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Ribonucleic acid in the immune response

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Summary

In the studies of experimental salmonellosis, immunization of mice with a live vaccine SER ofS. enteritidis was found to be effective against further infection with virulentS. enteritidis 116-54. Macrophages obtained from the peritoneal cavity, subcutaneous tissue or liver of immunized mice inhibited intracellular growth of bacteria and resisted cell degeneration caused by engulfment of virulent 116-54 bacteria. This immunity was called cellular immunity.

We discovered by chance in 1961 a transfer agent of immunity (TA) from the culture fluid of immunized macrophages. This agent is RNA in nature and can be extracted from the spleen, peritoneal exudate cells or the lymph node of immunized animals and is called immune (i) RNA. We could demonstrate antibody activity in macrophages treatedin vitro orin vivo withiRNA by the immune adherence hemagglutination technique.

Cellular immunity against tumor cells could be transferredin vitro orin vivo to lymphocytes throughiRNA prepared from the spleen cells of syngeneic, allogeneic and xenogeneic animals immunized with the tumor cells.

We prepared iRNA against antigens capable of inducing humoral antibody production in animals, i.e., RBCs, bacterial toxin, bacterial flagella and hapten-protein conjugates. Serum antibody was not demonstrated in recipient animals ofiRNAs by single or repeated injections of these agents. However, in these animals an increase in the number of specific antibody-carrying cells was found as rosette-formers. It was found further that prior injection ofiRNA could induce immunologic memory and produced a high titer of humoral antibody after a boosting stimulation with a small dose of the corresponding antigen. The required interval between the firstiRNA and the second antigenic stimulation, and the minimal effective doses of iRNA and antigen are described.

We studied the interaction ofiRNA with either T- or B-cells and with both cells using adoptive transfer system, athymic nude mice and neonatally thymectomized (NT) mice. Immune RNAs against T-dependent and T-independent antigens could not induce the proliferation of antibody-carrying cells in cyclophosphamide-treated (B-cell depleted) mice. But these agents could induce the proliferation of rosette-formers, implying thatiRNAs can replace some role of T-cells even against T-dependent antigens. B-cells can be directly activated by treatment withiRNA against both T-dependent and T-independent antigens, and they differentiated into rosette-formers.

Passive transfers ofiRNA were successful in establishing immunity against infection withS. enteritidis, or immunity toSalmonella flagella, RBCs and hapten-protein conjugates. The ability ofiRNA to confer a secondary response of antibody formation is serially and passively transmissible in recipient animals. These facts suggest the presence of some mechanism that is responsible for the amplification of antigenic stimulation in the immune response. The RNA-dependent RNA polymerase and RNA-dependent DNA polymerase are presented and their role in the immune response is discussed.

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Authors and Affiliations

  1. Department of Microbiology, School of Medicine, Gunma University, Maebashi, Japan

    Susumu Mitsuhashi, Satonori Kurashige & Nobuo Yamaguchi

  2. Department of Oral Bacteriology, Nippon Dental University, Migata, Japan

    Kazuko Saito

Authors
  1. Susumu Mitsuhashi

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  2. Kazuko Saito

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  3. Satonori Kurashige

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  4. Nobuo Yamaguchi

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