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The development of the mucosal immune system pre- and post-weaning: balancing regulatory and effector function

  • M. Bailey (a1), K. Haverson (a1), C. Inman (a1), C. Harris (a1), P. Jones (a1), G. Corfield (a1), B. Miller (a1) and C. Stokes (a1)...


The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and ‘harmless’ antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).

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Adkins, B, Jones, M, Bu, YR & Levy, RB (2004) Neonatal tolerance revisited again: specific CTL priming in mouse neonates exposed to small numbers of semi- or fully allogeneic spleen cells. European Journal of Immunology 34, 19011909
Bailey, M, Haverson, K, Inman, C, Harris, C, Jones, P, Corfield, G, Miller, B & Stokes, C (2005) The influence of environment on development of the mucosal immune system Veterinary Immunology and Immunopathology
Bailey, M, Haverson, K, Miller, B, Jones, P, Sola, I, Enjuanes, L & Stokes, CR (2004) Effects of infection with transmissible gastroenteritis virus on concomitant immune responses to dietary and injected antigens. Clinical and Diagnostic Laboratory Immunology 11, 337343
Bailey, M, Miller, BG, Telemo, E, Stokes, CR & Bourne, FJ (1993) Specific immunological unresponsiveness following active primary responses to proteins in the weaning diet of pigs. International Archives of Allergy and Applied Immunology 101, 266271
Bailey, M, Plunkett, FJ, Rothkotter, H-J, Vega-Lopez, MA, Haverson, K & Stokes, CR (2001) Regulation of mucosal immune responses in effector sites. Proceedings of the Nutrition Society 60, 18
Bianchi, ATJ, Zwart, RJ, Jeurissen, SHM, Moonen-Leusen, HWM (1992) Development of the B-cell and T-cell compartments in porcine lymphoid organs from birth to adult life – an immunohistological approach. Veterinary Immunology and Immunopathology 33, 201221
Beutler, B & Rehli, M (2002) Evolution of the TIR, tolls and TLRs: Functional inferences from computational biology. Current Topics in Microbiology and Immunology 270, 121
Borsutzky, S, Cazac, BB, Roes, J & Guzman, CA (2004) TGF-beta receptor signaling is critical for mucosal IgA responses. Journal of Immunology 173, 33053309
Brandtzaeg, P & Pabst, R (2004) Let's go mucosal: communication on slippery ground. Trends in Immunology 25, 570577
Brown, TA, Russell, MW & Mestecky, J (1984) Elimination of intestinally absorbed antigen into the bile by IgA. Journal of Immunology 132, 780782
Bu, P, Keshavarzian, A, Stone, DD, Liu, JZ, Le PT, Fisher, S Qiao, L (2001) Apoptosis: One of the mechanisms that maintains unresponsiveness of the intestinal mucosal immune system. Journal of Immunology 166, 63996403
Butcher, EC, Williams, M, Youngman, K, Rott, L & Briskin, M (1999) Lymphocyte trafficking and regional immunity. Advances in Immunology 72, 209253
Butler, JE, Sun, J, Weber, P, Navarro, P & Francis, D (2000) Antibody repertoire development in fetal and newborn piglets. III Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues. Immunology 100, 119130
Challacombe, SJ & Tomasi, TB (1980) Systemic tolerance and secretory immunity after oral immunization. Journal of Experimental Medicine 152, 14591472
Chun, SK, Nam, MS, Goh, JS, Kim, WS, Han, YH & Kim, PH (2004) Kinetics and biological function of transforming growth factor-beta isoforms in bovine and human colostrum. Journal of Microbiology and Biotechnology 14, 12671274
Duchmann, R, Kaiser, I, Hermann, E, Mayet, W, Ewe, K, zum Buschenfelde, K-HM (1995) Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clinical and Experimental Immunology 102, 448455
Duchmann, R, Schmitt, E, Knolle, P, zum, Buschenfelde, KHM Neurath, M (1996) Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies to interleukin-12. European Journal of Immunology 26, 934938
