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Antigenome defines a selection of mutated tumor peptides driving tumor-specific T-cell response
Hadlová, Petra ; Drbal, Karel (advisor) ; Dibus, Michal (referee)
T cells, as an essential part of the adaptive immune system, play crucial role in eradication of tumor growth. T cells target, interact with and eventually annihilate the tumor cells in antigen- specific (Ag) manner. T cells interact with tumor cells via short epitopes bound to the major histocompatibility complex (MHC) molecules on the tumor cell surface. Tumor specific neoepitopes arise from random somatic mutations and constitute a part of the tumor antigenome. Antigenome comprises of two classes of antigens, tumor specific antigens (TSA) and tumor associated antigens (TAA). TSA are neoantigens carrying neoepitopes unique to each tumor. TAA are self-antigens presented by both tumor cells and non-transformed cells. Each tumor cell is able to develop numerous ways to evade the immune system consisting of T cells, NK cells, macrophages and other mechanisms employed. Despite that immunotherapy has shown a great potential in personalized medicine. The stratification of responsive patients is essential for effective and durable management of therapy in clinical practice. Methods are employed, which study existing reactive T cell clones, somatic mutations present in each patient, role of somatic mutations in tumor development and present neoepitopes. All these patient- specific features facilitate...
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Inflammatory Bowel Diseases in pregnancy
Kovářová, Tereza ; Krátká, Zuzana (advisor) ; Hadlová, Petra (referee)
(EN) Inflammatory bowel disease is a chronic autoimmune disease of the intestinal tract including Crohn's disease, ulcerative colitis, and other unspecified colitis. Depending on the type of disease, inflammation affects the small or large intestine or rectum. It is a multifactorial disease in which the intestinal microflora, the immune system status, and genetic predisposition are crucial. IBD is most often diagnosed in late adolescence or early adulthood. Due to the availability of quality treatment, the health status of IBD patients also improves, allowing them to consider starting a family after the disease has calmed down. Patients have fewer children than the general population, but there was no significantly higher risk of infertility. A prerequisite for successful pregnancy and childbirth is a stable condition of the disease and the use of treatment during pregnancy to prevent relapse. A specific problem of patients is voluntary childlessness because of worries about the worsening of IBD during or after pregnancy, about negative effects of treatment on a foetus, but also an occurrence of disease in offspring This work aims to summarize the issue of pregnancy in patients with IBD and to provide information on the current situation in patients with IBD in the Czech Republic. Keywords:...
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Cytometric assay of antigen-specific T cell response in monitoring of BCG vaccine therapy
Hadlová, Petra ; Drbal, Karel (advisor) ; Kalina, Tomáš (referee)
Bladder carcinoma (BCa) is among the most common carcinomas in the Western world. Despite the availability of effective therapies, there is currently an urgent need to develop a stratification method, which would enable the accurate identification of patients responsive to therapy. In the theoretical part of my diploma project I describe the heterogeneity of BCa and the currently applied immunotherapeutic approaches. I specifically focused on the Bacillus Calmette-Guérin (BCG) vaccine instillation. For decades another use of BCG has been a prophylactic vaccination against tuberculosis (TB) infection. BCG serves as a model treatment because it is highly efficient when prescribed to the responsive patient. However, an effective stratification is yet to be developed for BCa and latent tuberculosis infection (LTBI) diagnosis and/or monitoring. In the experimental part of my project, I developed and tested a 10-parameter panel for T cell- specific activation test (TAT) applicable for a stratification of BCa patients as well as for the detection of LTBI. I tested the panel on positive controls using flow cytometry (FCM) method because it allows for detection and measurement of dozens of markers at a single cell level. It is easily applicable to available urine and blood samples obtained from BCa...
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Antigenome defines a selection of mutated tumor peptides driving tumor-specific T-cell response
Hadlová, Petra ; Drbal, Karel (advisor) ; Dibus, Michal (referee)
T cells, as an essential part of the adaptive immune system, play crucial role in eradication of tumor growth. T cells target, interact with and eventually annihilate the tumor cells in antigen- specific (Ag) manner. T cells interact with tumor cells via short epitopes bound to the major histocompatibility complex (MHC) molecules on the tumor cell surface. Tumor specific neoepitopes arise from random somatic mutations and constitute a part of the tumor antigenome. Antigenome comprises of two classes of antigens, tumor specific antigens (TSA) and tumor associated antigens (TAA). TSA are neoantigens carrying neoepitopes unique to each tumor. TAA are self-antigens presented by both tumor cells and non-transformed cells. Each tumor cell is able to develop numerous ways to evade the immune system consisting of T cells, NK cells, macrophages and other mechanisms employed. Despite that immunotherapy has shown a great potential in personalized medicine. The stratification of responsive patients is essential for effective and durable management of therapy in clinical practice. Methods are employed, which study existing reactive T cell clones, somatic mutations present in each patient, role of somatic mutations in tumor development and present neoepitopes. All these patient- specific features facilitate...
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Chaim Potok's selected characers and their resistance towards assimilation
Hadlová, Petra ; Ulmanová, Hana (advisor) ; Veselá, Pavla (referee)
Thesis abstract in English The thesis analyzed the general tendency of American Jews and their descendents to resist assimilation with a much higher probability than the other immigrant groups present in the United States of America. The thesis approached the problematics through sociological, psychological and religious perspectives as well as through cultural studies and literature studies. The thesis established three major aspects of Judaism, on whose basis, it explored the reasons for the notable defiance to assimilation. These three were concluded to be: religious aspect of Judaism along with the significance of family and community, and the focus on both religious and secular education rooted in Judaism. The thesis reached the conclusion that the assimilation in the Jewish community is and will remain significantly slower and the changes will occur mainly in stringency of denomination and the gradual shift towards less orthodox forms of the religious practice. The thesis has been examined and proved based on two novels by an acclaimed orthodox Jewish writer Chaim Potok, which were selected to be The Chosen and My Name is Asher Lev. The thesis focused on the work of Chaim Potok because he is an exceptional writer appreciative of the Jewish heritage and culture and in his novels he pays tribute to...
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