Hematological changes in mice experimentally infected with Trypanosoma Cruzi

Mice inoculated with trypanosoma cruzi display an intense thrombocytopenia which is more severe in animals infected with the Y than CL strain. In animals inoculated with a T. cruzi strain which induces chronic infection (Colombiana), the number of platelets decreases as parasitemia ascends, and then reverts to normal values as soon as the acute infection merges into the chronic phase. The mechanisms involved in the thrombocytopenia are still obscure and are likely to be related to more general phenomena affecting the host rather than to direct damage of platelets or precursor cells by parasitism. Anemia and leukopenia are also present in T. cruzi infected mice.

Immunoregulation in human Schistosomiasis by idiotypic interactions and lymphokine-mediated mechanisms

Anti-idiotypic (anti-Id) T cells from schistosomiasis patients or former patients proliferate upon exposure to polyclonal or monoclonal anti-soluble egg antigen (SEA) antibodies. Chloroquine does not inhibit, the response, which is induced by F(ab')2 (but not soluble Fab) fragments of these antibodies. Purified T cells from former patients require macrophages or exogenous IL-1 to respond to anti-SEA Ids and can respond to matrix-bound Fab fragments in the presence of IL-1. These anti-Id T cells recognize the Ids directly. Chronic schistosomiasis patients immunoregulate the production of a non-IL-2 lymphokine that stimulates IL-2 receptor expression on resting T cells. This regulation is reversed upon chemotherapeutic cure.

Prospects for a nonliving vaccine against Schistosomiasis based on cell-mediated immune resistance mechanisms

We have designed a vaccine model based on induction of cell-mediated immunity and shown that it protects mice against Schistosoma mansoni infection. Mice are immunized by intradermal injection with schistosome antigens plus BCG. Resistance is dependent on the route of antigen presentation and the adjuvant chosen. The pattern of resistance correlates with sensitization of T lymphocytes for production of gamma interferon, a macrophage activating lymphokine that stimulates the cellular effector mechanism of protection. Purified schistosome paramyosin, a muscle cell component present in soluble parasite antigenic preparations, is immunogenic for T lymphocytes and induces resistance when given intradermally with BCG. It is likely that this protein, and possibly other soluble molecules that are released by the parasites of a challenge infection, induce a cellular inflammatory response resulting in larval trapping and/or killing by activated macrophages. These results verify the feasibility of a vaccine against schistosomiasis based on induction of cell-mediated immune resistance mechanisms.

Schistosoma mansoni: structural damage after treatment with oxamniquine

The effects of a single dose (100 mg/kg-body weight of mouse) of oxamniquine on the worm's tegument and paranchyma in relation to the process of immunological granulomatous reaction of the host's liver are described under light and electron microscopy (EM). The lesions caused by the drug are sequentially and simultaneously described in form of swelling, surface bulble and disruption with erosions. Ulceration in the tubercules with loss of spines is often more extensive and severe in male worms and concentration of host's mononuclear cells is observed. The possible role of host's immune response is discussed.

Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization

Malaria transmission-blocking immunity has been studied in natural malaria infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection of following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent.

Molecular mechanisms and biological importance of Plasmodium falciparum erythrocyte rosetting

Rosetting, i.e. the spontaneous binding of uninfected to malaria infected erythrocytes and endothelial cytoadherence may hinder the blood flow and lead to serve Plasmodium falciparum malaria. Falciparum isolates obtained from unconscious patients all form rosettes and/or express a significantly higher man rosetting rate than isolates from patients with uncomplicated malaria. Furthermore, sera of patients with cerebral malaria are devoid of anti-rosetting activity while sera from patients with mild disease carry high levels of anti-rosetting antibodies. The presence of anti-rosetting antibodies also seems important for the efficient interaction of rosetting infected rbc and leucocytes. Two parasite derived rosetting ligands of Mr 22k and Mr28K named "rosettins, have been found on the surface of rosetting infected erythrocytes. CD36 has in at least some strains of parasites been found to function as a rosetting receptor on the uninfectederythrocyte. Heparin disrupts rosettes of P. falciparum in vitro and inhibits the sequestration of rosetting cells ex vivo. In conclusion, rosetting seems a crucial factor in the development of cerebral malaria and treatment of patients with anti-rosetting substances might become an effectivew adjunct in the treatment of severe malaria.

