CAS  Google Scholar 

  6. Udall JN: Macromolecular transport across the developing intestine. In Environmental effects on maturation. Cold Spring Harbor Laboratory, Banbury Report II, 1982, 187–198

  7. Udall JN, Walker WA: The physiologic and pathologic basis for transport of macromolecules across the intestinal tract. J Ped Gastro and Nutrition 1:295–301, 1982

    CAS  Google Scholar 

  8. Bienenstock, J: The local immune response. Am J Vet Res 36:488–492, 1975

    PubMed  CAS  Google Scholar 

  9. Block KJ, Bloch DB, Stearns M, Walker WA: Intestinal uptake of macromolecules. VI. Uptake of protein antigen in vivo in normal rats and in rats infected withNippostrongylus brasiliensis or subjected to mild systemic anaphylaxis. Gastroenterology 77:1039–1044, 1979

    Google Scholar 

  10. Bockman DE, Winborn WB: Light and electron microscopy of intestinal ferritin absorption. Observations in sensitized and non-sensitized hamsters (Mesocricetus auratus). Anat Ree 155:603–622, 1966

    Article  Google Scholar 

  11. Clark SL: The ingestion of proteins and colloidal materials by columnar absorptive cells of the small intestine in suckling rats and mice. J Biophys Biochem Cytol 5:41–50, 1959

    Article  PubMed  Google Scholar 

  12. Graney D: The uptake of ferritin by ileal absorptive cells in suckling rats. An electron microscopic study. J Anat 123:227–254, 1968

    Article  CAS  Google Scholar 

  13. Walker WA, Cornell R, Davenport LM, Isselbacher KJ: Macromolecular absorption mechanism of horseradish perioxidase uptake and transport in adult and neonatal rat intestine. J Cell Biol 54:195–205, 1972

    Article  PubMed  CAS  Google Scholar 

  14. Udall JN, Pang K, Fritze L, Kleinman R, Walker WA: Development of gastrointestinal mucosal barrier. I. The effect of age on intestinal permeability to macromolecules. Pediatr Res 15:241–244, 1981

    PubMed  CAS  Google Scholar 

  15. Udall JN, Colony P, Fritze L, Pang K, Trier JS, Walker WA: Development of gastrointestinal mucosal barrier. II. The effect of natural vs artificial feeding on intestinal permeability to macromolecules. Pediatr Res 15:245–249, 1981

    PubMed  CAS  Google Scholar 

  16. Wilson SJ, Walzer M: Absorption of undigested proteins in human beings. Am J Dis Child 50:49–57, 1935

    CAS  Google Scholar 

  17. Grusky FL, Cooke RE: The gastrointestinal absorption of unaltered protein in normal infants and in infants recovering from diarrhea. Pediatrics 16:763–768, 1955

    Google Scholar 

  18. Rothberg RM: Immunoglobulin and specific antibody synthesis during the first weeks of life of premature infants. J Pediatr 75:391–399, 1969

    Article  PubMed  CAS  Google Scholar 

  19. Eastham EJ, Lichauco T, Grady MI, Walker WA: Antigenicity of infant formulas: role of immature intestine in protein permeability. J Pediatr 93:561–564, 1978

    Article  PubMed  CAS  Google Scholar 

  20. Paganelli R, Levinsky RJ: Solid phase radioimmunoassay for detection of circulating food protein antigens in human serum. J Imm Methods 37:333–341, 1980

    Article  CAS  Google Scholar 

  21. Roberton DM, Paganelli R, Dinwiddie R, Levinsky RJ: Milk antigen absorption in the premature and neonate. Arch Dis Child 57:369–372, 1982

    PubMed  CAS  Google Scholar 

  22. Dannaeus A, Inganas M, Johanson SGD, Fouchard T: Intestinal uptake of albumin in malabsorption and food allergy in relation to serum IgG antibody and orally adminstered sodium cromoglycate. Clin Allergy 9:263–270, 1979

    Article  PubMed  CAS  Google Scholar 

  23. Lev R, Orlic D: Uptake of proteins in swallowed amniotic fluid by monkey fetal intestine in utero. Gastroenterology 65:60–68, 1973

    PubMed  CAS  Google Scholar 

  24. Moxey PC, Trier JC: Structural features of the mucosa of human fetal small intestine. Gastroenterology 68:1002–1009, 1975

    Google Scholar 

  25. Bamford DR: Studies in vitro of passage of serum proteins across the intestinal wall of young rats. Proc R Soc Lond (Biol) 166:30–47, 1966

    CAS  Google Scholar 

  26. Clarke RM, Hardy RN: Factors influencing the uptake of (125I) polyvinyl pyrrolidine by the intestine of the young rat. J Physiol London 212:801–807, 1971

    PubMed  CAS  Google Scholar 

  27. Alpers DH, Isselbacher KJ: Protein synthesis by the rat intestinal mucosa: the role of ribo-nuclease. J Biol Chem 242:5617–5620, 1967

