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Biomedical subjects

A Capron

Publications and source records attributed to A Capron.

At least 559 records · Page 31Linked to original sources

Immunoregulation by Schistosoma mansoni.

Schistosoma mansoni is known to release an inhibitory factor of lymphocyte proliferation elicited in vitro. The effect of this dialyzable schistosome incubation product (DSIP) was tested in vivo on different aspects of the cell-mediated immune response. First, the DSIP injected into C57B1/6 mice markedly inhibited the delayed type hypersensitivity to sheep red blood cells (SRBC). Furthermore, the DSIP injected into S. mansoni infected Fisher rats at the beginning of the infection induced an inhibition of the specific lymphocyte response to S. mansoni antigen and of the spleen cell response to concanavalin A (Con A). The DSIP injected into uninfected rats also inhibited the spleen cell response to Con A. In uninfected as in infected rats injected with the DSIP, the lymphocyte response to Con A was restored after purification of the spleen cells on a nylon wool column. Moreover spleen cells from rats injected wtih the DSIP reduced the proliferative response of normal syngeneic spleen cells induced by Con A. This inhibition was not observed when cells from DSIP-injected rats were previously passed through a nylon wool column. In contrast, nylon wool depletion of spleen cells from infected rats injected with the DSIP did not restore the lymphocyte response to S. mansoni antigen. It seems tht DSIP could partly explain the modulation of the cellular immune responses observed during S. mansoni infection and could represent one of the mechanisms of this parasite's survival in the immunized host.

Animals↗

Isolation and characterization of surface antigens from Schistosoma mansoni schistosomula.

Surface antigens of Schistosoma mansoni schistosomula were isolated using antibodies produced in rat and human schistosomiasis. Three immunoreactive surface proteins of 40 000, 37 000 and 32 000 daltons were identified by SDS-PAGE analysis of immune complexes formed by incubation of a detergent extract of surface labelled schistosomula with infected rat sera. Surface antigens of similar molecular weight were also isolated when using sera of patients with schistosomiasis. Binding of schistosomula surface antigens to specific antibodies was substantially inhibited by components released by adult worms. The results suggest that these schistosomula surface antigens could be involved in the immune response against challenge infection but their protective role in immunity still remains to be determined.

Animals↗

Dipetalonema viteae: ultrastructural study on the in vitro interaction between rat macrophages and microfilariae in the presence of IgE antibody.

The in vitro interaction between rat peritoneal macrophages and Dipetalonema viteae microfilariae in the presence of amicrofilaraemic rat immune serum was studied by transmission electron microscopy. The probable sequence of events leading to the killing of D. viteae microfilaria by macrophages is as follows. (a) Rat peritoneal macrophages in the presence of amicrofilaraemic rat immune serum adhere to the parasite surface, (b) the macrophages extend their pseudopodia around the parasite, (c) the 'lysosome-like' granules discharge their contents on to the parasite surface, (d) the lytic activity of these products begins at the parasite surface and (e) subsequent breaking of the microfilarial cuticle occurs, exposing the parasite intracellular material.

Animals↗

Proteolytic cleavage of IgG bound to the Fc receptor of Schistosoma mansoni schistosomula.

After the binding of IgG to the surface Fc receptor of Schistosoma mansoni schistosomula, the Fab portions of IgG are cleaved and small peptides are liberated in the culture medium. At least two types of proteinase activities have been demonstrated in the secretory products of schistosomula. One is an endoprotease with trypsin-like activity, with an optimum pH of 7 and an optimum temperature of 45 degrees C. The other is a metalloaminopeptidase with an optimum pH of 7 and temperature of 37 degrees C.

Chymotrypsin↗

Trypanosoma cruzi infection in B-cell-deficient rats.

The effect of neonatally initiated injections of anti-mu rabbit antiserum on immunity of rats against Trypanosoma cruzi infection was investigated in vivo. Anti-mu treatment resulted in a loss of immunoglobulin M (IgM) and IgG2a synthesis and, subsequently, of antibody production. These rats so treated were shown to be significantly more susceptible to the acute phase of the infection than the control rats treated with normal rabbit serum, as measured by increased parasitemia and mortality. These results indicate the essential role of antibodies, probably in association with complement or effector cells or both, in immunity to acute Chagas' disease.