Mechanisms of protective immunity against asexual blood stages of Plasmodium falciparum in the experimental host Saimiri

In the Saimiri monkey, an experimental host for human malaria, acquired protection against Plasmodium falciparum blood stages depends on the IgG antibody populations developed. In vivo protective anti-falciparum activity of IgG antibodies is correlated with the in vivo opsonizing activity promoting phagocytosis of parasited red bloood cells. In contrast, non protective antibodies inhibit this mechanism by competing at the target level. A similar phenomenon can be and human infection. Anti-cytoadherent and anti-rosette antibodies developed by Saimiri and humans prevent the development of physiopathological events like cerebral malaria which can also occur in this experimental host. Furthermore, transfer to protective human anti-falciparum IgG antibodies into infected Saimiri monkeys exerts an anti parasite activity as efficient as that observed when it is transfered into acute falciparum malaria patients, making the Saimiri an even more attractive host. Studies on the role of immunocompetent cells in the protective immune reponse are still in their infancy, however the existance of a restricted polymorphism of MHC II class molecules in the Saimiri confers additional theoretical and practical importance to this model.

Effector functions of eosinophils in schistosomiasis

The dual function of eosinophils is clearly illustred in schistosomiasis. Well equipped in membrane receptors for immunoglobulins and complement, and due to the presence of granule basic proteins, eosinophils can become cytotoxic for parasite larvae and thus participate to protective immunity. However mediators can also exert their cytolytic effect on normal cells or tissues, inducing therefore pathology. Through ADCC mechanisms against schistosome larvae in vitro involving different antibody isotypes (IgG, IgE and IgA) and also in experiments performed in vivo, eosinophils have been clearly involved in protective immunity. Although no direct evidence of the protective role of eosinophils were brought in humans, the striking association of eosinophil-dependent cytotoxic antibody isotypes with resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, strongly, suggested the participation of eosinophils in antibody-dependent protective immune response. However eosinophils could also participate to granuloma formation around S. mansoni eggs and consequently to the pathological reactions induced by schistosomiasis.

Immunoregulatory mechanisms and Chagas' disease

During the course of experimental Chagas' disease, several immune disorders occur. In the acute phase, T and B cell plyclonal activation is associated to immunossupression. At the chronic stage. T cells - of the TH2 subset - participate to the pathology characteristic of Chagas'disease. Data obtained after infection of BALB/Xid mice suggest that polyclonal activation may be dependent on B1 (CD5) cell activation. Moreover, these mice fail to develop the pathological features of the chronic infection. Control of lymphokine secretion might play a key role in the clinical status of Chagas'disease.

Mechanisms of immune protection in the asexual blood stage infection by Plasmodium falciparum: analysis by in vitro and ex-vivo assays

Mechanisms of immune protection against the asexual blood stage infection by Plasmodium falciparum are reviewed. Recent studies of two independent lines of research developed at the Institute Pasteur, in humans and primate infections clearly indicate an obligatory interaction of antibodies and effector cells to express the anti-parasitic effect.

Ultrastructural study on experimental infection of rotavirus in a murine heterologous model

Viral replication, histopathological and ultrastructural changes were observed for a period of nine days in the small intestine of suckling mice infected with a simian rotavirus (SA11). Samples taken from duodenum, jejunun and ileum were prepared for light microscopy, transmission and scanning electron microscopy analysis. Histopathologic effect could be detected within 8 hr post-infection, when only a few altered cells were observed. Damage was extensive after 16 hr post-infection, showing swollen enterocytes and reduced and irregularly oriented microvilli at intestinal villi tips. Virus particles were detected at 16 and 48 hr post-infection, budding from the viroplasm into the rough endoplasmic reticulum cisternae in ileum enterocytes. Clear evidence of viral replication, observed by electron microscopy was not described before in heterologous murine models. Regeneration of the intestinal villi began at the third day post-infection. Despite some differences observed in clinical symptoms and microscopic analysis of homologous and heterologous rotavirus infections, we concluded that mechanisms of heterologous rotavirus infection in mice follow similar patterns to those observed in the homologous models.