Abstract
There is considerable evidence that the mucosal or secretory immune response in the gastrointestinal tract is compromised by aging. The generation of a mucosal immune response is an extremely complex process that involves antigenic stimulation of a specific subpopulation of immunologically competent cells in the Peyer's patches, differentiation and migration of these cells to the small intestinal lamina propria, initiation and regulation of local antibody production in the intestinal wall, and mucosal epithelial cell receptor-mediated transport of antibodies to the intestinal lumen. Available data suggest that gastrointestinal mucosal immunosenescence reflects deficits in: (1) the differentiation and/or migration (homing) of immunoglobulin A immunoblasts to the intestinal lamina propria, and (2) the initiation and/or regulation of local antibody production. The significant age-related increases in the incidence and severity of gastrointestinal infectious diseases, coupled with the potential for immunopharmacologic manipulation of the mucosal immune compartment, substantiate the merit of studies designed to resolve the etiology of mucosal immunodeficiency in the elderly.
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References
Makinodan T, Kay M: Age influences on the immune system. Adv Immunol 29:287–330, 1980
Schmucker DL, Daniels CK: Aging, gastrointestinal infections and mucosal immunity. J Am Geriatr Soc 34:377–384, 1985
Arranz E, Ferguson A: Ageing and gastrointestinal immunity. Eur J Gastroenterol Hepatol 4:1–14, 1992
Batory G, Jansco A, Puskas E: Antibody and immunoglobulin levels in aged humans. Arch Gerontol Geriatr 3:175–179, 1984
Stowe SP, Redman SR, Segal HL, Stormont JM, Chessin LN, Shah AN, Chey WY: Characteristics and natural history of IBD in the elderly—analysis of Rochester (NY) community.In Inflammatory Bowel Disease. R McDermott (ed). Amsterdam, Elsevier Scientific, 1988, pp 649–654
Powers DC: Immunological principles and emerging strategies of vaccination for the elderly. J Am Geriatr Soc 40:81–94, 1992
Beyer WE, Palache AM, Baljet M: Antibody induction by influenza vaccines in the elderly: A review of the literature. Vaccine 7:385–394, 1989
Waldman RH, Bergmann K, Stone J: Age-dependent antibody response in mice and humans following oral influenza immunization. J Clin Immunol 7:327–332, 1987
Ganguly R, Stablein J, Lockey RF: Defective antimicrobial functions of oral secretions in the elderly. J Infect Dis 153:163–164, 1986
Strassburg MA, Greenland S, Sorvillo FJ: Influenza in the elderly: Report of an outbreak and a review of vaccine effectiveness reports. Vaccine 4:38–44, 1986
Ship JA, Wolff A, Selik RM: Epidemiology of acquired immune deficiency syndrome in persons aged 50 years or older. J Acquir Immune Defic Syndr 4:84–88, 1991
Weiler PG, Mungas D, Pomersantz S: AIDS as a cause of dementia in the elderly. J Am Geriatr Soc 36:139–141, 1988
Sutin DG, Rose DN, Mulvihill M, Taylor B: Survival of elderly patients with transfusion-related acquired immunodeficiency syndrome. J Am Geriatr Soc 41:214–216, 1993
Phillips AN, Lee CA, Elford J, Webster A, Janossy G, Timms A, Bofill M, Kernoff P: More rapid progression to AIDS in older HIV-infected people: The role of CD4+ T cell counts. J Acquir Immune Defic Syndr 4:970–975, 1991
Blaxhult A, Granath F, Lidman K, Giesecke J: The influence of age on the latency period to AIDS in people infected by HIV through blood transfusion. J Acquir Immune Defic Syndr 4:125–129, 1990
