In vitro interactions of human blood and intestinal intraepithelial lymphocytes with Cryptosporidium parvum and C. parvum permissive enterocytic cell lines.
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Biomedical subjects
Publications and source records attributed to J J Ballet.
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In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weight ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection, in parallel to the parasitaemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced) stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced) triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that the polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.
Human antibody response to Cryptosporidium parvum has been previously shown as involving immunoglobulin (Ig)M and IgG isotypes. The interest in anti-cryptosporidial IgA antibody response has been recently stimulated by studies on the therapeutic effects of secretory IgA antibodies to Cryptosporidium in animal models and in patients. In the present study, isotypes of serum anti-Cryptosporidium antibodies have been characterized in donors of the following categories: (a) healthy adults, (b) healthy children, (c) immunocompetent children with transient cryptosporidial diarrhea, (d) HIV-infected patients without clinical and parasitological evidence of Cryptosporidium infection and (e) AIDS patients with cryptosporidial diarrhea. Antibodies were detected using C. parvum oocysts purified by density gradient centrifugation from bovine faeces. The IgA antibodies were revealed using alpha-chain specific antibodies. Indirect immunofluorescence analysis with oocysts was used as control. Although high levels of serum antibodies of the IgA class were detected in some donors in the group of healthy adults, elevated values were consistently found in HIV-infected patients. Higher values were found in HIV patients with clinical cryptosporidiosis. The presence of a secretory component in serum IgA antibodies in these patients has been documented. Data indicate that IgA serum antibodies are produced as well as IgM and IgG antibodies upon contact with the parasite, and suggest that elevated IgA serum antibodies to Cryptosporidium are not associated with protection in HIV patients.
Cryptosporidium parvum, a coccidian parasite can cause mild or severe self-limiting diarrhea in immunocompetent humans, but chronic and life-threatening in immunocompromised individuals. An immunosuppressed rat model with persistent cryptosporidiosis was used to investigate the anti-cryptosporidial activity of drugs. Using curative procedures, no activity was found with 6 antibiotics assayed, including spiramycin (31-100%). Mepacrine at a dose of 100 mg/kg had mild activity (19%), while lasalocid (10 mg/kg) and sulfadimethoxine (60 mg/kg) exhibited a 0.1% and 13%, activity respectively. This experimental immuno-suppressed rat model appears suitable for screening candidate drugs either for preventive or curative treatment of cryptosporidiosis.
The occurence of hypercalcemia appears to be unusual in leukemia. The mechanisms are numerous: secretion of PTH of PTH like substance, prostaglandin E2 or vitamin D like sterols. The reported case is one of lymphoblastic acute leukemia and hypercalcemia associated with osteoclast activating factor secreted by leukemic cells. In this patient the serum levels calcium closely paralleled the course of acute leukemia.
Methisoprinol (Isoprinosine), a purine derivative, has been shown to exert a number of immunopharmacological effects, both in vitro and in vivo, in animal and human studies. The agent, somehow mimicking the effects of thymic factors, induces the appearance of phenotypic markers of differentiation on immature precursor T cells; enhances the proliferative response of murine and human lymphocytes to mitogens or antigens, augments helper or suppressor T cell functions and increases the production of lymphotoxin a lymphokine. It has also been shown that this drug can potentiate the effects of macrophage activating factor to stimulate macrophage, and of interferon to protect mice against experimental viral and tumor challenges. In humans, beneficial results have been reported from clinical trials testing the effects of methisoprinol in a variety of diseases including subacute sclerosing panencephalitis (SSPE), acute viral encephalitis, recurrent mucocutaneous infections due to type I and II Herpes viruses as well as in immune restoration of cancer patients with immunodepression following radiotherapy. The drug is also being studied in immunopathological disorders such as rheumatoid arthritis, systemic lupus erythematosus. Sjogren's disease and type A hepatitis. The large spectrum of effects of methisoprinol on a number of immune parameters, the increasing evidence of its therapeutic value in several pathological conditions and its safety of use qualifies this drug as an interesting immunoregulating agent.
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