Abstract
Type I hypersensitivity, which functions to protect the organism from parasites, is caused by binding of antigen to IgE antibodies pre-attached to the cell surface of tissue mast cells and their circulating counterparts, the basophils. In “allergy,” type I hypersensitivity is inappropriately induced by protein-based foreign substances (such as pollen) or protein components of insect stings, which in the normal course of events would be cleared from the organism without causing any damage. Paradoxically, a successful clinical treatment of allergy involves repeated immunization of allergic persons with low doses of the allergen—immunotherapy. Investigation of the available experimental evidence leads to the conclusion that the phenomena of immunotherapy are best addressed in terms of the interplay among the mechanism(s) of immune memory—Th1/Th2 cross-regulation—and the physical compart-mentalization of the immune system. These conclusions are illustrated with a numerical simulation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbas, A. K., A. H. Lichtman and J. S. Pober. 1991.Cellular and Molecular Immunology. Philadelphia, PA: W. B. Sanders Co.
Coffman, R. L. and J. Carty. 1986. A T cell activity that enhances polyclonal production of IgE and its inhibition by interferon-γ.J. Immunol. 136, 949–954.
Daëron, M., S. Latour, O. Malbec, E. Espinosa, P. Pina, S. Pasmans and W. H. Fridman. 1995. The same tyrosine-based inhibition motif, in the intracytoplasmic domain of FcγRIIB, regulates negatively BCR-, TCR-, and FcF-dependent cell activation.Immunity 3, 635–646.
Dembo M., B. Goldstein, A. K. Sobotka and L. M. Lichtenstein. 1978. Histamine release due to bivalent penicilloyl haptens: control by the number of cross-linked IgE antibodies on the basophil plasma membrane.J. Immunol. 121, 354–358.
Fernandez-Botran, R., V. M. Sanders, T. R. Mosmann and E. S. Vitetta. 1988. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells.J. Exp. Med. 168, 543–558.
Fiorentino, D. F., M. W. Bond and T. R. Mosmann. 1989. Two types of mouse helper T cells. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.J. Exp. Med. 170, 2081–2095.
Fiorentino, D. F., A. Zlotnik, P. Vieira, T. R. Mosmann, M. Howard, K. W. Moore and A. O'Garra. 1991. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells.J. Immunol. 146, 3444–3451.
Fishman, M. A. and A. S. Perelson. 1993. Modeling T cell-antigen presenting cell interactions.J. Theor. Biol. 160, 311–342.
Fishman, M. A. and A. S. Perelson. 1994. Th1/Th2 cross-regulation.J. Theor. Biol. 170, 25–56.
Fishman, M. A. and A. S. Perelson. 1995. Lymphocyte memory and affinity selection.J. Theor. Biol. 173, 241–262.
Golden, D. B. K., M. D. Valentine, A. Kagey-Subotka and L. M. Lichtenstein 1980. Regimens ofHymenoptera venom immunotherapy.Ann. Internal. Med. 92, 620–624.
Graft, D. F., K. C. Schuberth, A. Kagey-Sobotka, K. A. Kwiterovich, Y. Niv, L. M. Lichtenstein and M. D. Valentine. 1987. Assessment of prolonged venom immunotherapy in children.J. Allergy Clin. Immunol. 80, 162–166.
Hosken, M. A., K. Shibuya, A. W. Heath, K. M. Murphy and A. O'Garra. 1995. The effect of antigen dose on CD4+ T-helper cell phenotype development in a T-cell receptor-αβ-transgenic model.J. Exp. Med. 182, 1579–1584.
Ishizaka, K. 1976. Cellular events in the IgE antibody response.Adv. Immunol 23, 1–75.
Kroemer, G., E. Cuende and A. C. Martinez. 1993. Compartmentalization of the peripheral immune system.Adv. Immunol. 53, 157–216.
Lichtenstein, L. M. 1993. Allergy and the immune system.Sci. Amer. Sept., 117–124.
Marsh, D. G., S. H. Hsu, M. Roebber, E. Erlich-Kautzky, L. R. Freidhoff, D. A. Meyers, M. K. Pollard and W. B. Bias. 1982. HLA-Dw2: a genetic marker for human immune response to short ragweed pollen allergen Ra5.J. Exp. Med. 155, 1439–1463.
Mosmann, T. R. and K. W. Moore. 1991. The role of IL-10 in cross-regulation of Th1 and Th2 responses.Immunol. Today 12, A49-A53.
Nabors, G. S., T. Nolan, W. Croop, J. Li and J. P. Farrall. 1996. The influence of the site of parasite inoculation on the development of Th1 and Th2 type immune responses in (BALB/Cxc57B1/6) F1-mice with Leishmania Major.Parasite Immunol. 17, 569–579.
Secrist, H., C. J. Chelen, W. Yan, J. D. Marshall and D. T. Umetsu. 1993. Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals.J. Exp. Med. 178, 2123–2130.
Seder, R. A. and W. E. Paul. 1994. Acquisition of lymphokine-producing phenotype by CD4+ T cells.Ann Rev. Immunol.,12, 635–673.
Tew, J. G., R. P. Phipps and T. E. Mandel. 1980. The maintenance and regulation of the humoral immune response: persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells.Immunol. Rev. 53, 175–201.
Woodruff, J. J., L. M. Clarke and Y. H. Chin, 1987. Specific cell-adhesion mechanisms determining migration pathways of recirculating lymphocytes.Ann. Rev. Immunol. 5, 201–222.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fishman, M.A., Segel, L.A. Modeling immunotherapy for allergy. Bltn Mathcal Biology 58, 1099–1121 (1996). https://doi.org/10.1007/BF02458385
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02458385