National Repository of Grey Literature 39 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Diversity of CD8+ T-cell adaptive immune responses
Paprčková, Darina ; Štěpánek, Ondřej (advisor) ; Dobeš, Jan (referee) ; Gerrard, Audrey (referee)
CD8+ T cells are specialized immune cells that recognize and eliminate infected or malignant cells by directly attacking and destroying them. Moreover, their ability to form long-lasting memory responses ensures a rapid immune defense upon subsequent encounters with the same pathogens, making them indispensable for overall immune system function and maintaining health. Despite all of this, many aspects of their biology are still not well understood. The main objective of this thesis is to delve deeply into the adaptive immune responses of CD8+ T cells, focusing on elucidating several critical aspects. Firstly, we conducted a review and a research study of T-cell receptor (TCR) self-reactivity to understand its influence on immune responses. Intriguingly, experimental findings revealed that the degree of TCR self-reactivity did not impact the magnitude or type of the immune response. Instead, it played a decisive role in determining the fate commitment of CD8+ T cells in the periphery during homeostasis, shedding light on a nuanced regulatory mechanism. Another part of the research probed into per-cell differences of activated naïve and memory T cells. This investigation unveiled the remarkable potency of memory T cells to generate long- lived effector memory T cells. In contrast, naïve T cells...
Signaling pathways in T-cell-mediated immunity
Janušová, Šárka ; Štěpánek, Ondřej (advisor) ; Hons, Miroslav (referee) ; Abramson, Jakub (referee)
The immune system provides protection of the host against pathogens, and tumor cells while maintaining a tolerance to self-tissues. T cells are important players in orchestrating the immune response. Helper T cells navigate other cells in the course of the immune response, cytotoxic T cells directly kill infected or altered cells, and regulatory T cells suppress the overt activation of above mentioned. T cells are activated via their antigen-specific T-cell receptor (TCR), but for proper activation, they need additional signals from co-stimulatory or inhibitory receptors. This double-step activation is one of the regulatory steps to prevent aberrant T-cell activation. The main part of this thesis is focused on understanding of the signal propagation and regulation of the T-cell signaling. We used a tandem affinity purification followed by mass- spectrometry analysis to describe the composition of the receptor signaling complex of TNFR- SF members, GITR and OX40. We employed the same method to analyze the signalosome of IL-17R. One of the described components of all the receptors is ABIN1. We generated ABIN1 knock-out mice that exhibited signs of autoimmunity and its T cells were hyperresponsive to various stimulation in vitro and in vivo. We reported ABIN1 as a regulator ot T-cell signaling. In the...
The role of the interaction of LCK with CD4/CD8 coreceptors
Cesneková, Michaela ; Štěpánek, Ondřej (advisor) ; Černý, Jan (referee)
LCK kinase is an essential regulator of T-cell signalling that interacts with CD4 and CD8 coreceptors, which are crucial for T-cell development and T-cell lineage commitment. Their role, as well as the role of their interaction with LCK in the peripheral T cells, remains disputable, despite being studied for decades. This thesis aims to investigate the importance of LCK-coreceptor interaction in CD8+ T cell signalling and development and to determine the significance of the serine residues in LCK-mediated CD4 endocytosis. We used LCK variants bearing mutations of the coreceptor binding site or its catalytic domain in both mice and cell lines to solve this perplexity. First, the enzymatic activity of LCK variants was evaluated in this thesis. Second, we demonstrate that the function of CD8 is both, LCK-CD8 interaction dependent and independent. Then we examined the late stage of CD8+ T cell development, showing that the absence of the interaction has very mild consequences. It affects only the response of post- selection CD8 single-positive, but not double-positive, thymocytes to sub-optimal antigenic stimulation. Finally, we observed that CD4 with the mutation of all three intracellular serines to alanines shows similar LCK-dependency as wild type CD4. Overall, this study sheds light on the...
Characterization of a novel CD8+ T-cell subset with polyamine metabolism signature
Cimermanová, Veronika ; Štěpánek, Ondřej (advisor) ; Dobeš, Jan (referee)
CD8+ T cells play a crucial role in the adaptive immune response to combat infections and tumors. Previous research into T-cell heterogeneity has revealed that subsets of antigen- experienced CD8+ T cells possess different functional properties. However, the functional diversity might already be predetermined in their naïve steady-state precursors. Recently, the Lab of Adaptive Immunity discovered a new and rare murine steady-state CD8+ T-cell subset, known as Tpam cells (CD8+ T cells with polyamine metabolism signature). Since polyamine metabolism has been linked to T-cell activation and differentiation, studying this novel subset can provide new insight into the fate of CD8+ T cells upon TCR stimulation. This diploma thesis aimed to characterize Tpam cells in terms of their origin, steady-state phenotype, fate after TCR stimulation, and potential functional role. We took advantage of various mouse models to investigate the formation of Tpam cells and found that they are dependent on a diverse TCR repertoire and are presumably formed by low-grade TCR signaling. We executed an adoptive transfer into T-cell deficient mouse model to examine their steady-state phenotype and performed an ex vivo TCR-mediated activation assay to observe their fate after activation. Our findings show that Tpam cells are...
