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Vaccines against leishmaniasis
Krylová, Anna ; Spitzová, Tatiana (advisor) ; Leštinová, Tereza (referee)
Leishmaniasis is one of the world's neglected tropical diseases which is caused by protozoan parasites of the genus Leishmania. Proven vectors belong to two species of dipteran insect - Phlebotomus in the Old World and Lutzomyia in the New World. Over one billion people are at risk in endemic areas. Currently the mean to treat and control leishmaniasis is by vector control and drug treatment, mainly chemotherapeutic, which is linked to severe side effects and has poor efficiency. No prophylactic human vaccine is currently available but several dog vaccines are. However, plenty of vaccines have been intensively tested for human use. Some of them have achieved good results in clinical trials and are promising vaccine candidates. In this bachelor thesis I overview the newest research on vaccines against leishmaniases and report on several vaccine approaches. key words: leishmaniasis, vaccine, Leishmania, clinical trials, live attenuated vaccine, DNA vaccine, recombinant vaccine, salivary proteins
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The role of nitric oxide in helminthoses
Šmídová, Barbora ; Macháček, Tomáš (advisor) ; Leštinová, Tereza (referee)
Nitric oxide (NO) is a small gaseous molecule produced mainly by activated macrophages, but some other cells as well, in reaction to an infection. Since late 80s, when the effect of NO on schistosomes was demonstrated, many experiments have been conducted examining both the effect of NO on other helminths and its role in helminthoses. In vitro experiments center mainly upon direct effects of NO on helminths - loss of motility and viability in particular. On the other hand, in vivo studies focus on the course of infection and pathological changes in hosts. However, in vitro and in vivo data do not always corroborate. Moreover, the effects of NO differ not only across helminth genera but also for developmental stages of the same parasite.
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Attachment of trypanosomatids in the insect vector.
Tichá, Lucie ; Myšková, Jitka (advisor) ; Leštinová, Tereza (referee)
Trypanosomatids are protozoan parasites known for its medical and economical significance. Leishmania, Trypanosoma, Endotrypanum and Phytomonas genera are dixenous parasites. Part of the life cycle takes place in the insect vector, where the parasites are attached using their flagella. Supraplyarian Leishmania differs in the binding method depending on the type of vector it uses for its transmission. The attachment is dependent on lipophosphoglycan (LPG) in a specific vector while in a permissive vector, the interaction is based on a different mechanism (LPG-independent). Attachment of T. cruzi in the posterior part of a digestive system of a hemipterous bugs appears to be necessary for metacyclogenesis. Similar strategy seems to be used by T. brucei which is attached in the salivary glands. The genera Endotrypanum and Phytomonas are not medically significant pathogens, thus their life cycles have not been profoundly researched. Endotrypanum, as well as Leishmania, develops in the digestive system of sand flies, thus the binding mechanism could be analogous. Phytomonas develops in the salivary glands of hemipterous bugs which denotes similarity with T. brucei. Based on the collected data, it is assumed that the binding mechanism of the Trypanosmonatids is generally based on the lectin-like protein...
