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Roles of antigen presenting cells in regulation of Th17 response against Candida albicans
Böhmová, Helena ; Dobeš, Jan (advisor) ; Kostovčíková, Klára (referee)
Candida albicans is a common human pathobiont that inhabits mucosal surfaces throughout the body. In healthy individuals, it behaves as a benign member of the microfora. However, in immunocompromised individuals Candida becomes pathogenic and causes extensive mucosal infections. In the most severe cases, Candida translocates into the bloodstream and causes life-threatening deep tissue infections. Although the innate immune components involved in early anti-Candida immune response are relatively well defned, our knowledge regarding adaptive T cell responses to Candida is limited. Several populations of antigen-presenting cells (APCs) have been implicated in the induction of protective Th17 response against Candida - including innate lymphoid cells type 3 (ILC3s), conventional dendritic cells (cDCs) and CX3CR1+ mononuclear phagocytes (MNPs). The cellular and molecular mechanisms by which Candida-specifc T cells are induced have not yet completely been identifed. Presented thesis focuses on the involvement of direct antigen presentation by these APC populations in mounting the anti-Candida adaptive immune response. Furthermore, this is investigated in the context of both gastrointestinal colonization and bloodstream infection by C. albicans. In the frst part, published data concerning the immune...
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Modulation of the STING signaling pathway
Vaneková, Lenka ; Veverka, Václav (advisor) ; Hirsch, Ivan (referee) ; Dobeš, Jan (referee)
cGAS-STING signalling pathway plays the key role in the host immune defence in diverse pathologies including, autoimmune and autoinflammatory diseases, cancer, senescence and ageing, pathogen infection, i.e., bacterial, viral infection, such as hepatitis B (HBV). HBV infection can result in either an acute or a chronic type (CHB), both of wide range of immune invading mechanism potentially leading to liver cirrhosis, steatosis, or hepatocellular carcinoma. Currently, two available CHB therapies are approved, both of which rarely result in the complete cure and often require life-long application. The development and validation of novel CHB therapeutics relies on suitable CHB animal models. The main goal of this thesis was to develop a mouse model reflecting CHB based on hydrodynamic injection suitable for robust preclinical testing of novel CHB therapeutics. Two delivery systems were compared, adeno-associated plasmid vector (pAAV) and minicircle construct, encoding HBV genomes of two genotypes (A or D) with introduced point mutation in the START codon of the polymerase in two immunocompetent mouse strains, C57Bl/6 and C3H/HeN. Persisting expression of viral antigens was observed only in the C3H/HeN mice when using pAAV construct encoding HBV genome of genotype A with introduced T2308C point...
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Fungal Microbiota and Inflammatory Bowel Disease
Vančíková, Sabína ; Kostovčíková, Klára (advisor) ; Dobeš, Jan (referee)
Inflammatory bowel disease (IBD) is a term for the gastrointestinal tract's chronic inflammatory disorders, evincing growing worldwide prevalence. Commonly, IBD is divided into two major subgroups, Crohn's disease (CD) and ulcerative colitis (UC). Despite intensive efforts, IBD etiology and development mechanisms are not fully understood. Gut barrier dysfunction, dysbiosis, and overreactive immune response to gut microbiota appear to have a significant impact. While bacteria are the most studied gut inhabitants, research on the role of fungal microbiota (mycobiota) in IBD lags behind. This diploma thesis aimed to study immune responses to gut mycobiota in IBD. Levels of antifungal antibodies against gut residents and biomarkers relevant to gut barrier damage and microbial translocation were measured in the sera of IBD patients and healthy individuals. Sera of individuals diagnosed with UC, CD, and IBD associated with primary sclerosing cholangitis (PSC-IBD) were used. Since continuous intestinal macrophage activation is a feature of IBD, the effect of selected fungal mycobiota species on the reactivity of peripheral blood-derived macrophages from healthy donors was assessed in vitro. The levels of serum antibodies against mycobiota components were higher in IBD patients than in controls, and the...
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Induction of immune responses by intestinal segmented filamentous bacteria
Pacáková, Iva ; Dobeš, Jan (advisor) ; Schwarzer, Martin (referee)
The intestine is constantly exposed to a variety of pathogens, and therefore a proper function of the intestinal barrier is essential for the overall health of the body. Segmented filamentous bacteria are members of the gut microbiota residing in the terminal ileum of the small intestine, where they penetrate through the mucus layer and tightly associate with intestinal epithelial cells. This SFB association with the epithelium is accompanied by the formation of endocytic vesicles filled with an antigen that triggers the IgA production in the intestine and the Th17 cell dependent immune response. There are two steps for the induction of Th17 cells. First, SFB-dependent induction of Th17 cells requires antigen presentation by MHC class II molecules. Therefore, antigen-presenting cells migrate to the site of induction in mesenteric lymph nodes and prime antigen-specific naive T cells to become RORγt+ pre-Th17 T cells. Secondly, activated T cells migrate back to the lamina propria, where they undergo functional maturation by triggering cytokine production. As a result, Th17 cells accumulate in lamina propria, where they produce their effector cytokines IL-17 and IL-22, further affecting the gut's overall balance. However, the extensive Th17 polarization induced by SFB may subsequently contribute to...
