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Stimulation of Mucosal Immunity

  • David J. M. Lewis
  • Christopher M. M. Hayward
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 87)

Abstract

The mucosal immune system is composed of distinct regional immune tissue (e.g., “GALT,” gut-associated lymphoid tissue; “NALT,” nasal-associated lymphoid tissue; “BALT,” bronchus-associated lymphoid tissue; reproductive tract, and breast tissue) interconnected by trafficking of primed lymphocytes as a common “mucosa-associated lymphoid tissue” (“MALT”) (1). In addition, immune responses within MALT may occur independently of systemic immunity, with distinctive regulatory mechanisms and the induction of dimeric secretory IgA (SIgA) at the mucosal surface. As a result, traditional methods for inducing systemic immunity may not induce significant SIgA, and techniques have been developed to deliver antigen directly to a mucosal surface in such a way as to induce immunity rather than immunological tolerance. The trafficking of primed B- and T-cells between mucosal sites, regulated by specific adhesion molecules, such as α4β7 integrin on lymphocytes and MAdCAM-l on mucosal blood vessels (2), leads to dissemination of the mucosal immune response. One benefit of this is that immunization of an accessible mucosal surface may induce an immune response at less accessible mucosal sites (such as the genital tract). Furthermore, by characterizing mucosa-homing lymphocytes trafficking in the blood, it may be possible to indirectly study mucosal responses.

Keywords

Cholera Toxin ELIspot Assay Mucosal Immune Response Cholera Vaccine Mucosal Response 
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.

