[Evaluation of digestive function in diabetics by cytochemical examination of stools].
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Biomedical subjects
Publications and source records attributed to A Capron.
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The study of antibody-dependent cellular cytoxicity mechanisms in human and experimental schistosomiasis has revealed the particular role of immune complexes in triggering phagocytic cell activation. IgE complexes or aggregates were demonstrated to bind to specific receptors on rat macrophages as well as on human or baboon macrophages, leading to the killing of the parasite target. In the eosinophil-dependent cytotoxicity mechanisms, IgE complexes have been shown to exert a regulatory effect on eosinophil activation in vitro and in vivo and on the ability of this cell population to kill parasites. The various observations reported in this review suggest that the characteristics of the Fc receptors, the composition and antigen-antibody ratio of immune complexes might be essential factors in the regulation of the immune response against parasites.
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The production of immunoglobulins has been studied in Nude (rnu/rnu) rats as well as in their controls (RNU/+). A prototype of humoral T-dependent immune response, the anti-DNP-OVO reaginic production was found very low in Nude rats by comparison to their controls. The percentage of Ig-bearing cells in mesenteric lymph nodes was increased to about the double of those of the control. This percentage can be explained by the absence or at least the great depletion of the thymus derived lymphocytes. On the contrary, the Ig serum levels were rather normal and could correspond to T-independent antigenic stimulation and to membrane immunoglobulin shedding, at least for the IgE isotype.
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We described a baculovirus expression system for high level production of secreted murine recombinant IL-4. We have constructed a recombinant baculovirus based on Autographa californica polyhedrosis virus, containing both a synthetic PCR-derived murine IL-4 cDNA under the control of the polyhedrin promoter and the lacZ gene under the control of the P10 promoter to allow an easy detection of recombinant virus. The baculovirus IL-4 was fully functional in biological assay and was present under two glycosylated forms in the supernatants of infected Sf9 cells. We also detected a third unglycosylated intracytoplasmic form resulting from a fusion between the 35 first amino acids of polyhedrin and the murine IL-4. Finally, confocal microscopy showed that this recombinant protein was secreted along a classical pathway like in mammalian cells.
Parasite escape mechanisms may depend upon factors intrinsic to parasites (host antigen uptake, antigenic variation) and upon partial failure of host's immune mechanisms. Impairment of immune response in parasitic infections, analysed and discussed from literature (138 references), is characterized by a high prevalence of autoantibodies and the common observation of immunosuppression in human parasitic infections as well as in experimental models. The high prevalence of autoantibodies accompanying increased levels of immunoglobulins contrasts with the low prevalence of autoimmune diseases in parasitic endemic areas. Evidence for cell mediated autoimmune process has rarely been reported. This might be related to an impairment of T-helper cell function and to the direct role, on B cells, of mitogens from parasite origin. Immunosuppression has been described in many human parasitic infections and in numerous experimental models. The defect in host's immune response is expressed by an impairment of both humoral and cell mediated immune responses to various heterologous antigens, and increased susceptibility to tumorigenesis, prolonged survival of skin allografts and an increased susceptibility to bacterial or viral infections. Various mechanisms of immunosuppression have been described, including failure of macrophage function or release of soluble immunosuppressive factors by parasites. The authors report some of their recent experiments in experimental schistosomiasis, which have allowed the characterization of such factors. Parasites appear in general to play a role in the regulation of the immune response that they have themselves evoked.
Immunosuppressive factors were evidenced in cell-free supernatant of S. mansoni schistosomes culture and incubation products of the parasite. Both parasitic materials decreased tritiated thymidine and leucine uptake in normal spleen cells from CBA mouse and Fischer rats and in peripheral human blood lymphocytes stimulated either by non specific mitogens (PHA, ConA, or LPS) or by allogeneic cells. The suppressive factor(s) was (were) heat-resistant, dialyzable and of molecular weight 500-1,000. The inhibition of lymphocyte proliferation was not due to cytotoxic or cytostatic activity on lymphoid cells, nor did the parasitic reagents interfere with the binding of fluorescein-labelled ConA. The suppressive activity was also demonstrated in the serum from rats infected for 4 weeks by S. mansoni and in the dialyzable fraction of it. This suggests the release by the parasite in vitro as well as in vivo of inhibitory factor(s) decreasing lymphocyte proliferation and brings therefore a new light on the machanism of immune deficiency in parasitic infections.
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