Benjamin V. Siegel

Serum Agglutinin Levels to Sheep Red Blood Cells in Mice Infected With Rauscher Virus.

Summary Primary agglutinin liters were depressed in mice immunized with sheep red blood cells 8 days or more following inoculation of l0-1 or 10-2 dilutions of Rauscher leukemogenic virus. The extent of depression was proportional to virus dose and could frequently be detected before the appearance of hematological evidence of leukemic development. Immunization 7 days before, at the time of, or 4 days after, viral inoculation did not result in depression of primary titers. In all these instances a lag was noted in antibody response 4 days after the secondary stimulus; however, by 7 or 8 days increases in antibody titers over primary levels were similar in both virus and control groups. Even in mice markedly leukemic at the time of secondary challenge no depression of the secondary response was observed. A possible mechanism concerning the influence of viral leukemogenesis on the immune response is discussed.

Ascorbic Acid and the Immune Response

Since the introduction of ascorbic acid as an antiviral and antibacterial agent (Klenner, 1951; McCormick, 1952; Klenner, 1974) interest has focused on the possible immunologic mechanisms involved in its protective effect. The role of ascorbic acid in the immune response is reviewed here with regard to cellular and humoral functions, and experiments pertaining to the role of ascorbic acid in autoimmunity and anaphylaxis are discussed.

Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells.

Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 x 106 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.

TUMOR VIRUS EFFECTS ON IMMUNOCYTE PRECURSOR CELLS. HEMOPOIETIC STEM CELL BEHAVIOR AND LEUKEMOGENIC SUSCEPTIBILITY

Studies of Rauscher virus-induced erythroleukemia have demonstrated immunodepressive effects in the host and enhanced leukemogenesis with adjuvant administration. These observations led to the study of leukemic development in the NZB strain as a natural model of the experimentally adjuvant-stimulated animal. The results of such investigation would attribute the increased susceptibility of NZB mice to the possession of an enlarged population of pluripotent hemopoietic stem cells in active cell cycle. Studies with radiation chimeras have further shown that elevated endogenous spleen colony formation, the increased potential for autoimmunity, and for susceptibility to Rauscher viral leukemogenesis are all linked through the NZB hemopoietic system. It is concluded that the presence of an enlarged compartment of cyclically active stem cells may be an etiologic factor in the susceptibility to both virus-induced leukemia and the development of autoimmune disease.

Observations on deuterium treatment of a virus-induced mouse leukemia

Abstract The effects of deuterium administered as drinking water on a virus-induced mouse leukemia were studied. Generally, the earlier the initiation of deuterium administration following tumor virus inoculation the higher was the percentage of survivors. There also appeared to be a dosage factor in that 30 per cent deuterium oxide provided greater beneficial results than a concentration of 15 per cent.

The Reticuloendothelial System and Tissue Injury

The present topic “The Reticuloendothelial System and Tissue Injury” seems rather too broad and inclusive, since the system recognizably encompasses heterogeneous cells widely scattered throughout the body, providing a variety of functions protective as well as injurious. Tissue injury may result from direct cell-cell contact between sensitized lymphocytes and target cells, or more frequently, may arise secondary to the induction of an inflammatory reaction. Mediators elaborated as a consequence of the immune response bring about a localized accumulation of neutrophils, monocytes, lymphocytes, and plasma constituents which are intimately associated with the tissue damage. The role of the RES in tissue injury thus includes a variegated spectrum of cellular involvement and immune reactions both antibody- and cell-mediated. These are addressed by a number of chapters in this volume. We shall therefore limit this presentation to a brief review of a few of the etiological factors and mechanisms involved in the mediation of tissue injury by the RES.

Immune response to sheep erythrocytes with cytoxan and hybaroxia

Abstract Concurrent administration of 97% oxygen at 3.4 atmospheres absolute pressure for 30 minute periods twice daily, five days per week, was without significant effect in potentiating immunosuppression to sheep erythrocytes by single doses of 40 mg/kg and 80 mg/kg body weight of cytoxan. Possible HPO potentiating effects with other antigen-immunosuppressive systems are not excluded, and such studies are presently in progress.

Influence of Deuteration on Circulating Antibody Levels in the Mouse.

Summary Depressed serum antibody levels were observed in mice drinking 30% D2O continuously, starting 17 days before immunization with BSA in complete Freunds adjuvant. Adjuvant-induced increases in body weight were also diminished in these animals. Ten days pretreatment with heavy water did not, however, alter the response to BSA. In another group of mice pretreated with heavy water for 7 days, primary agglutinin levels to sheep red cells were normal in the continuously deuterated mice for the first 2 weeks following immunization, diminishing thereafter. The extent of heavy water pretreatment required suggests that mere equilibration of body fluids and exchangeable tissue hydrogens with 30% D2O does not result in depressed antibody levels. Only after substantial deuterium was incorporated by synthesis into non-exchangeable sites were circulating antibody titers observed to be diminished.

T-Cell-Mediated Injury

Despite numerous studies performed during the last decade, the actual mechanism of cell-mediated injury is still poorly understood. However, on the basis of in vitro findings, a variety of pathways have been proposed whereby different categories of immunocytes, in concert with macrophages, antibodies, and soluble mediators (lymphokines), participate in tissue and cellular damage. Different effector cell types, including T lymphocytes, B lymphocytes, macrophages, and polymorphonuclear leukocytes, have been implicated. We shall discuss here the mechanism of activation and lytic activity of T lymphocytes, a possible role for oxidative metabolism in T-lymphocyte function, and alterations of T-lymphocyte function in autoimmune diseases.

Antibody-Mediated Immunodepression in New Zealand Black Mice

Summary Passive administration of hyperimmune antiserum into syngenic NZB recipients produced a marked depression of spleen anti-SRBC plaque formation. This antiserum was equally effective in BALB/c mice, depression persisting in both strains for as long as 2 months following ip injection of 0.02 ml serum. These observations would suggest that the immunological hyperresponsiveness previously described for NZB strain mice does not derive from a deficiency in 7S antibody-mediated feedback inhibition of the immune response. Transfer of serum from 1-year-old Coombs positive mice and from 7-month-old ANA-positive animals into preautoimmune baby NZB recipients was without effect on the subsequent course of development of antinuclear antibody and of Coombs reactivity. The inability to alter the course of autoantibody formation by such passive transfer of sera may involve a number of factors which are discussed.