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Heterogeneity of antigen-presenting cells in the thymus and its relevance for the establishment of central tolerance
Sýkora, Vojtěch ; Filipp, Dominik (advisor) ; Černý, Jan (referee)
The crucial function of the thymus is the establishment of central tolerance. In this process, developing T-cells are tested for their self-reactivity, since self-reactive T-cells might cause the autoimmunity if they would escape from the thymus to the periphery. Many thymic antigen-presenting cells are essential for establishment of central tolerance. Their role is to present self-antigens to the developing T-cells. Such presentation is capable to reveal the self-reactive potential of T-cells which can be then directly removed or deviated into suppressive T-regulatory cells. In the last several years, a high level of heterogeneity has been described among the thymic antigen-presenting cells and the molecular mechanisms that govern their functions towards enforcement of tolerance began to be uncovered. This thesis summarises recent knowledge in the field of heterogeneity of the thymic antigen-presenting cells and its relevance for establishment of the central tolerance, with the major focus on conventional dendritic cells and post-AIRE medullary thymic epithelial cells. This thesis also outlines recent advances in understanding of functional mechanisms and regulations of maturation of the antigen-presenting cells.
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De-escalation of the patient's aggressive behaviour in a psychiatric ward
Černý, Jan ; Jirkovský, Daniel (advisor) ; Dorková, Zlatica (referee)
The bachelor's thesis "De-escalation of aggressive patient behavior in the psychiatric ward" deals with the issue of aggression, its prevention and effective solution. The aim of the work was to determine the frequency of aggression, its type, cause and method of solution. Another aim of the work was to find out the frequency of trainings that the respondents completed and their interest in a possible offer of training focused on managing aggression. The theoretical part of the thesis provides a basic overview of the issue, a description of de- escalation techniques and other options for managing aggression and its prevention. The empirical part of the work presents the results of own research and their comparison with the results of other professional research. The method of the survey was a self-designed questionnaire, which was distributed to general and practical nurses of the Psychiatric Hospital Bohnice. 108 duly completed questionnaires were included in the study itself. Results: It was found that more than 58% of respondents experience verbal aggression at least once a week and almost 29% of respondents experience brachial aggression at least once a week. Due to such a frequent occurrence of aggression, only less than 59% of respondents have been trained in the issue at least once in the...
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Vliv antropogenních aktivit na společenstva vodních organismů v horní části povodí Litavky
ČERNÝ, Jan
The degradation of the natural environment is considered to be a global problem. Due to the importance of water sources, preservation and improvement of their quality are one of priority interest of all society. This study deals with the reactions of aquatic organism groups like fish and benthic invertebrates to an anthropological effect in the Litavka basin. Researched part of Litavka is polluted by toxic heavy metals from past ceveral centuries of extensive mining and industrial smelting in its close proximity. It is also polluted by releasing wastewaters, which contain xenobiotics, trash, and decomposing organic matter. The Obecnický stream was chosen as a reference locality because it is the most similar to a clear natural habitat. It flows into the Litavka river in a spot, where the riverbed is channelised and its floodplain is occupied by toxic waste dumps. The Obecnický stream can be considered the most important water source in the upper Litavka basin regarding the current hydrological conditions. Autochthonous fish population in the upper Litavka basin suffer from several water abstractions, which change temperature and flow regimes. It was our effort, to evaluate the influences of these anthropological factors on aquatic biota, aiming to above-mentioned pollution types, and presence of the water reservoir situated on the Obecnický stream. Monitoring of organism and environmental data collecting (physically chemical parameters, NH4+ , NO2-, PO43-, bottom substrate, flow, and others) were always implemented parallelly. In the case of fish species groups, the resulting correlations show us the greatest impact of the temperature gradient and zinc concentration. We found out a negative correlation between zinc concentrations and abundances of brown trout (Salmo trutta morpha fario) and brook lamprey (Lampetra planeri). On the other hand, common minnow (Phoxinus phoxinus) was highly tolerant for this kind of pollution. The abundance of brown trouts decreased with increasing temperature and it seemed as beneficial for common minnow populations. There was also a shift in the community of invertebrates, namely total absence of three mayflies families (Ephemerellidae, Heptageniidae and Leptophlebidae), Gammaridae, the sphaerid clam Pisidium sp. and the river limpet (Ancylus fluviatilis). The inflow of the wastewaters was accompanied with considerable increase of biomass of common several cyprind species. Besides that, there was a high density of eruciform caddisflies of genus Micropterna and Halesus. Within particular benthic invertebrates, domination of dipteran insects, leeches (Hirudinea) and the freshwater waterlouse (Asellus aquaticus) was observed under the outcome of wastewaters.
