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Biomedical subjects

F Kierszenbaum

Publications and source records attributed to F Kierszenbaum.

At least 145 records · Page 8Linked to original sources
PubMed1980

Evaluation of lymphocyte responsiveness to polyclonal activators during acute and chronic experimental Trypanosoma cruzi infection.

The responses of spleen cells from mice infected with Trypanosoma cruzi to T and B cell-specific mitogens were monitored during the acute and chronic stages of the infection. Responses to either T (phytohemagglutinin or concanavalin A) or B (endotoxic lipopolysaccharide) cell mitogens measured on days 5, 10, 15, and 20 postinfection, i.e., at different times during the acute period, were markedly reduced. Responses measured on days 54 and 90, i.e., during the chronic stage, did not differ significantly from those of normal mouse spleen cells. Proportions of T and B lymphocytes in the spleen were reduced and unaltered, respectively, during acute T. cruzi infection but were comparable to normal values during the chronic state. These results highlight a return of normal T and B lymphocyte responses during chronic experimental Chagas' disease and suggest that transition from the acute to the chronic phase of the infection may be immunologically regulated.

Acute Disease↗
PubMed1980

Selective removal of T cell function from mouse lymphocyte suspensions by treatment with normal guinea pig serum.

Treatment of murine spleen cells with normal guinea pig serum selectively abrogated responsiveness of these cells to the T cell mitogens PHA or Con A, but failed to affect responses to LPS, i.e., a B cell-specific mitogen. Although pretreatment with GPS inhibited the in vitro immune response of mouse splenocytes to SRBC, responses were normal after restoration with T cells only, indicating that B cells had been spared by GPS. Consistent with these results, incubation with GPS resulted in the loss of reactivity of mouse lymphoid cells in MLC as well as CML systems, both of which test for T cell activities. Furthermore, parental spleen cells treated with GPS were no longer capable of inducing a GVH reaction in F1 hybrids. When compared, the effects of GPS and anti-Thy-1.2 antibodies plus C were found to be comparable. These results indicate that GPS can selectively remove a number of T cell functions from heterogeneous murine lymphoid cell suspensions. Since spleen macrophages were insensitive to GPS cytotoxicity, lack of T cell function is not likely to be due to depletion of these accessory cells.

Animals↗
PubMed1980

Mechanisms of resistance against experimental Trypanosoma cruzi infection. Requirements for cellular destruction of circulating forms of T. cruzi in human and murine in vitro systems.

The sensitivity of host (circulating) forms of T. cruzi to cell-mediated immunological destruction and requirements for the reaction were examined. Both human and mouse leucocytes were found to kill significant numbers of parasites in the presence of specific antibodies against the flagellates. Antibody involvement was confirmed by the marked ihhibitory effects on cytotoxicity that resulted from the addition to reaction mixtures of either aggregated normal IgG or purified protein A. Similar inhibition was observed when antiserum to T. cruzi was pre-absorbed with an insoluble protein A preparation. In addition, immunoglobulins present in normal mouse serum failed to support cytotoxicity by cells with demonstrated effector capacity in parallel antibody-containing reactions. In this system, human peripheral blood lymphocytes, neutrophils and eosinophils but not adherent mononuclear cells were able to kill T. cruzi. Also active were mouse lymphoid cells, neutrophils and adherent mononuclear cells. Minimal effector:target cell ratios resulting in detectable trypanosome killing were 0 x 2 and 0 x 6 for human and mouse lymphoid cells, respectively. The present results are relevant to the understanding of the possible mechanisms underlying the protective effects of the immune response against T. cruzi infection.

Animals↗
PubMed1979

Thymus-dependent control of host defense mechanisms against Trypanosoma cruzi infection.

Congenitally athymic homozygous (nu/nu) mice were shown to be significantly more susceptible to Trypanosoma cruzi infection than their thymus-bearing heterozygous (nu/+) littermates, as measured by increased parasitemia, mortality rate, and shortened survival time. In addition, transplantation of neonatal thymus into athymic mice reestablished normal levels of resistance to T. cruzi, i.e., comparable to those of normal littermates. These results constitute conclusive evidence that host defense mechanisms active in experimental Chagas' disease are under thymic control.

Animals↗
PubMed1979

Antibody-dependent killing of bloodstream forms of Trypanosoma cruzi by human peripheral blood leukocytes.

Bloodstream forms of Trypanosoma cruzi were found to be destroyed by human lymphoid cells, neutrophils, or eosinophils in the presence of specific antibodies. Nonspecific immunoglobulins present in normal serum did not mediate the cytotoxic reaction. Cells or antibody had no significant lytic effect on the parasite when tested separately and purified, non-activated human adherent cells were inactive antibody was present or not.

