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Biomedical subjects

S Ben-Efraim

Publications and source records attributed to S Ben-Efraim.

At least 127 records · Page 7Linked to original sources
PubMed1966

Immunochemical studies on the antigenic determinants required to elicit delayed and immediate hypersensitivity reactions.

Hartley and strain 2 guinea pigs were sensitized to chemically defined alpha-DNP(Lys)(n)-BuAm, alpha-DNP(Lys)(n)-, and (Lys)(n)-BuAm peptides and skin tested with individual members of these homologous series, related peptides and hapten-substituted proteins. The immediate skin response (Arthus) could be elicited with hapten-substituted tetra-, penta-, or hexamers, whereas both immediate and delayed skin responses could be provoked by the octamer or nonamer. The hapten is an integral part of the determinant for both immediate and delayed skin reactivity, since poly-L-lysine was unable to elicit either delayed or immediate reactions in sensitized animals. Arthus type cross-reactions occurred only when the sensitizing and test antigen shared a common haptenic determinant. In contrast to this, in this system, delayed type cross-reactions occurred only when the test antigen and the sensitizing antigen contained both a large oligo-L-lysine carrier as well as the same haptenic determinant. These observations imply that the mediation of the delayed response requires a larger determinant than is necessary to elicit the immediate response. The role of high affinity antibody as the mediator of the delayed response is discussed in terms of the size of the antigenic determinants required to elicit this response. It was found that the ability to elicit the delayed response paralleled the immunogenic capacity of these peptides, whereas the immediate response could be elicited by nonimmunogenic peptides. This finding suggests that the delayed response may require the continued biosynthesis of antibody and may be analogous to a local in vivo secondary response.

Animals↗
PubMedDate not supplied

Modulation of antitumour activity of macrophages by regulation of eicosanoids and cytokine production.

Production and release of arachidonic acid (AA) compounds (eicosanoids: prostaglandins-cyclooxygenase and leukotrienes-lipoxygenase) and monokines (TNF-alpha, IL-1 and others) play an essential role in the expression of antitumour activity of macrophages (MO). We investigated the possibility of inducing the antitumour activity of peritoneal murine and human MO by regulating their production of eicosanoids and monokines. The antitumour activity of MO was inversely correlated to production of PGE2 and directly correlated to production of leukotrienes (LTC4 and LTD4). Thus, indomethacin rendered murine MO cytostatic against tumour cells and enhanced the antitumour activity of human peritoneal macrophages from renal patients on CAPD (continuous ambulatory peritoneal dialysis), and leukotriene inhibitors (NDGA-nordihydroguaiaretic acid and AA861) prevented antitumour cytostatic activity of MO. Human peritoneal MO collected during periods of inflammation (infectious peritonitis) were more active against tumour cells, especially when cultured in the presence of LPS, and their activity was correlated to increase with the release of TNF and of IL-1 beta. Human peritoneal MO from inflammation-free patients reacted against a human tumour cell line if cultured with LPS and TPA (phorbol-myristate acetate) and were therapeutically effective against the same palpable s.c. tumours implanted in nude mice.

Cytokines↗
PubMedDate not supplied

One hundred years of cancer immunotherapy: a critical appraisal.

First attempts of cancer immunotherapy were made approximately 100 years ago on the assumption that tumor cells are recognized as 'foreign' by the immune system. Later on, a whole series of experimental animal tumor models were developed. They included the use of syngeneic tumors, spontaneously arising tumors and human tumor xenografts in immunodeficient mice. The experimental data contributed to our understanding of the interaction between immunocompetent cells and their products on the one hand and tumor cells on the other. On this basis, various immunotherapeutic protocols have been devised which included the use of 'nonspecific' components such as bacterial adjuvants, cytokines, NK cells and macrophages and attempts were made to raise specific T and B cell responses against tumor cells. Many human tumor-associated antigens have been characterized, and various ways of increasing the immunogenicity of human tumor cells have been described. Moreover, more insight has been achieved in defining 'high risk' populations on the basis of genetic background, the role of environmental factors and the characterization of 'precancerous' cells. Some cancer vaccines have been used in clinical trials which have resulted in partially beneficial therapeutic effects but have not provided a full solution for a rational use of immunotherapy against human neoplasia.

Animals↗
PubMedDate not supplied

Immunosuppression in vitro and in vivo by supernatants from murine lymphoma cell lines.

