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D Halperin

Publications and source records attributed to D Halperin.

30 records · Page 2Linked to original sources

Induction by an immunogenic immunomodulating agent of nonspecific T cell suppression of lymphocyte responsiveness in MLR but not of antibody production.

Spleen cells derived from BALB/c mice that had been repeatedly immunized with the methanol extraction residue (MER) fraction of tubercle bacilli exhibited a depressed capacity to act as responder cells in allogeneic and syngeneic mixed lymphocyte reactions (MLR). Previously reported studies revealed that such spleen cells are also defective in the in vitro generation of antibodies. In order to determine the nature of the cells responsible for the depressed MLR reactivity, purified populations of splenic macrophages, B lymphocytes, T lymphocytes originating from normal and from MER-immunized mice, and cell culture supernatants were added to MLR mixtures consisting of normal mouse splenocytes. Macrophages originating from MER-immunized mice and their culture supernatants exerted a significantly higher suppressive effect on MLR than that of corresponding preparations from normal mice. Splenic T cells originating from MER-immunized mice and their supernatants also significantly suppressed the MLR response. However, the same T cell populations that were inhibitory in MLR failed to suppress the in vitro generation of antibodies against sheep red blood cells in the presence of either MER or 2-mercaptoethanol. These and previously reported findings indicate that a nonspecific immunomodulating agent, MER, can, under certain conditions of treatment, elicit the induction of nonspecific suppressor T cells for MLR but not for antibody production, and, accordingly, can inhibit cellular and humoral immunological responsiveness by different mechanisms.

Adjuvants, Immunologic

Effects of the methanol extraction residue (MER) tubercle bacillus fraction on the production of antibodies in vitro. III. Consequence of prior sensitization to MER.

Mice repeatedly immunized with the methanol extraction residue fraction of tubercle bacilli (MER) in incomplete Freund's adjuvant produced high titers of circulating antibodies against MER, as assessed by the enzyme-linked immunosorbent assay (ELISA) method. Spleen cells derived from these animals failed to respond to the usual nonspecific immunopotentiating influence of MER on the primary production of antibodies (generation of specific plaque-forming cells) in vitro to sheep red blood cells. The defect was expressed by B lymphocytes and splenic macrophages, but not by splenic T lymphocytes or peritoneal exudate macrophagic cells. Impaired responsiveness by spleen cells from MER-immunized animals to nonspecific immunostimulation was also expressed with regard to another, unrelated biological response modifier, lipopolysaccharide. There was no impairment of responsiveness to polyclonal mitogenic stimulation. Possible mechanisms of the effects described are discussed.

Adjuvants, Immunologic

Effects of the methanol extract residue (MER) tubercle bacillus fraction on the production of antibodies in vitro. II. Effects on macrophage and lymphocyte populations.

The effect of the methanol extract residue (MER) fraction of BCG tubercle bacilli on the generation of primary antibody responsiveness in vitro to sheep red blood cells (SRBC) was ascertained in cell reconstitution experiments, employing enriched populations of mouse macrophages and of T and B lymphocytes. In each of the antibody generation cultures one or another of the cell fractions had been exposed to MER, either by treatment of the donor animals or by preincubation with the agent for 48 hr in vitro. In some experiments, supernatants of MER-preincubated cells were employed in place of the cells. Macrophages and T cells that had been exposed to MER in vivo or in vitro and their supernatants demonstrated a markedly greater effect than nonexposed cells in the generation of direct specific plaque-forming cells (PFC) upon antigenic stimulation of the cultures with SRBC. In contrast, PFC production was not stimulated in B-lymphocyte populations that had been in contact with the agent.

Adjuvants, Immunologic

Type C virus and immunoglobulin A production by murine myeloma MOPC-315: two independent activities.