Animals↗
PubMed1977

Cytotoxic effects of normal sera on lymphoid cells. II. Requirements for inhibition of nonspecific serum cytotoxicity by agarose.

Agarose is known to inhibit nonspecifically the cytotoxic effects of normal sera on xenogeneic lymphoid cells. To find an explanation for this agarose effect we have studied its requirements using guinea pig and human sera as the source of activity and rat thymocytes as target cells. Control assays were performed using heat-inactivated (56 C, 30 min) normal rat serum. The inhibitory effect of agarose was readily reproduced with untreated sera and also when sodium ethyleneglycoltetraacetate, a selective chelator of calcium ions, was added to the sera together with excess magnesium. However, the agarose effect failed to occur in the presence of 0.01 M EDTA unless magnesium ions were restored. Abrogation of cytotoxicity in human serum by incubation with a large number of target cells instead of agarose was also found to be magnesium dependent. Titrations of human serum, performed after absorption with agarose in the presence of EDTA, which does not interfere with antigen-antibody binding, and subsequent restoration of divalent cations, revealed no significant change in its cytotoxic titer when compared with that of mock-absorbed serum not subjected to the agarose treatment. Incubation of human serum with either agarose or rat thymocytes resulted in the conversion of factor B, essential for complement activation via the alternative pathway, previously shown to provide the complement activity necessary for the cytotoxic reaction. These results suggest that the agarose effect is mainly attributable to complement consumption via the alternative pathway rather than to the absorption of "natural" antibodies.

Animals↗
PubMed1977

Antibody-independent activation of the alternative complement pathway in human serum by parasitic cells.

The lysis of the monocellular parasite Trypanosoma cyclops by normal human serum (NHS) was found to be complement-dependent and to follow activation of the alternative pathway without apparent requirement for conventional antibodies. Lysis of the organisms was inhibited by heat-inactivating NHS at 56 degrees, preincubation of NHS with cobra venom factor or chelation of divalent cations with EDTA. It took place, however, in human C2-deficient serum and was inhibited by prior heating of NHS at 52 degrees to destroy the activity of factor B of the alternative pathway. Moreover, the lytic reaction was magnesium- but not calcium-dependent. Repeated low-temperature (0 degrees) absorption of either human hypogammaglobulinaemic serum or NHS with the parasite failed to remove or significantly decrease their lytic activities.

Complement System Proteins↗
PubMed1976

Mechanisms of natural resistance to trypanosomal infection. Role of complement in avian resistance to Trypanosoma cruzi infection.

The natural resistance of chickens to Trypanosoma curzi infection and the capacity of their sera to lyse blood (trypomastigote) forms of the parasite in vitro were found to be complement-dependent phenomena. Parasites given intravenously to decomplemented chickens were detectable in their bloodstream for at least 24 h post-infection, whereas in untreated animals they became undetectable after 1 min (and destroyed flagellates were observed). One millilitre of serum had the capacity to lyse as many as 10-30 X 10(6) organisms. The lytic activity of serum in vitro was not impaired in chickens that had been immunosuppressed by four different procedures and was present in the absence of antibodies. In vitro lysis of T. cruzi by either normal or antibody-free chicken sera occurred in the absence of calcium ions but required magnesium ions, indicating that complement was activated via the alternative pathway. Administration of normal chicken serum to mice infected with T. cruzi provoked a marked decrease in their parasitaemias.

Animals↗
PubMed1976

Mechanisms of resistance against experimental Trypanosoma cruzi infection: the importance of antibodies and antibody-forming capacity in the Biozzi high and low responder mice.

The role of antibodies and the host's antibody-forming capacity in resistance to Trypanosoma cruzi infection has been investigated in the Biozzi high and low responder lines of mice. Ab/L animals with low antibody-forming capacity were found to be more susceptible to i.p. infection with trypomastigotes than high responders (Ab/H), whereas non-selected Swiss albino mice showed an intermediate level of susceptibility. The correlation between antibody-forming potentiality and susceptibility was consistently observed with both the Y and Tulahuén strains of the parasite, which differ in their preferential tissue tropism as well as virulence. A similar divergence in susceptibility was observed after subcutaneous infection with the Y strain which produced a more fulminating disease. Although Ab/L mice neither produced a significant antibody response to the parasite nor responded to prophylactic immunization with killed T. cruzi epimastigotes, they could be effectively protected by passive transfer of immune plasma.

Animals↗