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The Mechanism of Pathogenesis of Experimental Autoimmune Uveitis and Possilbilities of Their Regulation
Klímová, Aneta ; Heissigerová, Jarmila (advisor) ; Pitrová, Šárka (referee) ; Holáň, Vladimír (referee)
Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...
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Effect of gluten-free diet on potentially regulatory immune mechanisms in human type 1 diabetes
Císařová, Radka ; Funda, David (advisor) ; Zadražil, Zdeněk (referee)
Type 1 diabetes (T1D) is an autoimmune disease, whose incidence is rising every year, and its prevention or a cure does not exist. T1D is influenced by multiple genetic factors but environmental factors represent the major contributor to the recent almost epidemic increase of T1D incidence worldwide, primarily in developed countries. Amongst these factors belong for example enteroviral infections, microbiota dysbiosis or gluten-free diet (GFD). GFD has been proven to have a protective effect in NOD mice, which is a spontaneous model of T1D, and a beneficial effect on glycemic control in humans, when administered after T1D onset. This diploma thesis examined changes of regulatory and potentially regulatory T-cells and their cytokines in peripheral blood mononuclear cells (PBMC) of T1D children, who underwent 12-month intervention trial of GFD. Secondly, the thesis assessed if the influence of GFD on immune regulatory functions can be transferred by colonization of germ-free NOD mice with gut microbiota of these children. We have found that intervention with GFD increases percentage of Tr1 cells and IL-10 producing CD4+ T-cells in PBMC of T1D children. Furthermore, the beneficial effect on immune regulation can be at least partially transferred to NOD mice by the colonization with human microbiota...
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The Mechanism of Pathogenesis of Experimental Autoimmune Uveitis and Possilbilities of Their Regulation
Klímová, Aneta ; Heissigerová, Jarmila (advisor) ; Pitrová, Šárka (referee) ; Holáň, Vladimír (referee)
Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...
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