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Macrophages in leishmania - sand fly - host interaction
Kratochvílová, Tereza ; Kolářová, Iva (advisor) ; Fialová, Anna (referee)
Sand flies (order Diptera) are vectors of Leishmania parasites (Trypanosomatida), which are inoculated into the host skin together with the vector saliva. Sand fly saliva plays the important role in the Leishmania transmission; in naive host it supresses the host immune response assisting Leishmania to establish the infection, while in repeatedly bitten host it elicits a protective immune response. The submitted thesis focuses on the effect of sand fly saliva on macrophages, the key cells in the infection control. In the first part of the thesis we established a laboratory model L. major - P. papatasi - Balb/c to describe the protective effect of saliva immunization on Leishmania infection development. Immunized mice were protected against Leishmania infection which was reflected in the ear lesion size, parasite load in the ear dermis and draining lymph nodes but also in cytokine production. On the contrary, produced lower amount of nitric oxide, while arginase activity was comparable with nonimmunized group. The IgG antibodies against saliva served as a marker of exposure to sandflies while IgG antibodies against Leishmania antigens served as a marker of infection severity. The experiments were aimed on the possibility of cross-protectivity in Balb/c mice against L. major between closely related...
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Targeted cancer therapy based on altered metabolism of amino acids
Šafrhansová, Lucie ; Starková, Júlia (advisor) ; Zelenka, Jaroslav (referee)
The effects of targeted therapies in the treatment of cancer have been extensively researched and tested in many clinical trials. In contrast to conventional chemotherapy treatment, targeted therapy should act specifically on cancer cells with limited toxicity and lower risk of side effects. One type of targeted therapy exploits the Achilles heel of cancer - the specificity of tumour metabolism. With knowledge of the metabolic differences between tumor and normal cells, we can set up conditions that normal cells easily bridge, while tumor cells die as a result. This can be achieved by removing certain amino acids from the extracellular environment on which cancer cells depend. A well-known enzyme that has been used therapeutically for many years is asparaginase. However, asparaginase therapy is only successful in some cancers, so further development is needed, as well as the search for enzymes with similar effects. Over the years, four other enzymes that could become an integral part of the treatment of cancer patients in the future have been discovered - arginine deiminase, arginase, methioninase and cyst(e)inase. Past and current studies have investigated their effects on cancer cells in vitro and in vivo. Successful elimination of cancer cells often comes with limitations as immunogenicity and...
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Macrophages in leishmania - sand fly - host interaction
Kratochvílová, Tereza ; Kolářová, Iva (advisor) ; Fialová, Anna (referee)
Sand flies (order Diptera) are vectors of Leishmania parasites (Trypanosomatida), which are inoculated into the host skin together with the vector saliva. Sand fly saliva plays the important role in the Leishmania transmission; in naive host it supresses the host immune response assisting Leishmania to establish the infection, while in repeatedly bitten host it elicits a protective immune response. The submitted thesis focuses on the effect of sand fly saliva on macrophages, the key cells in the infection control. In the first part of the thesis we established a laboratory model L. major - P. papatasi - Balb/c to describe the protective effect of saliva immunization on Leishmania infection development. Immunized mice were protected against Leishmania infection which was reflected in the ear lesion size, parasite load in the ear dermis and draining lymph nodes but also in cytokine production. On the contrary, produced lower amount of nitric oxide, while arginase activity was comparable with nonimmunized group. The IgG antibodies against saliva served as a marker of exposure to sandflies while IgG antibodies against Leishmania antigens served as a marker of infection severity. The experiments were aimed on the possibility of cross-protectivity in Balb/c mice against L. major between closely related...
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