Horan ME: Immunosenescence and mucosal immunity. Lancet 341:793–794, 1993
Gross PA, Quinnan GV Jr, Weksler ME: Relation of chronic disease and immune response to influenza vaccine in the elderly. Vaccine 7:303–308, 1989
Chandra RK: Mucosal immune responses in malnutrition. Ann NY Acad Sci 409:345–351, 1983
Watson RR, McMurray DN, Martin P: Effect of age, malnutrition and renutrition on free secretory component and IgA secretions. Am J Clin Nutr 42:281–288, 1985
Ebersole JL, Smith DJ, Taubman MA: Secretory immune responses in aging rats. I. Immunoglobulin levels. Immunology 56:345–350, 1985
Amman AJ, Schiffman G, Austrian R: The antibody responses to pneumococcal capsular polysaccharides in aged individuals. Proc Soc Exp Biol Med 164:312–316, 1980
Buckley CE, Buckley EG, Dorsey FC: Longitudinal changes in serum immunoglobulin levels in older humans. Proc Soc Exp Biol Med 33:2023–2028, 1974
Finkelstein MS, Tanner M, Freedman MC: Salivary and serum IgA levels in a geriatric outpatient population. J Clin Immunol 4:85–89, 1984
Arranz E, O'Mahony S, Barton JR, Ferguson A: Immunosenescence and mucosal immunity: Significant effects of old age on secretory IgA concentrations and intraepithelial lymphocyte counts. Gut 33:882–886, 1992
Taylor LD, Daniels CK, Schmucker DL: Ageing compromises gastrointestinal mucosal immune response in the rhesus monkey. Immunology 75:614–618, 1992
Vajdy M, Lycke NY: Cholera toxin adjuvant promotes long-term immunological memory in the gut mucosa to unrelated immunogens after oral immunization. Immunology 75:488–492, 1992
Smith D, Ebersole J, Taubman M: Local and systemic immune response in aged hamsters. Immunology 50:407–413, 1983
Fujimoto K, Terao K, Cho F: Age-related immunoglobulin levels in cynomolgus monkeys. Jpn J Med Sci Biol 35:17–23, 1981
Senda S, Cheng E, Kawanishi H: Aging associated changes in murine intestinal immunoglobulin A and M secretions. Scand J Immunol 27:157–164, 1988
Steffen MJ, Ebersole JL: Effects of aging on antibody avidity toMycoplasma pulmonis. Mech Aging Dev 78:123–144, 1995
Schmucker DL, Daniels CK, Wang RK, Smith K: Mucosal immune response to cholera toxin in ageing rats. I. Antibody and antibody-containing cell response. Immunology 64:691–695, 1988
Green-Johnson JM, Haq JA, Szewczuk MR: Effects of aging on the production of cytoplasmic interleukin-4 and -5 and interferon-γ by mucosal and systemic lymphocytes after activation with phytohemagglutinin. Aging Immunol Infect Dis 3:43–57, 1991
Kang D, Ohkawa S, Difabio S, Merrill K, Fujihashi K, Yamamoto M, Miller CJ, Mathas M, McGhee JR, Eldridge JH, Murphey-Corb M, Kiyono H: Characterization of T and B cells isolated from mucosa-associated tissues of the rhesus macque. Cell Immunol 151:379–391, 1993
Kawanishi J, Kiely J: Immune related alterations in aged gut-associated lymphoid tissues in mice. Dig Dis Sci 34:175–184, 1989
Cornes JS: Number, size and distribution of Peyer's patches in the human small intestine. Gut 6:225–230, 1965
Bianchi A, van der Heijden PJ, Stok W, Rozing J, Coolen C: Decrease of IgA-secreting cells in the lamina propria of mice during aging. Aging Immunol Infect Dis 2:241–250, 1990
Fleming AL, Field EH, Tolaymat N, Cowdery J: Age influences recovery of systemic and mucosal immune responses following acute depletion of CD4 T cells. Clin Immunol Immunopath 69:285–291, 1993
Bienenstock J, Befus D, McDermott M: Regulation of lymphoblastic traffic and localization in mucosal tissues with emphasis on IgA. Fed Proc 42:3213–3217, 1984
