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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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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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Structural characterisation of Prp45 and its interaction partners
Kulhánková, Lucie ; Novotný, Marian (advisor) ; Kostovčíková, Klára (referee)
Prp45 is a SNW protein that is part of a spliceosome and therefore participates in splicing of pre-mRNA into mRNA. In spliceosome Prp45 joins as part of NTC complex before splicing reactions. Prp45 has several known interactional partners (such as small subunit of U2AF, Cyp2, Prp5, Prp22, Clf1 and Cwc3). These proteins serve many functions in the spliceosome from stability to regulation of splicing reactions. Spliceosome consists of several dozens of proteins and several RNA and undergoes massive structural changes during executing its function. Until recently very little was known about the spliceosome structure; however, recent studies allow us to look at interaction network of this machine. In this work we focused on identification of both previously predicted and new interactional partners of Prp45. Using available spliceosome structures we aimed to describe these proteins structurally and functionally. Key words: splicing, Prp45, 3D struktura, spliceosome, binding partners
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Gut microbiota effect on neuropsychiatric diseases
Pospíšil, Vít ; Kostovčíková, Klára (advisor) ; Červená, Kateřina (referee)
The intestinal microbiome is formed by trillions of microorganisms that accompany us throughout our lives. Commensal gut microorganisms, as a complex system, interfere with diet processing and subsequent spectrum of released metabolites, which are involved in communication with other systems of the human body. Recently, a link between intestinal microbiota dysbiosis and activation of the immune response has begun to emerge. This pathophysiological condition is associated with the loosening of the tight junctions of the gut epithelial barrier, which could together with prolonged immune inflammation lead to what is known as irritable bowel syndrome. This disease is not only related to symptoms associated with bowel discomfort, but also to effects on afferent nerve endings. This connection has been called as the gut-brain axis and became the link between the gut microbiota and psychiatric diseases. This work is summing up the actual knowledge on this topic and offers a comprehensive overview of the subject from both an immunological and a microbiological point of view. Key words: gut-brain axis, depression, anxiety, antibiotics, antidepressants, probiotics, IBS
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Structural characterisation of Prp45 and its interaction partners
Kulhánková, Lucie ; Novotný, Marian (advisor) ; Kostovčíková, Klára (referee)
Prp45 is a SNW protein that is part of a spliceosome and therefore participates in splicing of pre-mRNA into mRNA. In spliceosome Prp45 joins as part of NTC complex before splicing reactions. Prp45 has several known interactional partners (such as small subunit of U2AF, Cyp2, Prp5, Prp22, Clf1 and Cwc3). These proteins serve many functions in the spliceosome from stability to regulation of splicing reactions. Spliceosome consists of several dozens of proteins and several RNA and undergoes massive structural changes during executing its function. Until recently very little was known about the spliceosome structure; however, recent studies allow us to look at interaction network of this machine. In this work we focused on identification of both previously predicted and new interactional partners of Prp45. Using available spliceosome structures we aimed to describe these proteins structurally and functionally. Key words: splicing, Prp45, 3D struktura, spliceosome, binding partners
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Microbiota and inflammatory bowel diseases
Gajdárová, Zuzana ; Kostovčíková, Klára (advisor) ; Grobárová, Valéria (referee)
Inflammatory bowel diseases (IBD) are an autoimmune illnesses affecting gastrointestinal tract. The main types include ulcerative colitis and Crohn's disease. Recently, primary sclerosing cholangitis (PSC) has also been associated with IBD. PSC is a chronic liver disease associated with bile duct stenosis. The exact pathogenesis and etiology of these diseases is not clear, despite the great efforts of the scientific community. They are multifactorial diseases that are associated with dysbiosis of intestinal microbiota. Their diagnosis is based on for patients unpleasant endoscopic examinations and therefore the search for new serum biomarkers is needed and appreciated target of scientific interest. In the first part of diploma thesis, we focused on the reactivity of peripheral blood cells of IBD patients to 10 selected representatives of typical intestinal microbiota: Lactobacillus plantarum, Bifidobacterium adolescentis, Blautia coccoides, Roseburia intestinalis, Eubacterium rectale, Faecalibacterium prausnitzii, Ruminococcus flavefaciens, Bacteroides thetaiotaomicron, Prevotella ruminicola and Escherichia coli. Reactivity of CD, UC and PSC- IBD patients was increased after stimulation with Faecalibacterium, Lactobacillus and Prevotella. However, we got low percentage of cytokine-producing cells,...
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