    PubMed  CAS  Google Scholar 

  28. Bernstein ID, Ovary Z: Absorption of antigens from the gastrointestinal tract. Int Arch Allergy Appl Immunol 33:521–529, 1968

    PubMed  CAS  Google Scholar 

  29. Bockman DE, Cooper MD: Pinocytosis by epithelium associated with lymphoid follicles in the bursa of fabricius, appendix and Peyer’s patches. An electron microscopy study. Am J Anat 136:455–477, 1973

    Article  PubMed  CAS  Google Scholar 

  30. Casley-Smith JR: The passage of ferritin into jejunal epithelial cells. Experiencia 23:370–371, 1967

    Article  Google Scholar 

  31. Walker WA: Antigen handling by the gut. Arch Dis Child 53:527–531, 1978

    PubMed  CAS  Google Scholar 

  32. 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

    PubMed  CAS  Google Scholar 

  33. Danforth E, Moore RD: Intestinal absorption of insulin in the rat. Endocrinology 65:118–126, 1959

    Article  PubMed  CAS  Google Scholar 

  34. Cornell R, Walker WA, Isselbacher KJ: Small intestinal absorption of horseradish peroxidase. A cytochemical study. Lab Invest 25:42–48, 1971

    PubMed  CAS  Google Scholar 

  35. Korenblat RE, Rothberg RM, Minden P: Immune response of human adults after oral and parenteral exposure to bovine serum albumin. J Allergy 41:226–235, 1968

    Article  PubMed  CAS  Google Scholar 

  36. Owen RL: Sequential uptake of horseradish peroxidase by lymphoid follicle epithelium of Peyer’s patches in the neonatal unobstructed mouse intestine: an ultrastructural study. Gastroenterology 72:440–451, 1976

    Google Scholar 

  37. Hemmings WA: First experience of dietary antigen. Lancet 818, April 12, 1980

  38. Cunningham-Rundles C, Brandeis WE, Good RA, Day NK: Milk precipitins, circulating immune complexes and IgA deficiency. Proc Nat Acad Sci USA 75:3387–3389, 1978

    Article  PubMed  CAS  Google Scholar 

  39. Popper H, Schaffner F: Progress in Liver Diseases. New York, Grane & Stratton, 1972, 201–207

    Google Scholar 

  40. Brown WR, Isobe Y, Nakane PK: Ultrastructural localization of IgA and secretory component (SC) in human intestinal mucosa by immunoperoxidase techniques. Gastroenterology 68:869–673, 1975

    Google Scholar 

  41. Triger DR, Cynamon MH, Wright R: Studies on hepatic uptake of antigen. I. Comparison of inferior vena cava and portal vein routes of immunization. Immunology 25:941–950, 1973

    PubMed  CAS  Google Scholar 

  42. Triger DR, Wright R: Studies on hepatic uptake of antigen. II. The effect of hepatotoxins on the immune response. Immunology 25:951–956, 1973

    PubMed  CAS  Google Scholar 

  43. Orland E, Peppard J, Reynolds J, Hall J: Rapid active transport of immunoglobulin A from blood to bile. J Exp Med 147:588–592, 1978

    Article  Google Scholar 

  44. Jackson GDF, Lemaitre-Coelho I, Vaerman JP, Bazin H, Beckers A: Rapid disappearance from serum of intravenously injected rat myeloma IgA and its secretion into bile. Eur J Imm 8:123–126, 1978

    Article  Google Scholar 

  45. Bazin H, Deckers C, Beckers A, Heremans JF: Transplantable immunoglobulin-secreting tumors in rats. I. General patterns of LOU/WSE strain rat immunocytomas and their monoclonal proteins. Int J Cancer 10:568–580, 1972

    Article  PubMed  CAS  Google Scholar 

  46. Peppard J, Orlans E, Payne AWR, Andrew E: The elimination of circulating complexes containing polymeric IgA by excretion into the bile. Immunology 42:83–89, 1981

    PubMed  CAS  Google Scholar 

  47. Harmatz PR, Kleinman RE, Bunnel BW, Bloch KJ, Walker WA: Hepatobiliary clearance of IgA immune complexes formed in the circulation. Hepatology 2:328–333, 1982

    PubMed  CAS  Google Scholar 

  48. Lemaitre-Coeho I, Jackson GDF, Vaerman JP: Relevance of biliary IgA antibodies in rat intestinal immunity. Eur J Imm 8:459–463, 1978

    Article  Google Scholar 

  49. Waldesbuhl M, Allan R, Meylan A, Isliker H: Anticomplimentary activity of gamma G-immunoglobulins and of their sub units. Immunochemistry 7:185–197, 1970

    Article  PubMed  CAS  Google Scholar 

  50. Vaerman JP, Heremans JF: Effect of neuraminadase and acidification on complement-fixing properties of human IgA and IgG. Int Archs Allergy 34:49–52, 1968

    CAS  Google Scholar 

  51. Stokes CR, Swarbrick ET, Soothill JF: Immune elimination and enhanced antibody responses: functions of circulating IgA. Immunology 40:455–458, 1980