Host-microbiota, pro-inflammatory immunity and physiological senescence in wild birds
Těšický, Martin ; Vinkler, Michal (advisor) ; Tschirren, Barbara (referee) ; Štěpánek, Ondřej (referee)
Triggered by microbial ligands, inflammation serves as a "double-edged sword" to fight infections on the one hand, but on the other hand causing tissue damage due to oxidative stress if it is dysregulated. For example, chronic inflammation can contribute to inflammaging, which is now widely regarded as one of the causes of ageing. In my interdisciplinary dissertation, my colleagues and I investigated three interrelated aspects of inflammation, using an evolutionary framework and various free-living birds as models: (1) ecological and evolutionary determinants of gut microbiota (GM) composition and diversity, a driver of wild bird immunity, (2) diversity in immune genes affecting inflammatory responses in wild birds and (3) inflammation-related physiological senescence in a free-living passerine bird, the great tit (Parus major). Firstly, using 16S rRNA gene metabarcoding, we revealed high intra- and interspecific variation in passerine gut microbiota (GM) dominated by the major phyla Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Although in mammals GM depends strongly on host phylogeny and diet, in birds we found only moderate effects of phylogeny and very limited effects of host geography and ecology on GM composition. While microbiota diverged between the upper and lower...
Identification of new regulators of proinflammatory signaling pathways
Dráberová, Helena ; Štěpánek, Ondřej (advisor) ; Krulová, Magdaléna (referee) ; Funda, David (referee)
Identification of new regulators of proinflammatory signaling pathways Helena Dráberová Protein 4.1R has been described in immune system as regulator of migration and cell adhesion, but was also shown to play a role in activation of T lymphocytes. Polymorphism in gene ORMDL-3 is associated with asthma risk in children and correlates with increased ORMDL-3 expression. This disertation thesis describes the function of proteins 4.1R and ORMDL-3 in activation of mast cells after stimulation of FcεRI receptor. IL-17 is a proinflammatory cytokine that plays a role in immune response against fungal and yeast infections. IL-17 however also plays a role in the pathology of autoimmune diseases such as reumatoid arthritis, psoriasis and multiple sclerosis. IL-17 signaling is tightly regulated, however the exact mechanism has not been described. This disertation thesis describes the IL-17R complex by mass spectrometry and analyze the function of its known and newly discovered components in cells deficient in individual proteins by method CRISPR-Cas9. Last part focuses on the discovery of new subunit of IL-17RC protein CMTM4, which role in IL-17 signaling has not been described so far. CMTM4 stabilizes IL-17RC and is required for its surface expression. In vitro data are supported by data from autoimmune model of...
Searching for the common function of the BBSome across the evolution and development
Mašková, Kristýna ; Štěpánek, Ondřej (advisor) ; Čajánek, Lukáš (referee)
The BBSome is a protein complex whose function is associated with ciliary trafficking. It has been found that the BBSome is evolutionarily conserved among ciliated organisms. The disruption of the BBSome leads to cilia dysfunctions and affects many signalling pathways. In humans, genetic defects in the BBSome are the cause of Bardet-Biedl Syndrome, which is a pleiotropic disease. The BBSome is studied separately in various model organisms and cell lines to understand the molecular functions of the BBSome. These studies have not been compared to see if there is a common BBSome function, which could be why the BBSome is evolutionarily conserved among ciliated organisms. In this bachelor's thesis, the knowledge about the BBSome was summarized and compared to identify a putative common function of the BBSome among various model organisms or cell types. It seems that there has not been found any BBSome function that could be identified as the common function because the BBSome has many specialized functions in different organisms and tissues. The only distant similarity is BBSome-dependent ciliary retrograde transport, which has been described in most of the studied model organisms and cell types.
Mechanisms of the tolerance and homeostasis of immune cells
Tsyklauri, Oksana ; Štěpánek, Ondřej (advisor) ; Černý, Jan (referee) ; Froňková, Eva (referee)
The ability of the immune system to tolerate self-antigens while mounting appropriate responses to pathogens is indispensable for the survival of the organism. Despite years of research, many details of the mechanisms of self-tolerance are still not well understood. The objective of this thesis is to extend our knowledge of the mechanisms of immune tolerance. The core of the PhD thesis consists of five publications related to two main research directions. The first one addresses the mechanisms of peripheral immune tolerance established by regulatory T cells (Tregs). We showed that Tregs increase the quorum of self-reactive CD8+ T cells required for the induction of autoimmunity. In addition, we identified a novel subset of antigen-stimulated CD8+ T cells, which expand in the absence of Tregs. We called them super-effector T cells. We revealed that the administration of IL-2 phenocopies the absence of Tregs, i.e., it induces super- effector T cells, and enhances CD8+ T cell response in autoimmunity and cancer. Our results provide strong evidence that the major suppressive mechanism of Tregs is limiting IL-2 availability for CD8+ T cells. Furthermore, in a collaborative project, we have shown that MyD88 signaling in thymic epithelial cells contributes to the development of Tregs and thus to the...
The Industry Business of Prague Municipality in the first half of 20th Century. The Industrial Factories of Capital City Prague, ltd.
Štěpánek, Ondřej ; Jakubec, Ivan (advisor) ; Drnek, Kryštof (referee)
This work describes the industrial activities of the Prague municipality in building industry in the first half of the twentieth century, especially in the years 1921-1948, during which the company "Industrial factories of the Capital City of Prague" operated successfully in which the municipality owned half of the shares. The main objective is to monitor the activities of the company running the lime and brick factories and a sawmill. I focused on its development and significance. This thesis is based on information from the Prague City Archives, from the fund of Industrial Factories. The research illustrates the quantities of produced and sold building materials, then also important buildings in which the company was involved as a supplier. The main contribution of this work is the "re-discovery" of an interesting company which significantly supported the building industry in Prague, supplied the building material not only to municipal buildings and was a competitor for cartels.

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