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Biomedical subjects

N Gengozian

Publications and source records attributed to N Gengozian.

At least 37 records · Page 2Linked to original sources

Subnormal expression of cell-mediated and humoral immune responses in progeny disposed toward a high incidence of tumors after in utero exposure to benzo[a]pyrene.

Pregnant mice were exposed to 150 micrograms benzo[a]pyrene (BaP) per gram of body weight during fetogenesis (d 11-17 of gestation) and the progeny were assayed for humoral and cell mediated immune responses at different time intervals after birth. Immature offspring (1-4 wk) were severely suppressed in their ability to produce antibody-(plaque-) forming cells (PFC) against sheep red blood cells (SRBC) and in the ability of their lymphocytes to undergo a mixed lymphocyte response (MLR). Lymphocytes from these progeny showed a moderate to weak capacity to inhabit production of colony-forming units (CFU) in host spleens following transfer with semiallogeneic bone marrow (BM) cells into lethally X-irradiated recipients syngeneic to the BM (in vivo graft-versus-host response, GVHR). A severe and sustained suppression in the MLR and the PFC response occurred from the fifth month up to 18 mo. The in vivo GVHR, also subnormal later in life, was not as severely suppressed as the other two parameters. Tumor incidence in the BP-exposed progeny was 8- to 10-fold higher than in those encountering corn oil alone from 18 to 24 mo of age. These data show that in utero exposure to the chemical carcinogen BaP alters development of components needed for establishing competent humoral and cell-mediated functions of the immune apparatus and leads to severe and sustained postnatal suppression of the defense mechanism. The immunodeficiency exhibited, particularly in the T-cell compartment (MLR, GVHR), before and during the increase in tumor frequency, may provide a favorable environment for the growth of nascent neoplasms induced by BaP.

Animals↗

Antibody formation by one or both lymphoid populations present in chimeric marmosets.

Development of an isoimmune serum capable of identifying a specific leukocyte antigen in the marmoset, Saguinus fuscicollis illigeri, permitted detection of lymphoid cell chimerism in this species by the cytotoxic test. This reagent was then used to identify the cell population in the chimera responsible for antibody production against a test antigen, sheep red blood cells. Primary in vitro antibody formation as measured by plaque-forming cells with blood leukocytes or splenic lymphocytes of six animals chimeric for the leukocyte antigen, MLA-1, revealed an immune response by both cell types of the chimeric population from three animals and a response by only one cell type in the other three.

Animals↗

Antibody-dependent cellular cytotoxicity with platelets as the target cell: potential application to the study of immune thrombocytopenia.

Antibody-dependent cellular cytotoxicity (ADCC) with platelets as the target cell is demonstrated with white blood cells, platelets and anti-platelet antibody obtained from marmosets. Greatest ADCC activity was observed with cell populations enriched for polymorphonuclear (PMN) cells and adherent cells. Non-adherent cells and lymphocytes obtained from blood pretreated with carbonyl iron showed a lower yet significant degree of activity. The virtual absence of PMNs and monocytes from these preparations indicates that a non-phagocytic-mediated destruction of platelets can occur by an ADCC process. Platelets having IgG deposited on them as a consequence of an autoimmune reaction following an interspecies platelet immunization are not necessarily susceptible to lysis by an ADCC mechanism. The ADCC reaction system as described and the results obtained suggest one can monitor platelets, effectors and soluble factors from immune thrombocytopenic patients and animals with respect to this mode of destruction in vivo.

Animals↗

Marmoset response to immunization with porcine zonae pellucidae. Measurement of antibody activity with an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in sera from a marmoset inoculated with porcine zonae. Antibodies which bound to heat solubilized zonae immobilized in microtiter plates were detected by an enzymatic reaction using goat antimarmoset IgG conjugated to alkaline phosphatase. During a nine-week immunization period, the antibody response profile as determined with the ELISA was parallel to that obtained with an indirect immunofluorescent test on intact zonae. This procedure has certain advantages over presently used methods of titrating anti-zona sera.