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Surface glycoconjugates of Leishmania parasites and their interactions with immune system of vertebrate host
Pacáková, Lenka ; Leštinová, Tereza (advisor) ; Kolářová, Iva (referee)
musí po vstupu do obratlovčího hostitele čelit obranným mechanismům hostitelské imunity a proniknout do cílové buňky - pokračuje. Evoluční strategií leishmanií vyvinutou k přelstění imunitního systému Mezi nejvýznamnější povrchové glykokonjugáty patří membránově vázané proteofosfoglykany a metaloproteáz lním účinkům produktů neutrofilů a zprostředk vazbu na makrofágy. Intracelulárně pak modulují signalizační dráhy, které vedou k produkci cytokinů, směřujících polarizaci imunitní odpovědi ve prospěch Th2. Výsledkem tohoto přesměrování je vyhnutí se účinkům toxického NO, čímž je ustanovena chronicita infekce. Glykokonjugáty jsou zkoumány jako účinná složka chránících obratlovce před nákazou či bránících zpětnému přenosu čímž dalšímu šíření infekce. Klíčová slova: leishmanie, lipofosfoglykan, glykoinositolfosfolipid, proteofosfoglykan, gp63, imunitní odpověď, makrofág
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Cellular and humoral host immune response to sand fly saliva
Leštinová, Tereza ; Kolářová, Iva (advisor) ; Kopecký, Jan (referee) ; Teixeira, Clarissa Romero (referee)
Sand flies (Diptera: Phlebotominae) are bloodfeeding insects serving as vectors of Leishmania parasites (Kinetoplastida). Sand flies possess salivary glands with pharmacologically active molecules that provide them with an effective weapon against the host defence and that play an important role in Leishmania infection development. During the bloodfeeding, sand fly saliva is inoculated into the feeding site. Repeated exposures induce saliva-specific immune response, both humoral and cell-mediated. While anti-saliva antibody response correlates with the intensity of exposure and can be used as a marker of exposure, specific cellular immunity provide protection against leishmaniasis in some vector-parasite- host combinations. Sand flies differ in composition of the saliva and thus the elicited immunity is species-specific. This species-specific variability makes difficult the development of one saliva-based vaccine applicable to different Leishmania-vector combinations. However, saliva composition is more conserved among closely-related vector species, which may evoke cross-protection in bitten and subsequently infected hosts. We focused on cross-reactive properties of saliva from Phlebotomus papatasi and Phlebotomus duboscqi, the two natural vectors of Leishmania major. We demonstrated that...
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Modulation of murine immune reactions by selected helminths
Pavlíková, Veronika ; Chanová, Marta (advisor) ; Leštinová, Tereza (referee)
Currently, the use of helminths in alternative treatment of immune mediated diseases is an attractive topic. Their therapeutic potential is justified by the ability to modulate the host immune system. To test this potential, we chose the flukes of Schistosoma mansoni, which is known to immunomodulate its hosts significantly, however also act as a strong pathogen. Due to high pathogenicity of classical infections we tried to compare its immunomodulation efficiency with alternative interactions of S. mansoni with the host. We tested a low-dose infection, nonproductive infection, immune stimulation with living or dead eggs (antigens) and restimulation by both, living and dead eggs. Stimulation with eggs was, for the short term, most effective in suppressing inflammatory immune response. From the long term point of view, low-dose infections. were most effective. Use of egg antigens has affected the immune system very poorly and nonproductive infection had no effect at all. Induction of experimental colitis and differences in the subsequent development in various models partially confirm our findings.
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Cytokines and chemokines, their role in the infections with helminths.
Majer, Martin ; Panská, Lucie (advisor) ; Leštinová, Tereza (referee)
Parasitic helminths belong to extracellular pathogens of mammals, including human. Immunologic response depends on their migration and site of dwelling within host body. The response is among other affected by cytokines and chemokines. These small proteins are responsible for appropriate proliferation and migration of other components of immune system. These bachelor thesis summarizes current knowledge about their role during helminth infection in mammals.
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Cellular and humoral host immune response to sand fly saliva
Leštinová, Tereza
Sand flies (Diptera: Phlebotominae) are bloodfeeding insects serving as vectors of Leishmania parasites (Kinetoplastida). Sand flies possess salivary glands with pharmacologically active molecules that provide them with an effective weapon against the host defence and that play an important role in Leishmania infection development. During the bloodfeeding, sand fly saliva is inoculated into the feeding site. Repeated exposures induce saliva-specific immune response, both humoral and cell-mediated. While anti-saliva antibody response correlates with the intensity of exposure and can be used as a marker of exposure, specific cellular immunity provide protection against leishmaniasis in some vector-parasite- host combinations. Sand flies differ in composition of the saliva and thus the elicited immunity is species-specific. This species-specific variability makes difficult the development of one saliva-based vaccine applicable to different Leishmania-vector combinations. However, saliva composition is more conserved among closely-related vector species, which may evoke cross-protection in bitten and subsequently infected hosts. We focused on cross-reactive properties of saliva from Phlebotomus papatasi and Phlebotomus duboscqi, the two natural vectors of Leishmania major. We demonstrated that...
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