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Antivirotické účinky biologicky aktivních látek z přírodních zdrojů v kombinaci s imunomodulačními látkami proti viru klíšťové encefalitidy
ČERNÝ, Jan
The aim of this study is focused on substances from the nature as a potentional treatment against tick-born encephalitis virus. The research of this master thesis can be divided into two sections. The first one is about choosen derivatives of adamantane, their cytotoxic effect on neuron cell lines and the determination of their antivirotic properties in vitro. For these purposes was used the combination of MTT assay, plaque titration assay and one-step qRT-PCR. The second part of this work verified the capability of choosen stilbenes to prolong the life of BALB/c mice which were infected by tick-born encephalitis virus.
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Mechanisms underlying subversion of host immunity by Bordetella pertussis
Klímová, Nela ; Bumba, Ladislav (advisor) ; Černý, Jan (referee) ; Filipp, Dominik (referee)
Bordetella pertussis is a Gram-negative human-adapted pathogen of the respiratory tract and the causative agent of the whooping cough (pertussis) illness. The bacterium produces a number of virulence factors, of which adenylate cyclase toxin (ACT) and pertussis toxin (PT) play important roles in manipulation of host immune response and establishment of the early catarrhal stage of infection. Although the toxins exert their cytotoxic activity by elevation of intracellular cAMP levels, both are distinct from each other in terms of their structures, mechanisms of secretion and cell intoxication, as well as in their ability to modulate the adaptive immune response of the host. The aim of this thesis was to determine the structure- function relationship underlying the mechanism of the Type I secretion system (T1SS)- mediated secretion of ACT and to decipher the immunomodulatory properties of ACT and PT in the course of B. pertussis infection. Integrative structural biology approaches revealed that the RTX domain of ACT consists of a contiguous assembly of five Ca2+ -loaded β-roll blocks, whose co-secretional folding constitute an intramolecular Brownian ratchet that prevents backsliding of the translocating polypeptide in the T1SS conduit, thus accelerating the secretion of ACT from bacterial cells by a...