Haaijman JJ, Schuit HR, Hijmans W: Immunoglobulin-containing cells in different lymphoid organs of the CBA mouse during its lifespan. Immunology 32:427–434, 1977
Kawanishi H, Kiely J: Immunoregulatory defects in murine aged Peyer's patches. Eur J Immunol 17:1223–1228, 1987
Ebersole JL, Steffen MJ, Pappo J: Secretory immune responses in ageing rats. II. Phenotype distribution of lymphocytes in secretory and lymphoid tissues. Immunology 64:289–294, 1988
Daniels CK, Perez P, Schmucker DL: Alterations in CD8+ cell distribution in gut-associated lymphoid tissues (GALT) of the aging Fischer 344 rat: A correlated immunohistochemical and flow cytometric analysis. Exp Gerontol 28:549–555, 1993
Crowley CA, Wade AW, Szewczuk MR: Divergent shifts in T-lymphocyte subpopulations among mucosal lymphoid tissues of mice with increasing age. Ann NY Acad Sci 409:806–807, 1983
Ernst DN, Weigle WO, Thoman M: Retention of T cell reactivity to mitogens and alloantigens by Peyer's patch cells of aged mice. J Immunol 138:26–31, 1987
Szewczuk MR, Wade AW: Aging and the mucosal-associated lymphoid system. Ann NY Acad Sci 409:333–344, 1983
Green-Johnson JM, Szewczuk MR: Proliferative capacity of senescent lymphocytes. II. Monoclonal antibody stimulation of mucosal and systemic lymphocytes via T cell activation molecules, CD3 epsilon, T cell receptor Vβ chain and phosphatidylinositol-linked anchored receptors THY-1 and LY-6A.2/TAP. Reg Immunol 3:323–327, 1990
Wade AW, Green-Johnson JM, Szewczuk MR: Functional changes in systemic and mucosal lymphocyte repertoires with age: an update review. Aging Immunol Infect Dis 1:65–97, 1988
van der Heijden PJ, Bianchi AT, Stok W, Bockhout BA: Background (spontaneous) immunoglobulin production in the murine small intestine as a function of age. Immunology 65:243–248, 1988
Szewczuk MR, Campbell RJ, Jung LK: Lack of age-associated immune dysfunction in mucosal-associated lymph nodes. J Immunol 126:2200–2204, 1981
Rivier DA, Trefts PE, Kagnoff MF: Age-dependence of the IgA anti-α(1–3) Dextran B1355 responsein vitro. Scand J Immunol 17:115–121, 1983
Daniels CK, Schmucker DL, Irvin BJ: Differential IgA responses in the aging Fischer rat following mucosal stimulation with cholera toxin orβ subunit. Aging Immunol Infect Dis 4:95–107, 1993
Mega J, McGhee JR, Kiyono H: Cytokine and Ig-producing cells in mucosal effector tissues: Analysis of IL-5 and IFN-γ-producing T cells, T cell receptor expression and IgA plasma cells from mouse salivary gland-associated tissues. J Immunol 148:2030–2039, 1992
Fujihashi K, McGhee JR, Cummins L, Beagley KW, Taga T, Hirano T, Kishimoto T, Mestecky J, Kiyono H: Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis. J Clin Invest 88:248–252, 1991
McGhee JR, Mestecky J, Elson CO, Kiyono H: Regulation of IgA synthesis and immune response by T cells and interleukins. J Clin Immunol 9:175–199, 1989
Kono Y, Beagley KW, Fujihashi K, McGhee JR, Mestecky J, Kiyono H: Cytokine regulation of localized inflammation. Induction of activated B cells and IL-6-mediated polyclonal IgG and IgA synthesis in inflamed human gingiva. J Immunol 146:181–191, 1991
Cowdry JS, Kemp JD, Ballas ZK, Weber SP: Interleukin-1 induces T cell-mediated differentiation of murine Peyer's patch B cells to IgA secretion. Reg Immunol 1:9–14, 1988
Stanisz AM, Befus D, Bienenstock J: Differential effects of vasoactive intestinal peptide, substance P and somatostatin on immunoglobulin synthesis and lymphocyte proliferation by lymphocytes from Peyer's patches, mesenteric lymph nodes and spleen. J Immunol 136:152–156, 1986