The suspected correlation between cessation of type C virus production and halt in immunoglobulin secretion by murine myeloma cells was studied. Employing two variants of the murine myeloma MOPC-315, immunoglobulin A-producing and nonproducing cells, we demonstrated that the two myelomas release similar levels of type C viruses which share common nucleotide sequences and that the viral genomes are equally expressed within the cells. Thus, the suggested relation between these two activities does not apply for MOPC-315 cells and probably for other murine myelomas also.

Animals

Paraquat poisoning in southern Mexico: a report of 25 cases.

Paraquat is a bipyridyl herbicide used world-wide. Although accidental and deliberate ingestions of lethal doses have been reported from many countries, no case has ever been described in Mexico. The authors report on 25 cases of Paraquat poisoning in the state of Chiapas, Mexico, that occurred between 1988 and 1990. Eighty percent of the cases were men, and 64% of the cases died. Alcohol intoxication or suicidal intent were factors at the time of Paraquat ingestion in 75% of the cases. The majority of cases had learned to use Paraquat from a friend; none had been instructed by a professional. Eighty percent of cases did not know the dilution for the proper use of the herbicide, and none kept the herbicide in its original container. Attention to the law, redesign of the Paraquat packaging, and educational efforts directed at populations at risk might reduce the occurrence of poisoning in this region.

Female

Immunosuppression by an immunogenic immunomodulating mycobacterial fraction is correlated to changes in phenotype distribution of murine lymphoid cells.

Previously reported studies revealed that extensive immunization with the Methanol Extraction Residue (MER) of BCG tubercle bacillus in Incomplete Freund's Adjuvant (IFA) induced marked suppression of T and B cell functions in vivo and in vitro. The purpose of the present work was to determine whether immunosuppression induced by hyperimmunization with MER is correlated with changes in morphological characteristics and in phenotype pattern of spleen and peritoneal lymphoid cells. Hyperimmunization with MER resulted in a marked increase in the number of spleen cells and in enlargement and granulation of spleen and peritoneal cells. Similar changes in size and granulation were also observed in isolated fractions of splenic T and B cells. Extensive immunization with MER also induced marked decrease in the total number of T cells (Thy 1,2 positive). The decrease in T cells was observed in all three T-cell subsets investigated: Lyt-1, Lyt-2 and L3T4 positive. Although the number of splenic B cells was decreased in samples (10,000 cells), taken from MER hyperimmunized mice, this decrease was compensated by overall increase in the number of spleen cells. The marked decrease in the percentage of splenic T cells was counterbalanced by marked increase in the splenic macrophage population: increase in MAC-1, MAC-2 and MAC-3 positive cells. It is concluded that extensive immunization with MER induces morphological changes in spleen and peritoneal cells, marked decrease in the number of splenic T cells and marked increase of the splenic macrophagic population. It is postulated that these changes are correlated with induction of immunosuppression by a similar procedure of extensive immunization with the agent.

Animals

Immunological reactivity to a mycobacterial fraction is associated with nonspecific suppression of immunological responsiveness in vivo.

Previously reported studies revealed that spleen cells from BALB/c mice immunized against a methanol extraction residue (MER) fraction of tubercle bacilli are defective in the in vitro generation of antibodies to SRBC and in allogeneic responsiveness against C57BL spleen cells. We now show that mice repeatedly immunized with MER also exhibit a depressed capacity to respond to antigenic stimulation in vivo. Thus mice repeatedly injected with MER were impaired in their ability to react to antigenic stimulation by SRBC and by C57BL spleen cells. Impairment in the response to SRBC immunization was expressed at the level of delayed-type hypersensitivity (DTH) as well as of antibody production. The response of MER hyperimmunized mice to contact sensitization with dinitrofluorobenzene (DNFB) was not impaired, but the lymph node cells of DNFB-sensitized animals had a depressed ability to respond to in vitro stimulation by the monovalent hapten dinitrobenzene sulfonate (DNBS). The present findings indicate that extensive exposure to an immunogenic immunomodulating mycobacterial fraction can lead to a depressed responsiveness to unrelated antigenic stimulation.

Animals