References

  1. 1.
    Czerkinsky, C. and Holmgren, J. (1994) Exploration of mucosal immunity in humans; relevance to vaccine development. Cell. Mol. Biol. 1, 37–44.Google Scholar
  2. 2.
    Quiding, J. M., Lakew, M., Nordstrom, I., Banchereau, J., Butcher, E., Holmgren, J., et al. (1995) Human circulating specific antibody-forming cells after systemic and mucosal immunizations: differential homing commitments and cell surface differentiation markers. Eur. J. Immunol. 25, 322–327.CrossRefGoogle Scholar
  3. 3.
    Holmgren, J., Svennerholm, A. M., Jertborn, M., Clemens, J., Sack, D. A., Salenstedt, R., et al. (1992) An oral B subunit: whole cell vaccine against cholera. Vaccine 10, 911–914.PubMedCrossRefGoogle Scholar
  4. 4.
    Lewis, D. J., Novotny, P., Dougan, G., and Griffin, G. E. (1991) The early cellular and humoral immune response to primary and booster oral immunization with cholera toxin B subunit. Eur. J. Immunol. 21, 2087–2094.PubMedCrossRefGoogle Scholar
  5. 5.
    Lewis, D. J., Gilks, C. F., Ojoo, S., Castello, B. L., Doughy, G., Evans, M. R., et al. (1994) Immune response following oral administration of cholera toxin B subunit to HIV-1-infected UK and Kenyan subjects. AIDS 8, 779–785.PubMedCrossRefGoogle Scholar
  6. 6.
    Eriksson, K., Kilander, A., Hagberg, L., Norkrans, G., Holmgren, J., and Czerkinsky, C. (1993) Intestinal antibody responses to oral vaccination in HIV-infected individuals. AIDS 7, 1087–1091.PubMedCrossRefGoogle Scholar
  7. 7.
    Holmgren, J., Lycke, N., and Czerkinsky, C. (1993) Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen vector systems. Vaccine 11, 1179–1184.PubMedCrossRefGoogle Scholar
  8. 8.
    Pizza, M., Giuliani, M. M., Fontana, M. R., Monaci, E., Douce, G., Dougan, G., et al. (2001) Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine 19, 2534–2541.PubMedCrossRefGoogle Scholar
  9. 9.
    Roberts, M., Bacon, A., Rappuoli, R., Pizza, M., Cropley, I., Douce, G., et al. (1995) A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins. Infect. Immun. 63, 2100–2108.PubMedGoogle Scholar
  10. 10.
    Douce, G., Turcotte, C., Cropley, I., Roberts, M., Pizza, M., Domenghini, M., et al. (1995) Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proc. Natl. Acad. Sci. USA 92, 1644–1648.PubMedCrossRefGoogle Scholar
  11. 11.
    Bergquist, C., Lagergard, T., Lindblad, M., and Holmgren, J. (1995) Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates. Infect. Immun. 63, 2021–2025.PubMedGoogle Scholar
  12. 12.
    O’ Hagan, D. T., McGee, J. P., Holmgren, J., Mowat, A. M., Donachie, A. M., Mills, K. H., et al. (1993) Biodegradable microparticles for oral immunization. Vaccine 11, 149–154.CrossRefGoogle Scholar
  13. 13.
    Kutteh, W. H., Kantele, A., Moldoveanu, Z., Crowley-Nowick, P. A., and Mestecky, J. (2001) Induction of specific immune responses in the genital tract of women after oral or rectal immunization and rectal boosting with Salmonella typhi Ty 21a vaccine. J. Reprod. Immunol. 52(1–2), 61–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Kantele, A., Westerholm, M., Kantele, J. M., Makela, P. H., and Savilahti, E. (1999) Homing potentials of circulating antibody-secreting cells after administration of oral or parenteral protein or polysaccharide vaccine in humans. Vaccine 17(3), 229–236.PubMedCrossRefGoogle Scholar
  15. 15.
    Kantele, A., Hakkinen, M., Moldoveanu, Z., Lu, A., Savilahti, E., Alvarez, R. D., et al. (1998) Differences in immune responses induced by oral and rectal immunizations with Salmonella typhi Ty21a: evidence for compartmentalization within the common mucosal immune system in humans. Infect. Immun. 66(12), 5630–5635.PubMedGoogle Scholar
  16. 16.
    Quiding, J. M., Granstrom, G., Nordstrom, I., Holmgren, J., and Czerkinsky, C. (1995) Induction of compartmentalized B-cell responses in human tonsils. Infect. Immun. 63, 853–857.Google Scholar
  17. 17.
    Cripps, A. W., Dunkley, M. L., and Clancy, R. L. (1994) Mucosal and systemic immunizations with killed Pseudomonas aeruginosa protect against acute respiratory infection in rats. Infect. Immun. 62, 1427–1436.PubMedGoogle Scholar
  18. 18.
    Lehner, T., Bergmeier, L. A., Tao, L., Panagiotidi, C., Klavinskis, L. S., Hussain, L., et al. (1994) Targeted lymph node immunization with simian immunodeficiency virus p27 antigen to elicit genital, rectal, and urinary immune responses in nonhuman primates. J. Immunol. 153, 1858–1868.PubMedGoogle Scholar
  19. 19.
