The mice which had been immunized with highly virulent live S. enteritidis acquired a strong immunity against the bacilli and could perfectly survive a challenge with intravenous injection of a highly virulent strain S. enteritidis 116-54 in a dose of 1, 000×MLD. The sera of the mice contained O and H antibodies but no demonstrable factor to prevent death due to infection. However, large mononuclear cells from liver, subcutaneous tissue and peritoneal cavity of the immunized mice exhibited an immune activity. The cells could suppress intracellular proliferation of phagocytized highly virulent bacilli and finally digested them without addition of exogenous immune sera. The activity was regarded as an expression of cellular immunity. It could be established only after contact with live bacilli. The supernatant fluid of the culture of the immunized cells or the cellular fraction which was sedimented at 100, 000g contained a transfer agent which could transfer cellular immunity. The transfer agent was inactivated by RNase but resisted DNase or trypsin treatment. An antibody reacting to live S. enteritidis 116-54 was demonstrated in the immunized cells, even after absorption with formalin treated bacilli which contained O and H antigens. This antibody, defined as the cellular antibody, could suppress the growth of S. enteritidis 116-54 in vitro in collaboration with complement and lysozyme.
In the present experiments we have investigated the effect of ovariectomy and/or thyroidectomy upon the death rate in rats poisoned with carbon tetrachloride. It was found that the death rate of the ovariectomized rats was lower than that in non-spayed animals. Thyroidectomy also produced a significant decrease in the death rate of the carbon tetrachloride-treated animals. Almost the same results were obtained by thyroidectomy plus ovariectomy. These findings may be explained by assuming that the extirpation of the ovaries and/or the thyroid lessens overburden of the intoxicated liver.
Pregnant mice were infected with the PR8 strain of influenza A virus and the possible penetration of the virus through the placenta and the possible growth of virus in the embyro were examined. 1) By using 32P labeled virus, quick and easy penetration of the virus through the placenta was proved. In this study, the virus was given to pregnant mice by intravenous injection. As a result significant accumulation of radioactivity was found in the embryo. 2) Pregnant mice were infected by inhalation of the virus mist, and the growth of virus both in maternal lung and embryonal tissues were pursued. Embryonal lung and brain allowed a good growth of virus. The growth in the placenta was also proved but its maximum was found rather at the late stage of infection. Almost the same results were obtained both with fluorescent antibody and in histopathological studies. 3) Pregnant mice were infected with a small amount of inoculum by means of inhalation, and its effects on the progress of pregnancy and on the growth of embryo were investigated. When the pregnant mice were sacrificed before delivery, a significant increase in number of absorbed fetuses was found. Moreover, the rate of stillbirth was increased and the survival rate of newborns delivered from infected mothers was decreased.
The cells, which were cultivated from the omentum of BAS-sensitized rabbits and grown in our special culture medium, contained antibodies to BSA, as detected by immunohistochemical and immunochemical methods. When the antigen (BSA) was introduced into the culture, the cells showed momentarily characteristic morphologic changes suggesting a decreased activity of cell membrane. The antibodies in the cells seemed to be due to 19S antibodies, because the morphologic changes in the cells, passively sensitized with 19S antibodies, were undoubtedly indistinguishable from those in the above actively sensitized cells. On the other hand, the cells, passively sensitized with 7S antibodies, showed momentarily different morphologic changes suggesting an increased activity of the cell membrane. These observations possibly indicate an important relationship between the chemical structure and biologic action of these two antibodies to BSA. At present, we call the cells ‘omentum cell’; and they may by very useful in the study of the formation and function of antibodies.
The purpose of this paper is to determine what kind of cell is involved in antibody production in the delayed type of hypersensitivity and to clarify the mechanism by which the cells participate in the process. Attempts to solve these problems have been made in four ways: 1) Passive transfer of delayed type of hypersensitivity with lymphocytes, neutrophils and peritoneal exudate cells (living and disrupted), 2) tests for neutralization of tuberculin by lymphocytes (living and disrupted), 3) attempted breakdown of acquired and native im-munological tolerance to tuberculin with lymphocytes (living and disrupted), and 4) development of tuberculin hypersensitivity in thymectomized rabbits. All results of these experiments suggest that lymphocytes are responsible for the exhibition of hypersensitivity. Reviewing my own and other author's data, a new conception is presented which copes with the mechanism of the passive transfer of hypersensitivity as well as with the breakdown of immunological tolerance by living or disrupted lymphocytes. The core of the conception is that the recipient's own immunologically competent cells are also involved in the development of hypersensitivity, receiving some information from living lymphocytes or lymphocyte fragments transferred.