Supernatants from four murine B and one T-cell lymphoma cultures were tested for their suppressive effect on allogeneic response in vitro (MLR), on their effect on mitogenic response to ConA and LPS and on their effect in vivo on allogeneic stimulation of BALB/c mice by C57BL/6J spleen cells. Two out of four B-cell supernatants (WEHI-231 and 24-666) were also tested for their effect on induction of IL-2 like activity by ConA in BALB/c spleen cells and on the effect of their injection on subsequent allogeneic response of spleen cells from BALB/c mice immunized against C57BL/6J spleen cells. The supernatants from all lymphoma lines inhibited MLR but only supernatants from the B-cell lymphoma lines also inhibited mitogenic stimulation in vitro and allogeneic immunization. The two B-cell supernatants tested also inhibited induction of IL-2 like activity and decreased the ability of spleen cells from the injected mice to respond to allogeneic stimulation. Partial characterization of supernatants from WEHI-231 and 24-666 lymphoma cultures revealed the non-protein nature of the suppressor factor(s), indicated a molecular weight of less than 5 Kd and suggested a ganglioside or a sialyated glycoproteinic nature.

Animals↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Induction of protective antitumor immune response against a murine plasmacytoma not curable by alkylating-drug treatment.

Immunization with viable tumor cells followed by subsequent administration of glutaraldehyde-treated tumor cells induced a protective antitumor immune response in the host toward the alkylating-drug resistant RPC-5 plasmacytoma. This was proven by resistance to challenge with RPC-5 tumor cells, neutralization in Winn tests, by effectiveness of combined chemotherapy with melphalan plus immunotherapy with spleen cells from RPC-5 immunized mice and in vitro by cytotoxicity tests. The specificity of the immune response was ascertained in vivo by comparison with the response toward MOPC-315 plasmacytoma. However, in vitro cytotoxicity tests revealed the occurrence of shared antigens between the RPC-5 and MOPC-315 tumor cells. It is concluded that the ineffectiveness of alkylating-drug treatment toward the RPC-5 tumor is not due to the inability of this tumor to induce a specific antitumor immune response, and that cross-antigenic relationship as revealed by in vitro cytotoxicity tests does not necessarily reflect cross-protection between various plasmacytomas.

Animals↗
PubMedDate not supplied

Immunocompetence status as related to growth progression of mouse MOPC-315 plasmacytoma.

The immunocompetence status of mice bearing MOPC-315 plasmacytoma was determined at various days after tumor inoculation. Changes in T and B-cell functions appeared gradually. The allogeneic response of spleen cells from BALB/c tumor-bearing mice against C57BL spleen cells was impaired from the 4th day after the tumor inoculation (nonpalpable tumor stage). The primary antibody response in vitro against SRBC was depressed at 18 days, and the mitogenic response of splenic cells to PHA and to LPS was depressed at 25 days after the tumor inoculation. T cells taken from day 18 tumor-bearing mice partially suppressed the MLR response of normal splenocytes. Mice bearing large MOPC-315 tumors responded less to SRBC immunization than normal, noninoculated mice. The relative percentage of Lyt 1, Lyt 2 and L3T4 T-cell subsets decreased starting from the 11th day after tumor inoculation.

Animals↗
PubMedDate not supplied

Classification of anticancer chemotherapeutic drugs according to their immunopotentiating activity.

Both melphalan (L-PAM: L phenylalanine mustard) and 5-fluorouracil (5-FU) expressed a cytotoxic effect in vitro on MOPC-315 plasmacytoma tumour cells. However, they differed in their chemotherapeutic effectiveness in BALB/c mice bearing large MOPC-315 plasmacytoma tumours. Therapy with L-PAM, 7.5 mg/kg induced permanent regression of tumours, whereas regression induced by 5-FU, 200 mg/kg, was only transient and the mice dies finally with tumours. Moreover, spleen cells of tumour bearing mice treated with L-PAM exhibited high specific cytotoxic potential in vitro whereas spleen cells from tumour bearing 5-FU treated mice were devoid of cytotoxic potential. Effectiveness of chemotherapy with L-PAM was antagonized by treatment in combination with 5-FU. L-PAM, but not 5-FU potentiated cell mediated contact sensitivity response in vivo and impaired induction of T-suppressor cells by ConA. The parameters mentioned above indicate that L-PAM behaves as an "immunopromoting" drug and 5-FU as a "nonimmunopromoting" drug.

Adjuvants, Immunologic↗