Abstract
Exposure of cells of the lymphoid system to endotoxin in conjunction with conventional antigens results in a dramatic modification of the specific immune response that would otherwise occur. Johnson et al. (1956) initially observed that endotoxin administered concomitantly with protein antigens resulted in markedly increased antibody titers. The effect could be obtained using endotoxin prepared from several species of gram-negative bacteria. The ability of endotoxin to thus act as a conventional adjuvant was found to depend on the time of administration relative to antigen, as demonstrated by Kind and Johnson (1959) and Franzi and McMaster (1968). They showed that enhanced antibody responses occurred only when endotoxin was administered at the same time or within a few days after antigen administration, but a depressed antibody response occurred if endotoxin preceded antigen. Thus, these early investigations demonstrated the dual nature of the effect of endotoxin on the immune response.
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References
Allison, A. C., and Davies, A.J. S., 1971, Requirement of thymus-dependent lymphocytes for potentiation by adjuvants of antibody formation, Nature (London) 233:330.
Andersson, B., and Blomgren, H., 1971, Evidence for thymus-independent humoral antibody production in mice against polyvinylpyrrolidone and E. coli lipopolysaccharide, Cell. Immuno. 2:411.
Andersson, J., Möller, G., and Sjöberg, O., 1972a, Selective induction of DNA synthesis in T and B lymphocytes, Cell. Immunol. 4:381.
Andersson, J., Sjöberg, O., and Möller, G., 1972b, Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides, Eur. J. Immunol. 2:349.
Andersson, J., Melchers, F., Galanos, C., and Lüderitz, O., 1973, The mitogenic effect of lipopolysaccharide on bone marrow derived mouse lymphocytes: Lipid A as the mitogenic part of the molecule, J. Exp. Med. 137:943.
Armerding, D., and Katz, D. H., 1974, Activation of T and B lymphocytes in vitro. I. Regulatory influence of bacterial lipopolysaccharide (LPS) on specific T-cell helper function, J. Exp. Med. 139:24.
Betz, S. J., and Morrison, D. C., 1977, Chemical and biological properties of a protein rich fraction of bacterial lipopolysaccharides. I. The in vitro murine lymphocyte response, J. Immunol. 119:1475.
Brooke, M. S., 1965, Conversion of immunological paralysis to immunity by endotoxin, Nature (London) 206:635.
Chiller, J. M., and Weigle, W. O., 1973, Termination of tolerance to human gamma globulin in mice by antigen and bacterial lipopolysaccharide (endotoxin), J. Exp. Med. 137:740.
Claman, H. N., 1963, Tolerance to a protein antigen in adult mice and the effect of nonspecific factors, J. Immunol. 91:833.
Coutinho, A., 1975, The theory of the ‘one nonspecific signal’ model for B cell activation, Transplant. Rev. 23:49.
Coutinho, A., Gronowicz, E., Bullock, W. W., and Möller, G., 1974, Mechanism of thymus independent immunocyte triggering: Mitogenic activation of B cells results in specific immune responses, J. Exp. Med. 139:74.
Dresser, D. W., 1961, Effectiveness of lipid and lipidophilic subtances as adjuvants, Nature (London) 191:1169.
Franzi, R. E., and McMaster, P. D., 1968, The primary immune response in mice. I. The enhancement and suppression of hemolysin production by a bacterial endotoxin, J. Exp. Med. 127:1087.
Galanos, C., Lüderitz, O., Rietschel, E. T., and Westphal, O., 1977, Newer aspects of the chemistry and biology of bacterial lipopolysaccharides, with special reference to their lipid A component, in: Biochemistry of Lipids II (T. W. Goodwin, ed.), International Review of Biochemistry, Vol. 14, pp. 239–335, University Park Press, Baltimore.
Gery, I., Kruger, J., and Spiesel, S. Z., 1972, Stimulation of B-lymphocytes by endotoxin: Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T6T6 thymus grafts, J. Immunol. 108:1088.
Golub, E. S., and Weigle, W. O., 1967, Studies on the induction of immunologic unresponsiveness. I. Effects of endotoxin and phytohemagglutinin, J. Immunol. 98:1241.
Goodman, G. W., and Sultzer, B. M., 1977, Mild alkaline hydrolysis of lipopolysaccharide endotoxin enhances its mitogenicity for murine B cells, Infect. Immun. 17:205.
Hamaoka, T., and Katz, D. H., 1973, Cellular site of action of various adjuvants in antibody responses to hapten-carrier conjugates, J. Immunol. 111:1554.
Hoffmann, M. K., Weiss, O., Koenig, S., Hirst, J. A., and Oettgen, H. F., 1975, Suppression and enhancement of the T cell-dependent production of antibody to SRBC in vitro by bacterial lipopolysaccharide, J. Immunol. 114:738.
Hoffmann, M. K., Galanos, C., Koenig, S., and Oettgen, H. F., 1977, B-Cell activation by lipopolysaccharide: Distinct pathways for induction of mitosis and antibody production, J. Exp. Med. 146:1640.
