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M Segre

Publications and source records attributed to M Segre.

12 recordsLinked to original sources
PubMed1992

Behavior of the idiotypic network in conventional immune responses. I. Kinetics of idiotypic and anti-idiotypic antibodies following immunization with T-independent and T-dependent antigens.

A minimal requirement in investigations of the behavior of the idiotypic network during immunization is the ability to quantitate both the idiotypic (Ab1) and anti-idiotypic (Ab2) responses. Quantitation of Ab2 in serum is complicated by the simultaneous presence of Ab1, so that Ab1-Ab2 immune complexes escape detection. In contrast, immune complexes should not complicate the enumeration of Ab2-producing lymphocytes in a hemolytic plaque assay. This study utilizes a procedure that allows detection of Ab2-producing cells in such an assay. The procedure relies upon the insertion of the appropriate antibody (Ab1) into the membrane of indicator SRBC through a covalently attached dipalmitoyl phosphatidylethanolamine (DPPE) tail. When the Ab2 response following murine immunization with DNP-Ficoll was analyzed using such an assay, peak plaque-forming cell (PFC) numbers were found to coincide with peak Ab1 PFC numbers in both the primary and secondary response. In addition, this Ab2 response was found to be T independent. The murine immune response to DNP-HGG demonstrated a peak Ab2 PFC response which followed the peak Ab1 PFC response after both primary and secondary immunization. This Ab2 response appeared to be T dependent. The secondary responses to both DNP-Ficoll and DNP-HGG showed increased levels of Ab2 PFC and decreased levels of Ab1 PFC in comparison to the primary responses to the same antigens, suggesting that immunoregulation may occur within these idiotypic networks.

Animals↗
PubMed1992

Behavior of the idiotypic network in conventional immune responses. II. Affinity and heterogeneity of idiotypic and anti-idiotypic antibodies following immunization with T-independent and T-dependent antigens.

The relative affinity and heterogeneity of affinity of idiotypic and anti-idiotypic antibodies in mice immunized with the T-independent antigen DNP-Ficoll and the T-dependent antigen DNP-HGG were measured by a plaque inhibition assay. Idiotypic plaque-forming cells (PFC) were detected by a conventional assay utilizing DNP-coated SRBC. Anti-idiotypic PFC were detected with SRBC coated with affinity-purified anti-DNP antibody of rabbit origin. It was found that both idiotypic and anti-idiotypic antibodies elicited by immunization with the T-independent antigen had lower affinity and were less heterogeneous than the corresponding antibodies originating in mice immunized with the T-dependent antigen. In addition, the affinity and heterogeneity values of the idiotypic antibodies were correlated with the affinity and heterogeneity values of the anti-idiotypic antibodies from the same mice. This finding indicates that idiotypic and anti-idiotypic antibodies mutually regulate each other, thus pointing to internal immunoregulatory effects of the idiotypic network with respect to these parameters.

Animals↗
PubMed1979

Inhibition of the humoral response by spleen cells from cyclophosphamide-treated mice.

Spleen cells obtained from mice injected with cyclophosphamide (200 mg/kg body weight) suppressed the secondary IgG antibody response of memory cells to a T-dependent antigen, DNP-HGG, in Millipore diffusion chambers. Significant suppression (greater than 50%) was found from 5 to 14 days following cyclophosphamide treatment, with peak suppression (86%) on day 7. The primary IgM antibody response to DNP-Ficoll, a T-independent antigen, was not suppressed by these cells. In contrast, suppression was observed in the primary IgM response to sheep red blood cells, a T-dependent antigen. In addition, treatment of the suppressor cell population with anti-Thy-1 serum and complement did not inhibit suppressor activity. We concluded that the suppressor activity was not attributable to a typical T cell, and that the target of suppression was not a B cell. Preliminary evidence suggests that the suppressor activity is regulated, directly or indirectly, by a T cell.

Animals↗
PubMed1978

A time study of the requirement for carrier-specific helper cells in the response of mice to dinitrophenylated keyhole limpet hemocyanin.

