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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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The role of the immune system in colorectal and ovarian cancer
Kocián, Petr ; Hoch, Jiří (advisor) ; Prausová, Jana (referee) ; Žaloudík, Jan (referee)
Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome cansignificantly vary among patients within the same stage. Data collected from largecohorts of human cancers has demonstrated the impact of immune-classification, which has a prognostic value that may add largely to the significance of the AJCC/UICC TNM-classification. In our study we examined the immune cells that infiltrated the tumor tissues of colorectal and ovarian cancer patients. In a cohort of newly diagnosed colorectal cancer patients we examined the correlations between the KRAS mutational status, patterns of tumor-infiltrating immune cells and the presence of tumor recurrence. Our data suggest that colorectal cancer patients with low levels of tumor-infiltrating lymphocytes, a high CD1a/DC-LAMP tumor-infiltrating dendritic cells ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrence. In ovarian cancer patients we focused on the dynamics of the tumor-infiltrating...
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