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Salivary proteins of sand flies and the immune aspects of Leishmania transmission
Vlková, Michaela ; Volf, Petr (advisor) ; Schwarz, Alexandra (referee) ; Remoue, Franck (referee)
Sand flies serve as the vectors of leishmaniasis and their saliva was shown to affect the outcome of Leishmania infection by immunomodulation of the host. On the other hand, sand fly saliva contains a large scale of farmacologically active proteins that are strongly immunogenous for bitten hosts and specific anti-saliva immunity initiated by repeated sand fly feeding provides protection against Leishmania infection. Specific cell-mediated immunity was shown to be the core of the protectivity; however, our data suggests that the protective immunity has certain limitations. In mice bitten by sand flies for prolonged periods, we observed the desenzitization in term of abrogation of the protective immunity. Thus, we can speculate that the protective effect of immunity is linked solely with the short-term exposure. Nevertheless, our experiments showed that this aspect is also conditioned by the immediate infection after the protective short-term immunization. Taken together, it seems that these limitations may explain the circulation of leishmaniasis in endemic areas, even though humans and animals are frequently immunized by bites of uninfected sand flies. Repeated sand fly feeding on various hosts also promotes production of anti-saliva antibodies that reflect the intensity of exposure. We...
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Salivary proteins of sand flies and the immune aspects of Leishmania transmission
Kindlová, Michaela
Sand flies serve as the vectors of leishmaniasis and their saliva was shown to affect the outcome of Leishmania infection by immunomodulation of the host. On the other hand, sand fly saliva contains a large scale of farmacologically active proteins that are strongly immunogenous for bitten hosts and specific anti-saliva immunity initiated by repeated sand fly feeding provides protection against Leishmania infection. Specific cell-mediated immunity was shown to be the core of the protectivity; however, our data suggests that the protective immunity has certain limitations. In mice bitten by sand flies for prolonged periods, we observed the desenzitization in term of abrogation of the protective immunity. Thus, we can speculate that the protective effect of immunity is linked solely with the short-term exposure. Nevertheless, our experiments showed that this aspect is also conditioned by the immediate infection after the protective short-term immunization. Taken together, it seems that these limitations may explain the circulation of leishmaniasis in endemic areas, even though humans and animals are frequently immunized by bites of uninfected sand flies. Repeated sand fly feeding on various hosts also promotes production of anti-saliva antibodies that reflect the intensity of exposure. We...
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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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Phlebotomine saliva: the perspecives of application of some of their recombinantly produced proteins
Rožníčková, Lucie ; Zídková, Lenka (advisor) ; Štáfková, Jitka (referee)
Sandflies (Diptera: Phlebotominae) are the vectors of one of the most significant tropical diseases, leishmaniosis. Their saliva contains substances with antihemostatic, vasodilatory and immunomodulatory effect. These substances are of great significance in transmission of leishmaniosis, because of their ability to influence the host immune response. Naive host saliva modulate the immune system to such an extent, that it reduces an infective dose and increases the pathogenicity of leishmaniosis. On the other hand, a repeatedly exposed host generates a cellular and antibody immune response, which is able to make the initial development of infection impossible. Repeated exposure of individual sandflies lead to formation of antibodies against components of saliva, which may play a role as a rate exposure indicator and thus the risk of leashmaniosis infection. These proteins and glycoproteins can be produced by recombinant DNA technology. Recombinant vaccine could help in the fight against leishmaniasis. Keywords: saliva, sand fly, leishmania, recombinant proteins.
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Macrophages and nitric oxide in leishmania - sandfly - host interactions
Kratochvílová, Tereza ; Fialová, Anna (referee) ; Kolářová, Iva (advisor)
Leishmania reside fagolysosome of macrophages immediately after their entry to host where they multiply and consequently infect other macrophages or eventually other cells. A synthesis of a reactive reactant of oxygen and nitrogen is one of the mechanisms that some mammal cells are equipped with and that also contributes to eradication of leishmania. Nitric oxide rising during a metabolic change of L-arginine under the catalysis of NO synthase is of a large importance. Beyond cytotoxic function, nitric oxide is involved in signalling pathways for a neurotransmission (nNOS) and vasorelaxation (eNOS). Not all types of macrophages have ability to produce NO (iNOS). It is a heterogeneous group differing in immunological function and also in physiology. A group of classical activated macrophages represents an effective APC capable of efficient killing of intracellular pathogens. In addition to NO, they also secrete an inflammatory cytokines, which evolve an immune reaction towards to Th1. Contrary to this, a group of alternative activated macrophages is not capable of any efficient antigen presentation and nitric oxide production but produces L-ornithine, which is a precursor of polyamines, which leishmania utilizes for its own intracellular growth. For the mouse model, status of resistance and/or...
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