Animals↗

Antibodies selectively reactive to autologous and host-type platelets are obtained following interspecies immunizations in marmosets.

Interspecies immunization of marmosets with platelets leads to an acute thrombocytopenia which appears to be immunologically mediated. The thrombocytopenia is preceded by the formation of antibodies to the donor platelet antigen and deposition of IgG on the host's platelets. Examination of sera obtained from these animals during the course of the disease has revealed the presence of antibodies towards autologous and host-type platelets. Autologous antibody was found when thrombocytopenia was severe; upon platelet recovery, this antibody was absent or reduced in titre. This in vivo absorption of host-specific (autologous) antibody led to detection in the serum of antibodies reactive to other members of the host species. The presence of such host-type antibodies appeared to be related to the intensity of antigenic stimulation, the amount of antibody formed and the degree of thrombocytopenia. Deposition of IgG on the host's platelets coincided with the appearance of the anti-host antibodies; whether the IgG detected on the host's platelets is exclusively cross-reactive antibody or includes also an immune complex is not yet known. Finally, the data have identified potential immunogenetic differences among members of two marmoset species with respect to platelet antigens.

Acute Disease↗

The effect of low exposure-rate gamma irradiation on T and B lymphocyte function in the mouse.

The effect of chronic irradiation on T and B cell numbers and function was studied in mice. Cobalt 60 gamma radiation at 6 R/hour reduced the numbers of anti-SRBC PFC in the spleen, with minimal levels recorded after total exposures of 1000-2000 R. Recovery was incomplete after 1000 R, reaching only 40-50 per cent of normal in four months and remaining at that level for the animal's lifetime. The long-term deficiency in PFC formation was not due to a quantitative lack of T or B cells since normal cell numbers were observed in the spleen 60-144 days after 1000 R. Adoptive transfer studies with combinations of bone marrow and thymus cells, or of splenic T and B cells, from normal and irradiated mice, revealed functional defects in both cell compartments during the first two months. Normal and near normal function of T and B cells occurred 100 days postirradiation, a time when the splenic in vivo response was still only 50 per cent of the controls. The latter observation suggests that the microenvironment of the chronically irradiated spleen alters factors regulating T and B cell interactions in response to a T-dependent antigen.

Animals↗

Depressed humoral immunity and increased tumor incidence in mice following in utero exposure to benzo[alpha]pyrene.

Exposure of mice to a single small dose of benzo[a]pyrene in utero leads to a severe suppression of the anti-sheep erythrocyte plaque-forming response shortly after birth that persists into later life. There is also an 11- to 13-fold increase in the frequency of tumors in these mice at 56-78 wk of age compared to the untreated control group. Mice exposed to 150-R X-irradiation in utero, after an early immune suppresion, show recovery of the plaque-forming response with no increase in tumor incidence. The sustained suppression in immune status induced in mice by exposure to benzo[a]pyrene during fetal life may be related to an altered immune surveillance mechanism and a consequent increased susceptibility to tumor development.

Animals↗

Presumptive evidence for the absence of functional germ cell chimerism in the marmoset.

Presumptive evidence for functional germ cell chimerism in the marmoset was evaluted by calculating the offspring sex ratio of young derived from animals in which the blood chimerism status was known. In the four possible mating combinations involving chimeric and non-chimeric marmosets, there was no apparent deviation from the anticipated 1:1 sex ratio. Analysis of 2,500 primary spermatocytes from ten known blood chimeras failed to reveal a single cell in which an unequivocal XX bivalent could be identified. The combined breeding and cytogenetic data offer presumptive evidence against functional germ cell chimerism in the marmoset.

Animals↗

Isoimmunizations among marmosets to identify leucocyte antigens.