Ottaway CA: Neuroimmunomodulation in the intestinal mucosa. Gastroenterol Clin North Am 20:511–529, 1991
Ershler WB: Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc 41:176–181, 1993
Underdown BJ, Schiff JM: Immunoglobulin A: strategic defense initiative at the mucosal surface. Annu Rev Immunol 4:389–417, 1986
Daniels CK, Schmucker DL: Secretory component-dependent binding of immunoglobulin A in the rat, monkey and human: A comparison of intestine and liver. Hepatology 7:517–521, 1987
Brown WR, Kloppel TM: The liver and IgA: immunological, cell biological and clinical implications. Hepatology 9:763–784, 1989
Brandtzaeg P: Role of J chain and secretory component in receptor-mediated glandular and hepatic transport of immunoglobulins in man. Scand J Immunol 22:111–146, 1985
Larkin JM, Sztul ES, Palade GE: Phosphorylation of the rat hepatic polymeric IgA receptor. Proc Natl Acad Sci USA 83:4759–4763, 1986
Casanova JE, Breitfeld PP, Ross SA, Mostov K: Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis. Science 248:742–745, 1991
Renston RH, Jones AL, Christianson WD, Hradek GT: Evidence for vesicular transport in hepatocytes for biliary secretion of immunoglobulin A. Science 208:1276–1280, 1980
Musil LA, Baenziger J: Cleavage of membrane secretory component to soluble component occurs on the cell surface of rat hepatocyte monolayers. J Cell Biol 104:1725–1733, 1987
Lindh E: Increased resistance of immunoglobulin A dimers to proteolytic degradation after binding of secretory component. J Immunol 114:284–286, 1975
Schmucker DL, Gilbert R, Jones AL, Hradek GT, Bazin H: Effect of aging on the hepatobiliary transport of dimeric immunoglobulin A in the male Fischer rat. Gastroenterology 88:436–443, 1985
Goldman IS, Jones AL, Hradek GT, Huling S: Hepatocyte handling of immunoglobulin A in the rat: the role of microtubules. Gastroenterology 85:130–140, 1983
Taylor LD, Jones AL, Schmucker DL: Does aging affect liver microtubules? Proc Soc Exp Biol Med 199:441–445, 1992
Daniels CK, Schmucker DL, Jones AL: Age-dependent loss of dimeric immunoglobulin A receptors in the liver of the Fischer 344 rat. J Immunol 134:3855–3858, 1985
Gregoire CD, Zhang L, Daniels CK: Expression of the polymeric immunoglobulin receptor by cultured aged rat hepatocytes. Gastroenterology 103:296–301, 1992
van Bezooijen RL, Wang RK, Lechner MC, Schmucker DL: Aging affects the regulation of preferentially expressed liver proteins in male Fischer 344 rats. Exp Gerontol 29:186–196, 1994
Daniels CK, Schmucker DL, Jones AL: Hepatic asialoglycoprotein receptor-mediated binding of human polymeric immunoglobulin A. Hepatology 9:229–234, 1989
Daniels CK, Schmucker DL, Bazin H, Jones AL: Immunoglobulin A receptor of rat small intestinal enterocytes is unaffected by aging. Gastroenterology 94:1432–1440, 1988
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Some of the research described in this review was supported by the Department of Veterans Affairs and the USPHS (NIH) and the American Federation for Aging Research.
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Schmucker, D.L., Heyworth, M.F., Owen, R.L. et al. Impact of aging on gastrointestinal mucosal immunity. Digest Dis Sci 41, 1183–1193 (1996). https://doi.org/10.1007/BF02088236
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DOI: https://doi.org/10.1007/BF02088236