Asunto(s)
Schistosoma mansoni/inmunología , Esquistosomiasis/inmunología , Linfocitos T/inmunología , Animales , Heces/parasitología , Femenino , Sueros Inmunes/farmacología , Terapia de Inmunosupresión , Intestinos/parasitología , Ratones , Ratones Endogámicos CBA , Oviposición , Recuento de Huevos de Parásitos , Schistosoma mansoni/fisiología , Esquistosomiasis/parasitologíaAsunto(s)
Enfermedades Parasitarias/epidemiología , Adolescente , Adulto , Factores de Edad , Animales , Niño , Egipto , Eucariontes/aislamiento & purificación , Heces/parasitología , Femenino , Helmintos , Humanos , Masculino , Persona de Mediana Edad , Piel/parasitología , Especificidad de la Especie , Orina/parasitologíaRESUMEN
Within seven weeks of infection with 200 Schistosoma mansoni cercariae, T-cell deprived mice have been shown to suffer from extensive microvesicular damage to hepatocytes, and an inability to excrete parasite eggs at the same rate as comparably infected, immunologically intact controls. Administration of serum (CIS) from chronically infected, immunologically intact donors prevented the development of microvesicular cell damage and partially restored egg excretion rates in infected deprived mice. Serum pools obtained from mice injected either with intact S. mansoni eggs or with a homogenate of eggs emulsified in Freund's complete adjuvant (FCA) were as effective as CIS in preventing hepatotoxicity and restoring the rate of egg excretion in infected deprived recipients. The degree of protection of liver tissue afforded by immune sera could be monitored either by histopathological examination of liver sections or by estimation of serum transaminase concentrations, the results from both assays being generally in agreement. Sera from donor mice injected with cercarial or worm antigens in FCA were relatively inactive either in protecting against S. mansoni-induced liver damage or in reconstituting egg excretion rates in infected deprived mice. Serum from donor mice infected with 25 cercariae became hepato-protective between 49 and 53 days after infection of the donors, and the degree of hepatoprotective activity and egg excretion reconstituting capacity in the serum of 25 cercariae-infected donors was shown to increase between 8 and 16 weeks after infection. Increasing the size of infection of the serum donors to 100 cercariae gave only a marginal increase of hepatoprotective activity at 7 weeks when compared with serum donors infected with 25 cercariae for 7 weeks. Liver parenchymal cells of very heavily infected, immunologically intact mice were found to show microvesicular damage similar to that in livers of infected deprived mice, and administration of CIS to these normal mice was histopathologically protective. However, the elevated serum transaminase concentrations obtaining in the infected normal mice were not reduced to any extent by CIS. The results obtained from serum-reconstituted deprived mice are discussed in terms of the contribution they may make to a better understanding of the host-parasite relationship in immunologically intact mice.
Asunto(s)
Hepatopatías/inmunología , Linfocitos T/inmunología , Animales , Interacciones Huésped-Parásitos , Hepatopatías/parasitología , Hepatopatías/patología , Ratones , Ratones Endogámicos , Recuento de Huevos de Parásitos , Schistosoma mansoni/inmunología , Esquistosomiasis/parasitología , Esquistosomiasis/patologíaRESUMEN
Mice infected with from twenty to fifty Schistosoma mansoni cercariae were found to have elevated serum IgG concentrations following patency of the infection, and the parasite-induced increase in concentration of IgG was dependent on the possession by the host of an intact T-cell lymphocyte pool. Following passive transfer of hyperimmune anti-sheep erythrocyte (SRBC) antibody, there was a more rapid decrease of haemolytic and haemagglutinating antibody titres in S. mansoni-infected, immunologically intact recipients than in uninfected intact mice, and infected or uninfected T-cell deprived mice. However, primary and secondary active immunization with SRBC resulted in similar patterns of serum antibody titre increase and decay in infected and uninfected intact mice over a time course of 140 days. The number of direct and indirect haemolytic plaque-forming (PFC) cells per million spleen cells was similar in S. mansoni-infected and uninfected immunologically intact mice 6 days after either primary or secondary challenge with SRBC. It is concluded that S. mansoni-infected immunologically intact mice challenged with heterologous erythrocytes synthesize anti-erythrocyte antibody at a greater rate than similarly challenged, uninfected mice.
Asunto(s)
Inmunoglobulina G/biosíntesis , Esquistosomiasis/inmunología , Linfocitos T/inmunología , Animales , Formación de Anticuerpos , Especificidad de Anticuerpos , Eritrocitos/inmunología , Inmunización Pasiva , Inmunodifusión , Inmunoelectroforesis , Ratones , Ratones Endogámicos CBA , Recuento de Huevos de Parásitos , Schistosoma mansoni/inmunología , TimectomíaRESUMEN
Normal mice developed marked elevation of two acute phase plasma proteins, C3 and serum amyloid P-component (SAP), between 40 and 50 days after percutaneous infection with cercariae of Schistosoma mansoni. The high levels persisted until the end of the experiment (day 106). The onset of this acute phase response corresponds with the reported time at which granulomata develop in the liver. In mice deprived of T cells by thymectomy and anti-thymocyte serum, the granulomata were significantly smaller and all the animals died between days 70 and 80. These mice had normal C3 levels throughout although there was a rise in SAP concentration. C3 and SAP levels in infected control mice, which had been thymectomized but not deprived of T cells with anti-thymocyte serum, were the same as in intact infected animals. The different behaviour of C3 and SAP in infected T-cell deprived mice may reflect the alteration in specific schistosomal pathology and/or a role for T cells in mediation of the acute phase production of some proteins.