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Significance of the major histocompatibility complex for hemopoietic stem cell transplantation
Graman, Vojtěch ; Slavčev, Antonij (advisor) ; Dobeš, Jan (referee)
The genes of the major histocompatibility complex are located on the short arm of chromosome 6 and encode surface glycoproteins (HLA glycoproteins), which ensure the presentation of self and foreign peptides on the cell surface. These glycoproteins are subsequently recognized by T-lymphocytes and by other cells of the immune system. When the HLA-peptide complex is recognized as foreign, T-lymphocytes and other components of the immune system are activated, and the foreign cell is destroyed. Therefore, in hematopoietic stem cell transplantation (HSCT), HLA incompatibility between donor and recipient causes a strong immune response against the transplanted cells, and is therefore a major criterion in selecting suitable stem cell donors. This work briefly summarizes the current knowledge about the structure and function of HLA class I and class II antigens. The work focuses on HLA typing techniques to help understand the HLA system, which include serological typing methods, as well as modern molecular typing methods based on PCR and next-generation sequencing, and their relevance for HSCT. We also focus on HSCT processes and preparatory therapy, but the main emphasis is on the importance of HLA incompatibilities between stem cell recipients and donors and their effect on HSCT outcome.
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The sphere of an enterprise and the firm agenda in České Budějovice area along 1850-1950 years
Plávek, Aleš František ; Ebelová, Ivana (advisor) ; Dobeš, Jan (referee)
This diploma work has for its object an existence of enterprise in the České Budějovice area a Eormation of professional constitutionalism in half of 19th century during an introduction oE the new civil and criminal judicial system in 1895 - 1896 years and declaration of republic until the disapperance oE trades and nationalization in 1950 year. Diplomatic part oE this work occupies itselE with office agenda arising from the relations between offices and tradesmen or their firms. It has a respect with regard to very high quantity of written material, above aU to two institutions, namely Regional Commercial Lawcourt and also the Chember of Commerce and Industry; both with headquartes in České Budějovice. The last part refers to usmg of legalising means, also the seals and stamps in diplomatic contact oE trade associations with state or professional offices, mainly with the commercial lawcourt. This short sigillographic excursion does its best to map two halfcenturies.
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Private business restrictions throught organisational changes in the heavy-machinery industry structure (ČKD, national enterprise and its role in struggle for confiscated industry property)
Stříteský, Hynek ; Šouša, Jiří (advisor) ; Dobeš, Jan (referee)
Po druhé světové válce došlo ve světě k zásadním mocenskopolitickým změnám a společnost řady zemí zaznamenala výrazný myšlenkový posun doleva, což se odrazilo v jejich hospodářské politice zejména podstatným zvýšením role státu. Posílení Sovětského svazu a vznik lidově demokratických republik pak vyústili v bipolární rozdělení světa na Východ - Západ. Poválečná československá společnost, traumatizovaná vzpomínkami na velkou hospodářskou krizi a události následující po září 1938, zaznamenala výraznou radikalizaci a podstatně v ní zesílilo levicové smýšlení. Požadavek širokých společenských změn, jež by zabránily opakování předválečného vývoj e vedoucího k rozbi tí republiky, se setkával s širokou veřejnou podporou, i když samozřejmě existovaly rozdílné názory na jeho realizaci. Mezi pro středky, kterými byl utvářen hospodářský a sociální systém obnovené republiky, patřilo vedle důsledného provedení pozemkové reformy, plánování či přeorientování partnerských vztahů na Sovětský svaz také znárodnění velkého a klíčového průmyslu 1 a konfiskace maj etku Němců, Mad'arů, zrádců a kolaborantů. V podstatě se jednalo o řadu opatření, jež měla přetvořit stávající uspořádání společnosti. Nový sociální řád se obhajoval potřebou povznést široké vrstvy obyvatelstva.
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Adolf Ludvík Krejčík. Edition of memories
Kuprová, Renata ; Dobeš, Jan (advisor) ; Kahuda, Jan (referee)
The aim of this bachelor thesis is to fully retrieve the first part of the manuscript memoires of noted Czech archivist and historian PhDr. Adolf Ludvík Krejčík (1877 - 1958). The manuscript was preserved as a part of his personal papers, which is now located in the National Archive of Czech Republic in Prague. Even though the title of the first part is "From the Birth until 1948" the author describes events only up to the beginning of the 20-th century. The author narrates his childhood and juvenile age, his study at the Faculty of Philosophy of the Charles Univresity in Prague and at the prestigeous Institut für österreichische Geschichtsforschung in Vienna, his scientific work at the Austrian Historical Institute in Rome and his activity in the Schwarzenberg Archive in Třeboň and Moravian Land Archive in Brno. While writing his memoires, Krejčík regrettably did not cover the period during which he founded the Czechoslovak State Agricultural Archive, where he served as its first director. In this period was Krejčík counted amongst the most prominent Czech archivists. Far from being centered around his scientific activities, the memoires cover broad area of authors cultural interests (especially music and theatre) and the circumstances of everyday life, as well as other subjects. The editional work was...
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