To investigate the defensive roles and production of interferon and antibodies, C3H/He mice were subjected to various immunosuppressive treatments and infected with influenza virus. In infected normal control mice the pattern of pulmonary viral growth can be divided into three phases. The first phase is characterized by an exponential increase of virus titer, the second by a rapid decrease, and the third by a moderate decrease. At the time of transition from the first phase to the second in pulmonary virus growth, interferon could be detected in the tracheobronchial washings of infected mice, but neutralizing antibodies could not. In infected B cell-deprived mice and infected anti-µ-treated mice, the transition from the first phase to the second occurred without any detectable antibody production, and interferon could be induced in the early stage of infection. However, the pulmonary virus in these mice increased again exponentially until the death of the mice. In infected T cell-deprived mice which could not induce interferon, but produced IgM-neutralizing antibodies, the second phase was not observed after the first phase, but a transient plateau phase could be demonstrated, and then the pulmonary virus increased again exponentially until the death of the mice. In anti-γ-treated infected mice, pulmonary virus growth and production of interferon and neutralizing antibody were almost similar to those of infected normal control mice except for the absence of IgG neutralizing antibody production. Although anti-α-treated infected mice produced interferon and no IgA antibody, the transition from the first exponential increase of pulmonary virus to the second rapid decrease was seen, but then the virus increased exponentially again until the death of the mice. These results suggest that interferon plays an important role in the transition from the first phase to the second, and that T cells are required for interferon induction in mice infected with influenza virus. These data also suggest that IgA antibodies play an important role in the inhibition of virus propagation in the lungs after the disappearance of interferon. Moreover, infected T cell-deprived mice could produce only IgM neutralizing antibodies, but not IgG and IgA antibodies. Therefore, T cells are required for the production of IgG and IgA antibodies and eventually for defense functions in mice infected primarily with influenza virus.
Antibodies to influenza virus have been shown to be present not only in serum, but also in secretions of the respiratory tract (1–4). Gamma A is the predominant immunoglobulin class in the secretions, whereas this immunoglobulin is a minor component in the serum. The γ A of the secretions differs chemically and antigenically from serum γ A. These observations suggest that antibodies associated with secretory γ A are produced locally, and are not simply the result of transudation from the serum. There is considerable indirect evidence for the synthesis of local antibodies in the respiratory tract. The problem remains to elucidate the mechanism of local antibody formation. The lymphocytosis-promoting factor (LPF) obtained from Bordetella pertussis has been shown partially to suppress the formation of circulating antibody when given intravenously in mice (5). Therefore, the possibility of demonstrating a dissociation between the levels of antibody activity in the serum and in the secretions of mice infected with influenza virus was investigated.
The study on a virus lysing halophilic bacteria is very interesting, as the synthesis of protein and nucleic acid at high salt concentration may be rather easily investigated.The halophilic bacterium we used is Bacillus circulans var. Yamada 107 strain, which grows optimally in the nutrient broth containing 5 / NaCI and can grow considerably well even in the medium containing 10% NaCI. Onishistrain of its bacteriophage was originally isolated from the soil obtained near our Institute.Pure culture of this strain was secured by six serial cultivations from isolated plaque on agar plates. A high titer phage stock solution (ca. 5 x 1010 phages/ml) was produced by means of the ordinary method. In the following experiments, the final concentration of mixed bacteria and phages were always ca. 5 x 108/ml, respectively. 1) Rate of adsorption One ml of 18 hours' bacterial culture containing 5 % NaCI (ca. 5 x 108 cells/ml) was added to each 9 ml of nutrient broth containing 3, 5, and 7 % NaCI respectively, and grown to a concentration of ca. 5 x 108 cells/ml at 37°C with aeration.Appropriate amounts of phage were added to this bacterial culture and the rate of adsorption was determined at known time intervals.
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