The anti-hapten response of spleen cells from mice primed with hapten-carrier (dinitrophenylated keyhole limpet hemocyanin) was decreased by depletion of T cells during the first four days after secondary antigenic stimulation, but was unaffected when the T cells were depleted on day 5. The response of cultures that were depleted of T cells prior to secondary antigenic stimulation was restored by addition of carrier-primed cells during the first two days of culture, partially restored on day 3, but not at later times. Thus, T cells were required only at about day 4 of a secondary response to a T-dependent antigen that peaked on day 8. Autoradiography experiments showed that the frequency of antigen-binding cells increased with time regardless of the presence of T cells in the cultures. We conclude that helper T cells are not required for B cell proliferation, but are required for the differentiation of B cells to antibody-secreting cells.

Animals↗
PubMed1976

Humoral immunity in aged mice. I. Age-related decline in the secondary response to DNP of spleen cells propagated in diffusion chambers.

The secondary response of young-adult and old BC3F1 mice to DNP was assessed by boosting spleen cells from primed mice with DNP-KLH, propagating them in diffusion chambers implanted into irradiated recipient mice, and by counting the DNP-specific PFC. There was no difference between young-adult and old cells in the antigen dose response and in the kinetics of the immune response. There were marked differences in the magnitude of the peak response. The response of 2-year-old mice was significantly smaller than the response of young-adult mice. Two and one half-year-old mice had the smallest response. In the old mice, there was an inverse correlation between the number of nucleated cells in the spleen and the log of the number of PFC.

Aging↗
PubMed1976

Humoral immunity in aged mice. II. Increased suppressor T cell activity in immunologically deficient old mice.

Mixed cultures of DNP-primed spleen cells from old and young BC3F1 mice in diffusion chambers yielded significantly fewer secondary PFC than expected from the numbers of PFC found when young and old spleen cells were cultured alone. There was a negative correlation between the log of the number of PFC found in cultures of old spleen cells alone and the degree of immunosuppression exerted by the cells. The immunosuppressive effect was abolished by pretreatment of the old spleen cells with anti-theta serum and complement. Thus, the effect was attributed to the presence of large numbers of suppressor T cells in the spleen of primed old mice. No suppression was found in mixed cultures of spleen cells from old unimmunized mice and young primed mice.

Aging↗
PubMedDate not supplied

Age-related changes in B and T lymphocytes and decline of humoral immune responsiveness in aged mice.

The activity of the immune system declines in an age-related fashion, after reaching a peak in young-adult animals. Although this pattern has been well documented, the mechanisms responsible for the decline of immune potential in senescence have not been fully elucidated. At the same time, it has become apparent that the immune response depends on complex interactions among different cell types. We review the results of the analyses of B- and T-lymphocyte function and activity in the humoral responsiveness of aged mice that have been performed in a number of laboratories, with a variety of experimental techniques. We conclude that an increase in T-cell suppressor function is the first immunologic lesion of aging in mice. This is followed by a decrease in T-cell helper function and finally by a loss of B-cell function.

Aging↗
PubMedDate not supplied

Radiant heat-induced hyperthermia in mice: in vivo effects on the immune system.

Whole-body hyperthermia (WBH) in mice was induced by 2-4-h exposure to radiant heat resulting in core body temperatures of 38.5-40.4 degrees C, and correlated directly with the magnitude and duration of heat treatment. Two-hour heat treatments in this temperature range did not consistently affect generation of antibody-forming cells in vivo, while 4-h treatments at temperatures greater than or equal to 40 degrees C significantly suppressed the antibody-forming cell response. The capacity of lymphocytes from similarly heated mice to generate antibody-forming cells in vitro was not affected, suggesting that the observed in vivo suppression may be mediated by circulating factors rather than by some heat-induced alteration in the cells themselves. In vivo treatment did not alter T-cell responsiveness to the mitogen Con-A or delayed-type hypersensitivity responses to sheep red blood cells. Quantitative and flow cytometric assessment of splenic and thymic lymphocyte numbers showed that WBH did not alter absolute numbers of lymphocytes but did temporarily change the proportions of lymphocyte subsets. An immediate increase in splenic L3T4+ cells was observed, followed within 18 h by an overall decrease in Lyt 2+ and Thy 1.2+ T-cells. In the thymus the percentages of mature T cells increased. In general, only minimal effects of heat on the immune responses of normal mice could be demonstrated.

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