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Effect of endosymbionts on composition and properties of Trichomonas vaginalis exosomes
Zdrha, Alois ; Tachezy, Jan (advisor) ; Černý, Jan (referee)
Trichomonas vaginalis is a parasite of the human reproductive tract and the causative agent of trichomoniasis, the most spread non-viral sexually transmitted disease. Although trichomoniasis usually has mild symptoms, it can lead to serious adverse effects. The course of the disease is influenced by the host immune system, microbiome and virulence of the parasite. Importantly, the virulence of T. vaginalis is extremely variable, and it depends on secreted and surface molecules. Among these are proteases and adhesins, which can be secreted as part of the secretome or through extracellular vesicles (EVs). Further potential virulence factors are the endosymbionts of T. vaginalis: Trichomonas vaginalis virus (TVV) and Mycoplasma hominis. Although extensively studied, no consensus on whether TVV exacerbates trichomoniasis has been reached. The aim of this thesis is to analyse the effect of TVV on the protein and RNA exosomal cargo and to assess the cytokines induced by exosomes of TVV-positive T. vaginalis. Key words endosymbionts, dsRNA virus, TVV, exosome, parasite, Trichomonas vaginalis, bioinfor- matics
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Role of type 3 innate lymphoid cells mediated antigen presentation in prepipheral tolerance establishment
Machač, David ; Filipp, Dominik (advisor) ; Černý, Jan (referee)
Mutual tolerance between organisms is a key evolutionary mechanism for the emergence of commensal and mutualistic relationships. In case of the immune system, the creation of tolerogenic mechanisms towards our own tissues, but also commensal-mutualistic organisms and food antigens, together with defensive components of immunity and their balanced action, is a necessary condition for our survival. To better defend against pathogens, adaptive immunity with randomly assembled TCR and BCR receptors of lymphocytes has evolved. T lymphocytes capable of recognizing the body's own antigens are either deleted (recessive tolerance) or converted to regulatory T cells (Tregs) (dominant tolerance) in the thymic medulla by mechanisms which is collectivelly referred to as central tolerance. Compared to the establishment of central tolerance, the establishment of peripheral tolerance is a more demanding process in terms of the enormous variability of microorganisms living on our mucosal surfaces and skin along with the exposure to a wide variety of food antigens during ontogenesis. It has been shown that innate lymphoid cells expressing the RORγt transcription factor have the ability to present antigens derived from intestinal microorganisms and thus perform the deletion of T lymphocytes recognizing these antigens. These...
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CX3CR1+ migratory dendritic cells in the mechanisms of central tolerance
Březina, Jiří ; Filipp, Dominik (advisor) ; Černý, Jan (referee)
Display of thousands of self-antigens in the thymus is fundamental for the establishment of central tolerance as its failure can lead to the development of autoimmunity. Medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs) constitute essential populations of antigen presenting cells (APCs) which present these self-antigens to developing T cells. While mTECs produce and present antigens in self-autonomous manner, DCs can hijack mTEC-derived antigens by the process of cooperative antigen transfer (CAT). It is well found that CAT is essential for working central tolerance, however, the overall heterogeneity of thymic APCs participating in CAT remains unclear. Using transgenic mouse models and multicolor flow cytometry analysis, we determined that APCs involved in CAT are exclusively of CD11c+ phenotype. Within these cells, we identified previously unrecognized CX3CR1+ subset of migratory DCs (mDCs) exhibiting monocyte/macrophage markers. These CX3CR1+ mDCs are more efficient in CAT than their CX3CR1- counterparts and reveal robust antigen presenting properties with the capability to present CAT-acquired antigen. Genetic ablation of CX3CR1+ mDCs resulted in increased cellularity of CD8+ and CD4+ thymocytes, indicating importance of this mDC subset for negative selection of...
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Exploring novel strategies targeting HBV
Šmilauerová, Kristýna ; Grantz Šašková, Klára (advisor) ; Černý, Jan (referee)
An effective and safe vaccine against Hepatitis B virus already exists, yet morbidity and mortality of this illness are still high. The key to developing a reliable treatment is a deep knowledge of the virus' life cycle and functions of all its components. In the presented work we explored an interactome of the Core protein of the Hepatitis B virus. Using proximity-dependent biotin identification technique (BioID) coupled to mass spectrometry we have identified a list of potential candidates that are either significantly enriched (in total 105 proteins) or less abundant in the presence of the HBV Core protein in the cell (40 proteins). The list also includes known HBV Core interacting proteins SRPK1 and SRPK2, and p53 protein whose expression is known to be repressed due to the HBV Core interaction with the E2F1 transcription factor. Many of the newly identified possible HBV Core interacting proteins are involved in biological processes already known or are suspected to be influenced by the HBV such as translational and transporting processes or gene expression and macromolecule production. Overall, this work comprehensively characterizes the interaction landscape of the HBV Core protein in the live cells and might thus serve as a reliable start for in depth HBV-host interaction analysis. Key...
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