Animals↗

Correlation between circulating antigens detected by the radioimmunoprecipitation-polyethylene glycol assay (RIPEGA) and C1q-binding immune complexes in human schistosomiasis mansoni.

Circulating schistosome antigens (CSA) and circulating immune complexes (CIC) were investigated in serum from 420 patients infected with Schistosoma mansoni. The radioimmunoprecipitation-polyethylene glycol assay with [125I] anti-S. mansoni rabbit antibodies appeared as a sensitive and specific method to quantify CSA. In fact, more than 75% of the patients showed significant levels of CSA. C1q-binding CIC were also detected in 70% of subjects with schistosomiasis. In addition, a close correlation was observed between levels of CSA and CIC. These data suggest that part of the CIC present in human schistosomiasis are formed by schistosome specific antigens.

Antigen-Antibody Complex↗

Detection of circulating antigens in onchocerciasis.

This report describes the presence of circulating Onchocerca volvulus antigens (COA) in sera of patients with onchocerciasis. By using a double diffusion immunoelectrophoresis method, COA could be detected in 24 of 77 sera analyzed (31%). In contrast, when more sensitive assays such as the radioimmunoprecipitation-PEG assay or sandwich radioimmunoassay were used to detect COA, about 75% of the sera from O. volvulus-infected patients were found positive; moreover, a highly significant correlation between the two assays was observed. The parasite specificity of the COA was demonstrated directly by identity reaction with a component of O. volvulus somatic antigens. COA was never found when hyperimmune antisera against other parasite antigenic extracts were used instead of anti-O. volvulus hyperimmune serum. However, when anti-O, volvulus hyperimmune serum was used against sera obtained from patients infected with various other helminths we found a cross-reactivity between COA and the circulating antigens of other human filarids (Wuchereria bancrofti, Loa loa, Brugia malayi), but not with other nematode or trematode parasites (Ascaris lumbricoides, Schistosoma mansoni, Fasciola hepatica). Further immunoelectrophoretic studies demonstrated one precipitin are localized in the cathodic region which seemed specific for COA, which raises the possibility of preparing a monospecific hyperimmune serum to circumvent cross-reactivities.

Adolescent↗

Circulating immune complexes in human fascioliasis. Relationship with Fasciola hepatica egg output.

Circulating immune complexes were investigated by the 125I-Clq binding test in serum from patients with fascioliasis. Only 36% of all the patients studied showed significant levels of CIC. Nevertheless, when we considered only the patients eliminating Fasciola hepatica eggs in the stool and/or with the acute phase of the infection, the detection of CIC was very higher (more than 70% of the cases). In addition, a close relationship was observed between F. hepatica egg output and the incidence of CIC. This data suggest strongly the occurrence of specific parasite antigens in the detected CIC. The involvement of CIC in the pathogenesis of the acute hepatic fascioliasis is discussed.

Animals↗

Schistosoma mansoni: autoantibodies and polyclonal B cell activation in infected mice.

The appearance of autoantibodies was investigated during the course of Schistosoma mansoni infection in C57Bl/6 mice. Anti-liver autoantibodies or lymphocyte-reactive alloantibodies were detected respectively without cell-mediated immunity against liver antigen or lymphocytotoxic activity. Anti-liver, anti-DNA, anti-Ig and anti-lymphocyte antibodies were shown 6-7 weeks after the beginning of the infection concomitantly with the increase of immunoglobulin levels and circulating immune complexes. At this period, the antibody response to polyvinylpyrrolidone (PVP) was increased and the injection of spleen cells from day-45-infected mice to uninfected recipients increased the anti-PVP antibody response. Conversely, the injection of spleen cells from uninfected to infected mice did not modify the anti-PVP Ab response. After 6 weeks of infection, the basal thymidine incorporation of spleen cells was increased contrasting with the marked inhibition of spleen cell response to PHA. The present data are consistent with the induction of a polyclonal non-specific B cell activation by S. mansoni.

Animals↗

Antibody inducing lymphocyte cytotoxicity (ADCC) and lymphocyte-mediated cytotoxicity in auto-immune thyroid diseases.