Saguinus fuscicollis ssp., S.o. oedipus, and S. nigricollis marmosets were immunized with white blood cells (WBC) from S.f. illigeri marmosets. Of the three genetic donor-host combinations attempted, only an interspecies immunization of S.o oedipus marmosets resulted in antibody formation which was detectable by agglutination or cytotoxicity tests. Analysis of one of the antisera with a panel of WBC from S.f. illigeri marmosets indicated varying specificities, reactions ranging from strong, intermediate, to completely negative. That the serum was detecting genotypic as well as phenotypic markers was suggested by the similarity of reactions of WBC from co-twin pairs and in preliminary testing of individual families.

Agglutination Tests↗

Fetal hemoglobin: in vivo stimulation by D-thyroxine in adult marmosets.

Reactivation of fetal hemoglobin gene expressions was studied in new-world monkeys (marmosets). After a series of intraperitoneal injections of D-thyroxine, fetal hemoglobin production was increased in three experimental animals. Control animals were unaffected by the injection of the solvent. Because the percentage of cells containing fetal hemoglobin exceeded the total percentage of fetal hemoglobin, it was concluded that thyroid hormone influenced the synthesis of fetal hemoglobin rather than the development of a population of fetal cells.

Animals↗

The comparative radiosensitivity of T and B lymphocytes.

This study deals with the comparative effects of gamma irradiation on T and B lymphocytes in mice. Quantitatively, splenic T cells appeared substantially more radioresistant than B cells. However, in the thymus, the mesenteric lymph node and peripheral blood, both cell types were highly radiosensitive. No repair processes could be detected with respect to lymphocyte killing, since reducing the dose rate or fractionating the dose resulted in no reduction in cell destruction. Splenic B cells which remained intact 3 days after doses of 600 R or larger were impaired in their ability to form caps, whereas T cells capped normally. Spleen cells which were viable 3 days after irradiation bore latent radiation damage which was manifested as a reduced ability to survive and generate plaque-forming cells in vitro. Attempts to separately assess irradiated T and B cell immunocompetence in vitro suggested that at doses of 300 R and below, surviving B cells were more impaired than T cells. After a 600 R dose, neither cell type appeared to be functional.

Animals↗

Antigenic cross-reactivity between human and marmoset zonase pellucidae, a potential target for immunocontraception.

Cross-reactivity between marmoset, chimpanzee, human and pig zona pellucida antigens was demonstrated by immunofluorescence and zona precipitation. In marmosets, anti-zona antibody prevented sperm attachment to eggs in vitro, and the antibody could be detected on zonae of ovarian oocytes following passive immunization. Use of the marmoset as an animal model in testing feasibility of the zona approach to immunocontraception is discussed.

Animals↗

Marmoset species variation in the humoral antibody response: in vivo and in vitro studies.

A comparison of the in vivo and in vitro antibody response capabilities of two marmoset species, Saguinus fuscicollis and Saguinus oedipus oedipus, revealed the former to be superior in elaborating humoral antibody. In vivo challenges with Escherichia coli lipopolysaccharide (LPS) and Salmonella typhi flagella consistently yielded higher antibody titres in S. fuscicollis; indeed, with LPS antigen, multiple inoculations of S.o. oedipus marmosets led ultimately to a decrease in antibody formation, in contrast to the anamnestic response of S. fuscicollis. This species differential in immune competence was also suggested in the in vitro stimulation of peripheral blood leucocytes (PBL) and spleen cells with sheep red blood cells (RBC). None of 55 S.o. oedipus PBL cultures and 49 of 89 (55%) S. fuscicollis cultures responded to the test antigen. A similar differential in response to sheep RBC was noted with the spleen cells of each species, although this report contrasts the antibody-forming potential of two marmoset species, a comparison of the immunological response profile of marmosets to those of other laboratory animals challenged with similar antigens suggests these primates may be relatively incompetent. The possible relationship between the haemopoietic chimerism of marmosets and a diminished immune competence is discussed.

Animals↗