Flajnik, MF, Du Pasquier, L (2004) Evolution of innate and adaptive immunity: can we draw a line. Trends in Immunology 25, 640644
Fujihashi, K, Dohi, T, Rennert, PD, Yamamoto, M, Koga, T, Kiyono, H & McGhee, JR (2001) Peyer's patches are required for oral tolerance to proteins. Proceedings of the National Academy of Sciences USA 98, 3310
Helm, RM & Burks, AW (2000) Mechanisms of food allergy. Current Opinion in Immunology 12, 647653
Holt, PG, Sly, PD & Bjorksten, B (1997) Atopic versus infectious diseases in childhood: a question of balance. Pediatric Allergy and Immunology 8, 5358
Johansen, FE, Braathen, R & Brandtzaeg, P (2001) The J chain is essential for polymeric Ig receptor-mediated epithelial transport of IgA. Journal of Immunology 167, 51855192
Kalliomaki, M, Ouwehand, A, Arvilommi, H, Kero, P & Isolauri, E (1999) Transforming growth factor-beta in breast milk: A potential regulator of atopic disease at an early age. Journal of Allergy and Clinical Immunology 104, 12511257
Kunkel, EJ & Butcher, EC (2002) Chemokines and the tissue-specific migration of lymphocytes. Immunity 16, 14
Levine, AD & Fiocchi, C (2001) Regulation of life and death in lamina propria T cells. Seminars in Immunology 13, 195199
Litman, GF, Anderson, MK & Rast, J (1999) Evolution of antigen binding receptors. Annual Review of Immunology 17, 109147
Luo, C & Zheng, L (2000) Independent evolution of Toll and related genes in insects and mammals. Immunogenetics 51, 9298
McDermott, MR & Bienenstock, J (1979) Evidence for a common mucosal immunological system. 1. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. Journal of Immunology 122, 18921898
MacPherson, AJ & Uhr, T (2004a) Compartmentalization of the mucosal immune responses to commensal intestinal bacteria. Annals of the New York Academy of Sciences 1029, 3643
MacPherson, AJ & Uhr, T (2004b) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 16621665
Manzano, M, Abadia-Molina, AC, Garcia-Olivares, E, Gil, A & Rueda, R (2002) Absolute counts and distribution of lymphocyte subsets in small intestine of BALB/c mice change during weaning. Journal of Nutrition 132, 27572762
Miller, BG, Whittemore, CT, Stokes, CR & Telemo, E (1994) The effect of delayed weaning on the development of oral tolerance to soybean protein in pigs. British Journal of Nutrition 71, 615625
Mowat, AM, Parker, LA, Beacock-Sharp, H, Millington, OR & Chirdo, F (2004) Oral tolerance: Overview and historical perspectives. Annals of the New York Academy of Sciences 1029, 18
Ogawa, J, Sasahara, A, Yoshida, T, Sira, MM, Futatani, T, Kanegane, H & Miyawaki, T (2004) Role of transforming growth factor-beta in breast milk for initiation of IgA production in newborn infants. Early Human Development 77, 6775
Oz, HS, Ray, M, Chen, TS & McClain, CJ (2004) Efficacy of a transforming growth factor 82 containing nutritional support formula in a murine model of inflammatory bowel disease. Journal of the American College of Nutrition 23, 220226
Peng, HJ, Turner, MW & Strobel, S (1989) Failure to induce oral tolerance to protein antigens in neonatal mice can be corrected by transfer of adult spleen-cells. Pediatric Research 26, 486490
Peng, YF, Laouar, Y, Li, MO, Green, EA & Flavell, RA (2004) TGF-beta regulates in vivo expansion of Foxp3-expressing CD4(+)CD25(+) regulatory T cells responsible for protection against diabetes. Proceedings of the National Academy of Sciences USA 101, 45724577
Phillips-Quagliata, JM (2002) Adhesion molecules and circulation and differentiation of lymphocytes in GALT and mammary glands. In Food Allergy and Intolerance, chapter 4 [Brostoff, J, Challacombe, SJ, editors]. London: Saunders.
