Antibody-dependent cell-mediated cytotoxicity against parasites.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Capron.
Explore the source record for details and available documents.
Rat IgG2a monoclonal antibodies have been produced after fusion of spleen cells from LOU/C rats infected with S. mansoni for 5 wk and IR983F nonsecreting rat myeloma cells. The cell supernatants of one particular IgG2a-producing clone (IPL Sm1) as well as ascitic fluids induced by this clone revealed anti-S. mansoni activity detected by immunofluorescence on schistosoma sections. In vitro studies of the effector function of such antibodies revealed that the rat IgG2a monoclonal antibodies mediated high levels of rat eosinophil-dependent cytotoxic effect against S. mansoni schistosomula, similar to that obtained with 5-week infected rat serum. Passive transfer experiments carried out with IPL Sm1 ascitic fluid showed a significant level of passive protection against a challenge infection. These results indicate a possible use of the monoclonal antibodies in analyzing in vivo functions of IgG2a antibodies, as well as in isolating potentially protective target antigens.
Certain mast cell products, including the tetrapeptides Ala-Gly-Ser-Glu (Ala4) and Val-Gly-Ser-Glu (Val4) of the eosinophil chemotactic factor of anaphylaxis (ECF-A) and histamine, are preferentially chemotactic for eosinophils in vitro. Amino acid substitutions or modifications of the ECF-A tetrapeptides may substantially alter the chemotactic activity of human eosinophils. The cellular mechanism whereby ECF-A tetrapeptides enhance IgG-dependent killing of schistosomula by rat eosinophils is, however, unclear. We now report that the parent tetrapeptides and the substituted analogue Val-Pro-Ser-Glu (Pro3), but not histamine, increase the number of rat and human eosinophils that form rosettes with erythrocytes bearing IgG antibodies. Moreover, we find a correlation between the effect of these substances on the expression of rat eosinophil IgG Fc receptors and their capacity to increase the IgG-dependent cytotoxicity of rat eosinophils for Schistosoma mansoni schistosomula.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Hydatidosis is not rare in France and often poses diagnostic problems to practitioners. In addition to classical clinical and radiological data, immunological methods provide at the present time reliable means of confirming the diagnosis and conducting post-therapeutic surveillance. After a brief epidemiological and clinical review, the authors review the different laboratory techniques available and report their experience involving 139 cases collected over a period of 2 years. Emphasis is placed upon the relatively high prevalence of the disease amongst immigrant workers, as oppossed to the rare cases seen in the native population, as well as the value of immunoelectrophoresis and conditioned haemagglutination reactions. New therapeutic possibilities offered by mebendazole and its derivatives are indicated.
A sensitive assay, using [14C]lecithin as a substrate, has been developed for the measurement of phospholipase activity in rat peritoneal polymorphonuclear leukocytes. Cell extracts were found to contain a phospholipase D activity and indirect evidence suggested that eosinophils are responsible for the cleavage of lecithin. Intact peritoneal cells were also able to hydrolyze exogenous [14C]lecithin in vitro. When [3H]choline-labeled schistosomula were used as targets in antibody-dependent cytotoxicity experiments, the radioactivity of lecithin decreased more rapidly in a complete cytotoxicity system than in controls, suggesting that hydrolysis of schistosomula phospholipids occurred during the killing process.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Complement-dependent cytotoxic antibodies were found in 54% of Schistosoma mansoni infected patients from Burundi and in 69 to 78% of Schistosoma mansoni ninfected Brazilian patients. The levels of cytotoxic Ab were not statistically different in sera from infected mothers and from their newborn children, suggesting a transfer through the placenta. A sandwich radioimmunoassay (SRIA) and the Radioimmunoprecipitaion-PEG assay (RIPEGA) technique were used in order to detect respectively total schistosome circulating soluble antigens (CSA) and schistosome antigen '4' in sera from infected patients. An inverse relationship was found between the presence of cytotoxic Ab and both total CSA and antigen '4'. The cytotoxic Ab and total CSA levels were followed in five Erythrocebus patas monkeys for 30 weeks after Schistosoma mansoni infection. As in human schistosomiasis the presence of cytotoxic Ab was found to be inversely correlated with the presence of total CAS. The blocking role of Schistosoma mansoni antigens in a complexed form was suggested by the inhibitory effect of the ultracentrifugation pellet of infected human serum on the cytotoxic activity. Moreover, the CSA absorption of infected monkey serum by passage through an anti-CSA immunosorbent significantly increased the cytotoxic activity. Possible mechanisms for the inhibitory role of circulating immune complexes on complement-dependent cytotoxic activity are discussed.
Explore the source record for details and available documents.
Antibody-dependent cell-mediated cytotoxicity in reinfection immunity to schistosomes in the rat involves either IgG2a anaphylactic antibody and eosinophils or IgE antibody and macrophages. The first system requires two signals, one by the antibody through the eosinophil Fc receptor, another by mast cells through the release of mediators among which is ECF-A. IgE antibody complexed with schistosome antigen binds to an IgE-specific receptor on the macrophage and triggers the cell to release enzymes and superoxide. Immunity in rat schistosomiasis is antibody-dependent, abolished in anti-mu treated neonate rats or by passive serum transfer after selective depletion of either IgG2a or IgE. The two anaphylactic antibody-dependent cell cytotoxicity systems are in a permanent balance in immune rats, eosinophils being blocked by IgG2a immune complexes when this cell is inefficient. Anaphylactic antibodies thus play a key role in triggering and modulating effector cell function.
The effect of neonatally initiated injections of anti-mu serum on immunity to reinfection with Schistosoma mansoni in the rat was investigated in vitro and in vivo. Anti-mu treatment resulting in a profound depression of immunoglobulin synthesis dramatically decreased immunity to reinfection assessed by worm recovery technique. Complement-dependent antibody, IgG2a antibody-eosinophil-mediated and IgE-macrophage cytotoxicity reactions were in parallel markedly reduced. These results show the prominent role played by antibody-dependent mechanisms in immunity to schistosomes in the rat.