Jacobs, D. M., 1975, Structural and genetic basis of the in vivo immune response to TNP-LPS, J. Immunol. 115:988.
Jacobs, D. M., 1979, Synergy between T cell-replacing factor and bacterial lipopolysaccharide (LPS) in the primary antibody response in vitro: A model for lipopoly-saccaride adjuvant action, J. Immunol. 122:1421.
Jacobs, D. M., 1982, Lipopolysaccharide and the immune response, in: Pharmacology of the Reticuloendothelial System (D. Webb, ed.), pp. 231–251. Dekker, New York.
Jacobs, D. M., and Morrison, D. C., 1975a, Stimulation of T-independent primary anti-hapten response in vitro by TNP-lipopolysaccharide (TNP-LPS), J. Immunol. 114:360.
Jacobs, D. M., and Morrison, D. C., 1975b, Dissociation between mitogenicity and immu-nogenicity of TNP-lipopolysaccharide (TNP-LPS), a T-independent antigen, J. Exp. Med. 141:1453.
Jacobs, D. M., and Morrison, D. C., 1977, Inhibition of the mitogenic response to lipopolysaccharide (LPS) in mouse spleen cells by polymyxin B, J. Immunol. 118:21.
Johnson, A. G., Gaines, S., and Landy, M., 1956, Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide, J. Exp. Med. 103:225.
Kind, P., and Johnson, A. G., 1959, Studies on adjuvant action of bacterial toxins on antibody formation. I. Time limitation of enhancing effect and restoration of antibody formation in X-irradiated rabbits, J. Immunol. 82:415.
Kiyono, H., McGhee, J. R., Wannemuehler, M. J., and Michalek, S. M., 1982, Lack of oral tolerance in C3H/HeJ mice, J. Exp. Med. 155:605.
Louis, J. A., Chiller, J. M., and Weigle, W. O., 1973, The ability of bacterial lipopolysaccharide to modulate the induction of unresponsiveness to a state of immunity, J. Exp. Med. 138:1481.
McGhee, J. R., Farrar, J. J., Michalek, S. M., Mergenhagen, S. E., and Rosenstreich, D. L., 1979a, Cellular requirements for lipopolysaccharide adjuvanticity: A role for both T lymphocytes and macrophages for in vitro responses to particulate antigens, J. Exp. Med. 149:793.
McGhee, J. R., Michalek, S. M., Moore, R. N., Mergenhagen, S. E., and Rosenstreich, D. L., 1979b, Genetic control of in vivo sensitivity to lipopolysaccharide: Evidence for condominant inheritance, J. Immunol. 122:2052.
McGhee, J. R., Kiyono, H., Michalek, S. M., Babb, J. L., Rosenstreich, D. L., and Mergenhagen, S. E., 1980, Lipopolysaccharide (LPS) regulation of the immune response: T lymphocytes from normal mice suppress mitogenic and immunogenic responses to LPS, J. Immunol. 124:1603.
McGhee, J. R., Michalek, S. M., Kiyono, H., Babb, J. L., Clark, M. P., and Mosteller, L. M., 1982, LPS regulation of the IgG immune response, in: Mucosal Immunity (W. Strober, L. A. Hanson, and K. Sell, eds.), pp. 57–72, Raven Press, New York.
Möller, G., 1975, One nonspecific signal triggers lymphocytes, Transplant. Rev. 23:126.
Möller, G., and Michael, G., 1971, Frequency of antigen-sensitive cells to thymus-independent antigens, Cell. Immunol. 2:309.
Morrison, D. C., and Jacobs, D. M., 1976, Binding of polymyxin B to lipid A portion of bacterial lipopolysaccharides Immunochemistry 13:813.
Morrison, D. C., and Ryan, J. L., 1979, Bacterial endotoxins and host immune responses, Adv. Immunol. 28:293.
Morrison, D. C., and Ulevitch, R. J., 1978, The effects of bacterial endotoxins on host mediation systems, Am. J. Pathol. 93:527.
Morrison, D. C., Betz, S. J., and Jacobs, D. M., 1976, Isolation of a lipid A bound polypeptide responsible for “LPS initiated” mitogenesis of C3H/HeJ spleen cells, J. Exp. Med. 144:840.
Mosier, D. E., Mond, J. J., and Goldings, E. A., 1977, The ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an X-linked B cell defect, J. Immunol. 119:1874.
Neter, E., Westphal, O., Lüderitz, O., Gorzynski, E. A., and Eichenberger, E., 1955, Studies of enterobacterial lipopolysaccharides: Effects of heat and chemicals on erythrocyte-modifying, antigenic, toxic and pyrogenic properties, J. Immunol. 76:377.
Neter, E., Gorzynski, E. A., Westphal, O., and Lüderitz, O., 1958, The effects of antibiotics on enterobacterial lipopolysaccharides (endotoxins), hemagglutination and hemolysis, J. Immunol. 80:66.
Newburger, P. E., Hamaoka, T., and Katz, D. H., 1974, Potentiation of helper T cell function in IgE antibody responses by bacterial lipopolysaccharide (LPS), J. Immunol. 113:824.