In the present report, I attempted to identify the nature of humoral and cellular factors in heterotransplantation immunity, assuming that the former would confer on the animals transplantation immunity by passive immunization with serum, while the latter would be adoptively transferred to recipients with sensitized cells. A group of mice was inoculated with rat ascites hepatoma cells. Eighteen to 23 days after the transplantation, the serum and nucleated cells were collected from the peritoneal fluid, spleen and mesenteric lymph node were pooled separate-ly. Then, the extraction of effective substances was performed by treatment of the specimens with sonic oscillation, salting out with ammonium sulfate, Sephadex column chromatography, sucrose density gradient centrifugation, etc. 1. The active factor in immune sera was found to be 7S IgG, whereas no high molecular immunoglobulin effective in accelerating the rejection of target cells could be found. 2. Passive transfer of transplantation immunity was accomplished with a soluble extract from sensitized cells. The active agent was specific for the sensitizing cells and behaved like a 19S IgM in demonstrating a sensitivity to 2-mercaptoethanol. 3. Judging from the results of experiments employing a temporary deprivation of complement as well as blockade of peritoneal phagocytes, cooperation of complement and phagocytic cells seemed to be necessary for the full activity of the immune serum against the graft. 4. On the contrary, the sensitized cell sonicate exerted its effectiveness in co-operation with complement and non-phagocytic cells, probably lymphoid cells, of recipient mice.
The distribution rate of sodium iodide (Na131I) and toxohormone labeled with Na131I in rats under various experimental conditions was described. Toxohormone extracted from the cancer tissue of the stomach removed by surgical operation exhibited a remarkable inhibitory effect on liver catalase. Compared with the distribution of Na131I in the liver and spleen of the normal rats, that of Na131I labeled toxohormone in the above organs was found to be characteristically decreased. It was also decreased in the liver of splenectomized rats. The distribution of Na131I was reduced in the liver and spleen of rats, which had been treated with toxohormone for successive two days. It was also decreased in the above organs of rats with moderate liver impairment. The function of the reticuloendothelial system in the liver and spleen of the tumor bearing organisms was regarded to be important in the inactivation of toxohormone released from tumor tissue. The distribution rate of labeled toxohormone in the alimentary canal, especially in the stomach, was found to be increased after intraperitoneal administration of the substance. The results were interpreted in association with the excretion of Na131I labeled toxohormone from the alimentary canal.
Kininase activity in venous blood has been studied in 17 healthy persons, 15 patients with hyperthyroidism, 12 with liver diseases and 57 with other diseases. The activity of this enzyme was expressed by the destruction rate of synthetic bradykinin during the incubation with venous blood. The estimated values were 53-72% (mean 64.4±4.93%) in healthy persons. Patients with hyperthyroidism and patients with liver diseases showed markedly higher activity than normal levels. No significant changes in the activity were seen in other diseases.
Alkaline phosphatase activity of neutrophils was estimated histochemically with special reference to various types of hemolytic disorders. Enzyme activity tended to be lower than normal in all but one of the cases studied. Leukocytes incubated for one hour at 37°C in plasma obtained from a patient with paroxysmal nocturnal hemoglobinuria and from a patient with congenital spherocytosis showed a decrease in enzyme activity. When leukocytes were incubated in normal plasma containing bovine hemoglobin, enzyme activity also decreased. Plasma obtained from patients with hyperbilirubinemia caused by bile duct obstruction did not affect enzyme activity in vitro at all. It was concluded from these observations that the low enzyme activity seen in various hemolytic disorders was due to the inhibitory effect of hemoglobin in plasma and not due to indirect bilirubin. Differences in enzyme activity in these hemolytic states were considered to be due to differences in plasma hemoglobin concentration.