    PubMed  CAS  Google Scholar 

  52. Russell MW, Brown TA, Mestechy J: Role of serum IgA. Hepatobiliary transport of circulating antigens. J Exp Med 153:968–976, 1981

    Article  PubMed  CAS  Google Scholar 

  53. Peppard J, Orlans E, Payne AWR, Andrew E: The elimination of circulating complexes containing polymeric IgA by excretion in the bile. Immunology 42:83, 1981

    PubMed  CAS  Google Scholar 

  54. Socken DJ, Simms ES, Nagy BR, Fisher MM, Underdown BJ: Secretory component-dependent hepatic transport of IgA antibody-antigen complex. J Immunol 127:316–319, 1981

    PubMed  CAS  Google Scholar 

  55. Heremans JF: Immunoglobulin formation and function in different tissues. Curr Top Microbiol Immunol 45:132–136, 1968

    Google Scholar 

  56. Ogra PL, Karzon DT, Righthand F: Immunoglobulin response in serum and secretions after immunization with live and inactivated polio vaccine and natural infection. N Engl J Med 279:893–896, 1968

    Article  CAS  PubMed  Google Scholar 

  57. Tomasi TB Jr, Tan EM, Solomon A: Characteristics of an immune system common to certain external secretions. J Exp Med 121:101–107, 1965

    Article  PubMed  CAS  Google Scholar 

  58. Ogra PL, Karzon DT: The role of immunoglobulins in the mechanism of mucosal immunity to viral infection. Pediatr Clin North Am 17:385–389, 1970

    PubMed  CAS  Google Scholar 

  59. Van Furth R, Aiuti F: Immunoglobulin synthesis by tissues of the gastrointestinal and respiratory tract. Protides Biol Fluids 16:479–484, 1968

    Google Scholar 

  60. Crabbe PA, Heremans JF: The distribution of immunoglobulin containing cells along the human gastrointestinal tract. Gastroenterology 51:305–309, 1966

    PubMed  CAS  Google Scholar 

  61. Lindh E: Increased resistance of immunoglobulin A dimers to proteolytic degradation after binding of secretory component. J Immunol 114:284–288, 1975

    PubMed  CAS  Google Scholar 

  62. Cohn ZA, Benson B: The differentiation of mononuclear phagocytes. Morphology, cytochemistry and biochemistry. J Exp Med 121:153–160, 1965

    Article  PubMed  CAS  Google Scholar 

  63. Walker WA, Isselbacher KJ, Bloch KJ: Intestinal uptake of macromolecules: effect of oral immunization. Science 177:608–610, 1970

    Article  Google Scholar 

  64. Walker WA, Wu M, Isselbacher KJ, Bloch KJ: Intestinal uptake of macromolecules. III. Studies on the mechanism by which immunization interferes with antigen uptake. J Immunol 115:854–861, 1975

    PubMed  CAS  Google Scholar 

  65. Andre C, Lambert R, Bazin H, Heremans JF: Interference of oral immunization with the intestinal absorption of heterologous albumin. Eur J Immunol 4:701–704, 1974

    Article  PubMed  CAS  Google Scholar 

  66. Delire M, Cambiaso CL, Masson PL: Circulating immune complexes in infants fed on cow’s milk. Nature 272:632, 1978

    Article  PubMed  CAS  Google Scholar 

  67. Brambell FWR: The transmission of immunity from mother to young and the catabolism of immunoglobulins. Lancet 2:1087–1093, 1966

    Article  PubMed  CAS  Google Scholar 

  68. Kraehenbuhl JP, Campiche MA: Early stages of intestinal absorption of specific antibodies in the newborn. An ultrastructural, cytochemical and immunological study in the pig, rat and rabbit. J Cell Biol 42:345–365, 1969

    Article  PubMed  CAS  Google Scholar 

  69. Kleinman RE, Harmatz PR, Jacobson LA, Udall JN, Bloch KJ, Walker WA: Passive transplacental immunization: influence on the detection of enteric antigen in the systemic circulation. Ped Res (in press) 1983

  70. Selner JC, Merrill DA, Claman HN: Salivary immunoglobulins and albumin. Development during the newborn period. J Ped 72:685, 1968

    Article  CAS  Google Scholar 

  71. Walker WA: The nature and role of mucosal surface immunity against infection in the newborn. In Lambert HP, Wood CBS, eds, Immunological aspects of infection in the fetus and newborn. New York, Academic Press, 1981, p. 83

    Google Scholar 

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Authors and Affiliations

  1. From the Department of Pediatrics, Harvard Medical School and the Children’s Service Pediatric Gastrointestinal and Nutrition Unit, Massachusetts General Hospital, Boston, Massachusetts

    Ronald E. Kleinman MD & W. Allan Walker

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  1. Ronald E. Kleinman MD
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  2. W. Allan Walker
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Supported in part by Grant AM-31079-02 from the National Institutes of Health.

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Kleinman, R.E., Walker, W.A. Antigen processing and uptake from the intestinal tract. Clin Rev Allerg 2, 25–37 (1984). https://doi.org/10.1007/BF02991209

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