Asunto(s)
Amiloide/sangre , Complemento C3/metabolismo , Esquistosomiasis/inmunología , Linfocitos T/inmunología , Animales , Granuloma/inmunología , Hepatopatías/inmunología , Masculino , Ratones , Schistosoma mansoni , Esquistosomiasis/sangre , TimectomíaRESUMEN
The effects of various immunosuppressive regimes on the survival and liver pathology of mice infected with Schistosoma mansoni were investigated. T-cell deprivation before infection (by adult thymectomy and subsequent anti-thymocyte serum administration), or treatment with hydrocortisone or cyclophosphamide or azathioprine after infection, all reduced survival of infected mice when compared with immunologically intact, infected mice. T-cell deprivation or steroids produced severe liver damage in infected mice despite a reduction in the size of the peri-oval granulomatous inflammatory reaction. Administration of chronic infection serum reduced liver damage in both T-cell-deprived and steroid-treated animals, but improved survival only in the deprived animals and not to the level seen in normal infected mice. The liver damage in immunosuppressed mice was not due to opportunistic bacterial infection. Thus, although immunosuppression reduced the granulomatous response to schistosome eggs in the livers of infected mice (as it does to eggs injected intravenously into the lungs), survival time was decreased. The relevance of these findings to human S. mansoni infections is discussed.
Asunto(s)
Esquistosomiasis/inmunología , Animales , Suero Antilinfocítico/uso terapéutico , Hidrocortisona/uso terapéutico , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Hígado/patología , Ratones , Ratones Endogámicos CBA , Schistosoma mansoni , Esquistosomiasis/patología , Esquistosomiasis/terapia , Linfocitos T/inmunología , TimectomíaRESUMEN
Mice which had been thymectomized and injected with anti-thymocyte serum to remove long-lived recirculating T cells, initially failed to produce haemagglutinating and haemolysing antibody after injection of sheep erythrocytes. After six fortnightly injections of heterologous erythrocytes, however, haemolysin titres in the T-cell deprived mice were comparable to those in similarly challenged but immunologically intact animals. Isoelectric focusing of these sera indicated that the anti-sheep erythrocyte antibody eventually synthesized by the T-cell deprived mice was less heterogeneous than antibodies found in the sera of control mice.
Asunto(s)
Anticuerpos Heterófilos/biosíntesis , Linfocitos T/inmunología , Animales , Suero Antilinfocítico/inmunología , Eritrocitos/inmunología , Focalización Isoeléctrica , Ratones , Ratones Endogámicos CBA , TimectomíaAsunto(s)
Inmunidad Celular , Esquistosomiasis/inmunología , Linfocitos T/inmunología , Timectomía , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Peso Corporal , Sueros Inmunes , Hepatopatías/inmunología , Hepatopatías/prevención & control , Ratones , Ratones Endogámicos CBA , Tamaño de los Órganos , Schistosoma mansoni/inmunología , Esquistosomiasis/sangre , Esplenomegalia/etiologíaRESUMEN
Liver changes occurring in mice deprived of their T-cells by a combination of thymectomy and anti-mouse thymocyte serum, and in immunologically intact control mice, were followed during the early stages of heavy Schistosoma mansoni infections. Lesions in both groups began developing by day 38 and were maximal by day 48. Hepatic changes in control mice culminated in large hypersensitivity granulomas, tissue eosinophilia, portal periphlebitis, fibrosis, vascular obstruction, and infarction leading to arterialization and preferential sinusoidal channeling. Deprived mice showed greatly reduced egg reactions composed principally of macrophages, monocytes, and occasional neutrophils, and only minimal alteration of liver architecture; however, focal and disseminated hepatocellular lesions became prominent as the infections progressed, and by day 48 virtually every hepatocyte was affected. Typically, hepatocytes showed microvesicular cytoplasmic damage (steatosis) or ballooning degeneration with accompanying nuclear pyknosis or karyorrhexis. This cellular pathology may be attributed to the direct or indirect effect of eggs or egg products on liver cells. The administration of chronic infection serum obtained from immunocompetent mice to T-cell deprived mice dramatically eliminated the hepatocellular lesions. It also increased eosinophil participation and fibrosis in the egg reactions but did not restore the size and other cellular features typical of egg hypersensitivity granulomas. Serum from uninfected normal mice was found to lack these effects.
Asunto(s)
Inmunidad Celular , Esquistosomiasis/patología , Linfocitos T/inmunología , Animales , Sueros Inmunes , Hígado/patología , Hepatopatías/prevención & control , Ratones , Ratones Desnudos , Reproducción , Schistosoma mansoni , Esquistosomiasis/inmunología , Linfocitos T/patología , Timectomía , Factores de TiempoRESUMEN
CBA mice deprived of their T cells by means of thymectomy and anti-thymocyte serum and subsequently infected with Schistosoma mansoni were found to have substantially fewer parasite eggs in their faeces than similarly infected immunologically-intact control animals. The number of parasite eggs deposited in the tissues of T-cell deprived mice was by comparison only marginally lower than in control mice. Administration of serum obtained from normal mice with chronic S. mansoni infections partially restored the egg excretion rate in infected deprived mice, and also resulted in an increased number of eggs being deposited in the liver and intestine of these animals.