Addition of heat-inactivated serum from patients with autoimmune thyroid diseases to normal nonadherent human lymphoid cells caused significant lysis of thyroglobulin or crude thyroid extract-coated erythrocytes. Serum from 9/10 patients with Hashimoto's thyroiditis induced significant chromium release by normal lymphocytes at higher dilution (greater than 1 : 1 000) than in other thyroid diseases, the mean highest positive dilution being 1 : 535 in Grave's disease and approximately 1 : 200 in primary hypothyroidism, hyperthyroidism without exophthalmos and non toxic goitres. Lymphocyte-mediated cytotoxicity in the absence of serum was found positive on one half of the patients with lymphocyte-dependent antibody. Besides an appraisal of autoimmunization in thyroid diseases, such cell-mediated reactions may indicate how the gland is damaged in autoimmune thyroid diseases.

Adolescent↗

Interaction between Schistosoma mansoni and the complement system: role of IgG Fc peptides in the activation of the classical pathway by schistosomula.

It was previously reported that Schistosoma mansoni schistosomula in the presence of IgG activate complement through the classical pathway (CCP). In the present work we have demonstrated that schistosomula incubated with IgG peptides resulting from IgG hydrolysis by schistosomula proteases are able to initiate complement activation through CCP, since a marked consumption of C1, C4, and C2 was observed. Our results eliminate an eventual direct action of the substances released by schistosomula on the activation of CCP. The first step of CCP activation required the preliminary binding of IgG peptides on the schistosomula surface. This interaction induced an increase in the C1q uptake by schistosomula. Since the involvement of the Fc portion of IgG molecules has been clearly evidenced, in this case the peripheral globular subunits of C1q recognize the CH2 region on IgG peptides or intact IgG molecules. By this mechanism, the local consumption of complement around schistosomula could contribute to its survival in the host.

Complement Activating Enzymes↗

Evidence for IgE-dependent cytotoxicity by rat eosinophils.

Human and rodent eosinophils have been shown previously to act as effector cells against Schistosoma mansoni schistosomula by ADCC mechanisms involving IgG antibodies. The present work brings novel evidence for the existence in rat schistosomiasis of an IgE-eosinophil dependent cytotoxicity mechanism. The role of IgE antibodies present in the rat serum after 6 weeks of infection was clearly established by immunoadsorption and inhibition experiments, whereas the participation of IgG and complement in this system could be ruled out. Mast cell products, including ECF-A tetrapeptides, appear to play an essential role in significantly increasing eosinophil cytotoxicity. A kinetic study of the IgG-dependent cytotoxicity mechanism previously described and of this IgE-mediated mechanism according to rat schistosomiasis revealed the preeminent role played by IgG antibodies in early infection, whereas IgE predominated after 6 wk of infection. The possible significance of IgE-eosinophil cooperation in ADCC mechanisms in parasite and nonparasite models is discussed.

Animals↗

Macrophage triggering by aggregated immunoglobulins. I. Delayed effect of IgG aggregates or immune complexes.

Rat peritoneal macrophages in serum-free cultures were triggered to release lysosomal enzymes or plasminogen activator and to incorporate glucosamine upon exposure to rat IgG that was nonspecifically aggregated after heating or by dimethylsuberimidate cross-linking or was specifically complexed by the corresponding antigen using preformed BSA-anti-BSA immune complexes. A lag period of 6 hr was observed before the increase in enzyme release or in glucosamine uptake. Although chemically prepared dimers of IgG were found sufficient to trigger the macrophages, both enzyme release and glucosamine incorporation increased with the size of the IgG aggregates. Similarly, immune complexes in IgG antibody excess (Ag/Ab ratio 1:32) were more efficient than complexes prepared at equivalence or in antigen excess, which suggests that the size of the aggregates is an important parameter of macrophage triggering. The participation of the macrophage Fc receptor for IgG in IgG-dependent macrophage triggering is suggested by similar findings using a first exposure of the cells to rat IgG then the cross-linking the cell-bound immunoglobulin by purified anti-rat IgG or the F(ab')2 fragment of it. Macrophage function in inflammatory reaction might thus be modulated by the size of IgG immune complexes.

Animals↗