Parks, D. E., Doyle, M. V., and Weigle, W. O., 1977, Effect of lipopolysaccharide on im-munogenicity and tolerogenicity of HGG in C57BL/6J nude mice: Evidence for a possible B cell deficiency, J. Immunol. 119:1923.
Persson, U., 1977, Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen, J. Immunol. 118:789.
Rifkind, D., 1967, Prevention by polymyxin B of endotoxin lethality in mice, J. Bacteriol. 93:1463.
Rifkind, D., and Palmer, J. D., 1966, Neutralization of endotoxin toxicity in chicken embryos by antibiotics, J. Bacterwl. 92:815.
Rosenspire, A. J., and Jacobs, D. M., 1981, A general interactive model for B cell activation. II. Experimental verification, Cell Biophys. 3:89.
Rosenspire, A. J., Rosen, R., and Jacobs, D. M., 1981, A general interactive model for B cell activation. I. The theory, Cell Biophys. 3:71.
Rosenstreich, D. L., and Mizel, S. B., 1978, The participation of macrophages and macrophage cell lines in the activation of T lymphocytes by mitogens, Immunol. Rev. 40: 102.
Schmidtke, J. R., and Dixon, F. J., 1972, Immune response to hapten coupled to a nonimmunogenic carrier: Influence of lipopolysaccharide, J. Exp. Med. 136:392.
Scott, D. W., Vcnkataraman, W., and Jandinski, J. J., 1979, Multiple pathways of B lymphocyte tolerance, Immunol. Rev. 43:241.
Sjöberg, O., Andersson, J., and Möller, G., 1972, Lipopolysaccharide can substitute for helper cells in the antibody response in vitro, Eur. J. Immunol. 2:326.
Skelly, R. R., Munkenbeck, P., and Morrison, D. C., 1979, Stimulation of T-independent antibody responses by hapten-lipopolysaccharides without repeating polymeric structure, Infect. Immun. 23:287.
Skidmore, B. J., Morrison, D. C., Chiller, J. M., and Weigle, W. O., 1975, Immunological properties of bacterial lipopolysaccharide (LPS). II. The unresponsiveness of C3H/HeJ mouse spleen cells to LPS-induced mitogenesis is dependent on the method used to extract LPS, J. Exp. Med. 142:1488.
Smith, E., and Hammarström, L., 1976, Inhibition of the mitogenicity of the carrier molecule results in loss of immunogenicity of a hapten-LPS conjugate, Acta Path. Microbiol. Scand. Sect. C 84:495.
Spitznagel, J. K., and Allison, A. C., 1970, Mode of action of adjuvants: Effects on antibody responses to macrophage associated bovine serum albumin, J. Immunol. 104: 128.
Sultzer, B. M., 1968, Genetic control of leucocyte responses to endotoxin, Nature (London) 219:1253.
Sultzer, B. M., and Goodman, G. W., 1976, Endotoxin protein: A B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes, J. Exp. Med. 144:821.
Sultzer, B. M., and Nilsson, B. S., 1972, PPD-tuberculin—A B cell mitogen, Nature New Biol. 240:198.
Uchiyama, T., and Jacobs, D. M., 1978a, Modulation of immune response by bacterial lipopolysaccharide (LPS): Multifocal effects of LPS-induced suppression of the primary antibody response to a T-dependent antigen, J. Immunol. 121:2340.
Uchiyama, T., and Jacobs, D. M., 1978b, Modulation of immune response by bacterial lipopolysaccharide (LPS): Cellular basis of stimulatory and inhibitory effects of LPS on the in vitro IgM antibody response to a T-dependent antigen, J. Immunol. 121: 2347.
Unanue, E. R., Askonas, B. A., and Allison, A. C., 1969, A role for macrophages in the stimulation of immune responses by adjuvants, J. Immunol. 103:71.
Von Eschen, K. B., and Rudbach, J. A., 1974, Immunological responses of mice to native protoplasmic polysaccharide and lipopolysaccharide: Functional separation of the two signals required to stimulate a secondary antibody response, J. Exp. Med. 140: 1604.
Von Eschen, K. B., and Rudbach, J. A., 1976, Antibody responses of mice to alkaline detoxified lipopolysaccharide, J. Immunol. 116:8.
Walker, S. M., and Weigle, W. O., 1978, Effect of bacterial lipopolysaccharide on the in vitro secondary antibody response in mice. I. Description of the suppressive capacity of lipopolysaccharide, Cell. Immunol. 36:170.
Watson, J., Riblet, R., and Taylor, B. A., 1977, The response of recombinant inbred strains of mice to bacterial lipopolysaccharide, J. Immunol. 118:2088.
Watson, J., Kelley, K., Largen, M., and Taylor, B. A., 1978, The genetic mapping of a defective LPS response gene in C3H/HeJ mice, J. Immunol. 120:422.
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© 1983 Plenum Press, New York
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Jacobs, D.M. (1983). Immunomodulatory Effects of Endotoxin. In: Nowotny, A. (eds) Beneficial Effects of Endotoxins. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4364-6_16
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DOI: https://doi.org/10.1007/978-1-4684-4364-6_16
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