Prioult, G, Fliss, I & Pecquet, S (2003) Effect of probiotic bacteria on induction and maintenance of oral tolerance to beta-lactoglobulin in gnotobiotic mice. Clinical and Diagnostic Laboratory Immunology 10, 787792
Rothkotter, HJ, Ulbrich, H & Pabst, R (1991) The postnatal-development of gut lamina propria lymphocytes – number, proliferation, and T-cell and B-cell subsets in conventional and germ-free pigs. Pediatric Research 29, 237242
Sait, L, Galic, M, Strugnell, RA & Janssen, PH (2003) Secretory antibodies do not affect the composition of the bacterial microbiota in the terminal ileum of 10-week-old mice. Applied and Environmental Microbiology 69, 21002109
Samsom, JN (2004) Regulation of antigen-specific regulatory T-cell induction via nasal and oral mucosa. Critical Reviews in Immunology 24, 157177
Schroder, HC, Ushijima, H, Krasko, A, Gamulin, V, Thakur, NL, Diehl-Seifert, B, Muller, IM & Muller, WEG (2003) Emergence and disappearance of an immune molecule, an antimicrobial lectin, in basal Metazoa – A tachylectin-related protein in the sponge Suberites domuncula. Journal of Biological Chemistry 278, 3281032817
Spahn, TW, Fontana, A, Faria, AMC, Slavin, AJ, Eugster, HP, Zhang, XM, Koni, PA, Ruddle, NH, Flavell, RA, Rennert, PD & Weiner, HL (2001) Induction of oral tolerance to cellular immune responses in the absence of Peyer's patches. European Journal of Immunology 31, 1278
Stagg, AJ, Kamm, MA & Knight, SC (2002) Intestinal dendritic cells increase T cell expression of alpha 4 beta 7 integrin. European Journal of Immunology 32, 14451454
Stokes, CR, Newby, TJ & Bourne, FJ (1983a) The influence of oral immunisation on local and systemic immune responses to heterologous antigens. Clinical and Experimental Immunology 52, 399406
Stokes, CR, Swarbrick, ET & Soothill, JF (1983b) Genetic differences in immune exclusion and partial tolerance to ingested antigens. Clinical and Experimental Immunology 52, 678684
Talham, GL, Jiang, HQ, Bos, NA & Cebra, JJ (1999) Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infection and Immunity 67, 19922000
Teillet, F, Dublet, B, Andrieu, JP, Gaboriaud, C, Arland, GJ & Thielens, NM (2005) The two major oligomeric forms of human mannan-binding lectin: Chemical characterization, carbohydrate-binding properties, and interaction with MBL-associated serine proteases. Journal of Immunology 174, 28702877
van den, Biggelaar, AHJ, van, Ree, R, Rodrigues, LC, Lell, B, Deelder, AM, Kremsner, PG & Yazdanbakhsh, M (2000) Decreased atopy in children infected with Schistosoma haematobium : a role for parasite-induced interleukin-10. Lancet 356, 17231727
Vega-Lopez, MA, Bailey, M, Telemo, E & Stokes, CR (1995) Effect of early weaning on the development of immune cells in the pig small-intestine. Veterinary Immunology and Immunopathology 44, 319327
Vega-Lopez, MA, Telemo, E, Bailey, M, Stevens, K & Stokes, CR (1993) Immune cell distribution in the small-intestine of the pig – immunohistological evidence for an organized compartmentalization in the lamina propria. Veterinary Immunology and Immunopathology 37, 4960
Wilson, AD, Haverson, K, Southgate, K, Bland, PW, Stokes, CR & Bailey, M (1996) Expression of major histocompatibility complex class II antigens on normal porcine intestinal endothelium. Immunology 88, 98103
Xu, RJ, Doan, QC & Regester, GO (1999) Detection and characterisation of transforming growth factor-beta in porcine colostrum. Biology of the Neonate 75, 5964
Zapata, AG & Cooper, EL (1990) The Immune System: Comparative Histophysiology. Chichester, West Sussex: John Wiley.


The development of the mucosal immune system pre- and post-weaning: balancing regulatory and effector function

  • M. Bailey (a1), K. Haverson (a1), C. Inman (a1), C. Harris (a1), P. Jones (a1), G. Corfield (a1), B. Miller (a1) and C. Stokes (a1)...


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