    Lue, C., van den Wall Bake, A. W., Prince, S. J., Julian, B. A., Tseng, M. L., Radl, J., et al. (1994) Intraperitoneal immunization of human subjects with tetanus toxoid induces specific antibody-secreting cells in the peritoneal cavity and in the circulation, but fails to elicit a secretory IgA response. Clin. Exp. Immunol. 96, 356–363.PubMedCrossRefGoogle Scholar
  20. 20.
    Castello-Branco, L. R. R., Griffin, G. E., Poulton, T. A., Dougan, G., and Lewis, D. J. M. (1994) Characterization of the circulating T cell response after oral immunisation of human volunteers with cholera toxin B subunit. Vaccine 12, 65–72.PubMedCrossRefGoogle Scholar
  21. 21.
    McNeela, E. A., O’Connor, D., Jabbal-Gill, I., Illum, L., Davis, S. S., Pizza, M., et al. (2000) A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery. Vaccine 19, 1188–1198.PubMedCrossRefGoogle Scholar
  22. 22.
    Castello-Branco, L. R. R., Griffin, G. E., Dougan, G., and Lewis, D. J. M. (1995) A method to screen T lymphocyte epitopes after oral immunisation of humans: application to cholera toxin B subunit. Vaccine 13, 817–820.PubMedCrossRefGoogle Scholar
  23. 23.
    Lagoo, A. S., Eldridge, J. H., Lagoo, D. S., Black, C. A., Ridwan, B. U., Hardy, K. J., et al. (1994) Peyer’s patch CD8+ memory T cells secrete T helper type 1 and type 2 cytokines and provide help for immunoglobulin secretion. Eur. J. Immunol. 24, 3087–3092.PubMedCrossRefGoogle Scholar
  24. 24.
    Hiroi, T., Fujihashi, K., McGhee, J. R., and Kiyono, H. (1994) Characterization of cytokine-producing cells in mucosal effector sites: CD3+ T cells of Thl and Th2 type in salivary gland-associated tissues. Eur. J. Immunol. 24, 2653–2658.PubMedCrossRefGoogle Scholar
  25. 25.
    Rudin, A., Johansson, E. L., Bergquist, C., and Holmgren, J. (1998) Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans. Infect. Immun. 66, 3390–3396.PubMedGoogle Scholar
  26. 26.
    Johansson, E. L., Wassen, L., Holmgren, J., Jertborn, M., and Rudin, A. (2001) Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect. Immun. 69, 7481–7486.PubMedCrossRefGoogle Scholar
  27. 27.
    Isaka, M., Yasuda, Y., Kozuka, S., Taniguchi, T., Matano, K., Maeyama, J., et al. (1999) Induction of systemic and mucosal antibody responses in mice immunized intranasally with aluminium-non-adsorbed diphtheria toxoid together with recombinant cholera toxin B subunit as an adjuvant. Vaccine 18, 743–751.PubMedCrossRefGoogle Scholar
  28. 28.
    Illum, L., Jabbal-Gill, I., Hinchcliffe, M., Fisher, A. N., and Davis, S. S. (2001) Chitosan as a novel nasal delivery system for vaccines. Adv. Drug Deliv. Rev. 51, 81–96.PubMedCrossRefGoogle Scholar
  29. 28a.
    Mills, K., Cosgrove, C., McNeela, E. A., et al. (2003) Protective diptheria immunity induced in healthy volunteers by unilateral prime-boost intranasal immunization associated with ipsilateral mucusal secretory IgA. Infect. Immun. 71(2), 726–732.PubMedCrossRefGoogle Scholar
  30. 29.
    Marcello, A., Loregian, A., Palu, G., and Hirst, T. R. (1994) Efficient extracellular production of hybrid Escherichia coli heat-labile enterotoxin B subunits in a marine vibrio. FEMS Microbiol. Lett. 117, 47–51.PubMedCrossRefGoogle Scholar
  31. 30.
    Hashar, T. H. and Hirst, T. R. (1995) Immunoregulatory role of H-2 and intra-H-2 alleles on antibody responses to recombinant preparations of B-subunits of Escherichia coli heat labile enterotoxin (rEtxB) and cholera toxin (rCtxB). Vaccine 13, 803–810.CrossRefGoogle Scholar
  32. 31.
    Schaefer, M. E., Rhodes, M., Prince, S. J., Michalek, S. M., and McGhee, J. R. (1977) A plastic intraoral device for the collection of human parotid saliva. J. Dent. Res. 56, 728–733.CrossRefGoogle Scholar
  33. 32.
    Gaspari, M. M., Brennan, P. T., Solomon, S. M., and Elson, C. O. (1988) A method of obtaining, processing, and analyzing human intestinal secretions for antibody content. J. Immunol. Methods 110, 85–91.PubMedCrossRefGoogle Scholar
  34. 33.
    de Vos, T. and Dick, T. A. (1991) A rapid method to determine the isotype and specificity of coproantibodies in mice infected with Trichinella or fed cholera toxin. J. Immunol. Methods 141, 285–288.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2003

Authors and Affiliations

  • David J. M. Lewis
    • 1
  • Christopher M. M. Hayward
    • 1
  1. 1.Department of Cellular Molecular Clinical MedicineSt. George’s Hospital Medical SchoolLondonUK

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