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Immunologic Characteristics of Cord Blood in Children with Increased Risk of Allergy Development Preventive Use of Probiotics
Hrdý, Jiří ; Prokešová, Ludmila (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Ulčová-Gallová, Zdeňka (referee)
Allergy is one of the most common diseases. Identification of early prognostic markers pointing to an increased risk of allergy development is therefore of increasing importance. Cord blood represents an easily attainable clinical material for searching for prognostic markers signalizing future allergy development. Proportions of Th1 cytokines, Th2 cytokines and regulatory cytokines were tested in cord blood of children of allergic mothers (children in relatively high risk of allergy development) in comparison with cord blood of children of healthy mothers (low risk children). Also the activities of lymphocytes, dendritic cells (DC) and regulatory cells (Tregs) were compared in children of healthy and allergic mothers. The generally increased activity of both in vitro stimulated and non-stimulated mononuclear cord blood leukocytes was proved in children of allergic mothers in comparison with low risk children. The increased activity of DC of high risk children was detectable only after polyclonal stimulation. Significantly less pronounced functional properties of cord blood Tregs were found in children of allergic mothers when compared with children of healthy mothers. The increased reactivity of lymphocytes and DC together with the decreased activity of Tregs can support an easier...
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"DASH molecues" in local and systemic pathogenetic processes of rehumatoid arthritis
Šromová, Lucie ; Šedo, Aleksi (advisor) ; Borovanský, Jan (referee) ; Prokešová, Ludmila (referee)
The biological half-life of several pro-inflammatory mediators involved in the pathogenesis of rheumatoid arthritis (RA) is controlled by molecules exhibiting dipeptidyl peptidase-IV (DPP-IV)-like enzymatic activity (Dipeptidyl peptidase-IV activity and/or structure homologues- DASH). The aim of this thesis was to identify the molecular source of the DPP-IV-like enzymatic activity in the peripheral blood and synovial fluid in patients with rheumatoid arthritis as compared to control patients with osteoarthritis (OA), and to evaluate the association of DPP-IV with the disease activity. We found that the main source of the DPP-IV-like enzyme activity in the plasma and in the synovial fluid in patients with RA is the canonical DPP-IV. DPP-IV-like enzymatic activity and canonical DPP-IV were also detected on the cell surface of blood and synovial fluid mononuclear cells. Significantly lower DPP-IV-like enzymatic activity and DPP-IV expression in the synovial fluid mononuclear cells was found in RA as opposed to OA patients. In the synovial fluid of RA patients there was also a negative correlation between the concentration of the pro-inflammatory DPP-IV substrate SDF (stromal cell-derived factor-1 and the proportion of the DPP-IV+ T cells. The blood plasma DPP-IV-like enzymatic activity and...
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Identification of new virulence factors in intracellular pathogen Francisella tularensis
Daňková, Věra ; Szotáková, Barbora (advisor) ; Krejsek, Jan (referee) ; Prokešová, Ludmila (referee)
ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Věra Daňková Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of Doctoral Thesis: IDENTIFICATION OF NEW VIRULENCE FACTORS IN INTRACELULLAR PATHOGEN FRANCISELLA TULARENSIS This dissertation thesis is focused on the role of bacterial tetratricopeptide repeat-like (TPR-like) proteins in the pathogenesis of infection. As a model organism we have chosen highly virulent intracellular bacterium Francisella tularensis (F. tularensis), whose mechanism of pathogenesis is not completely described. In the first part of dissertation thesis we took advantage of bioinformatic methods and identified three genes (FTS_0201, FTS_1680, and FTS_0778) with predicted TPR-like domains. Mutants defective in protein expression were prepared by TargeTron insertion mutagenesis. Prepared mutant strains were used for studying the role of selected proteins in pathogenicity and immunogenicity of F. tularensis subsp. holarctica strain employing in vivo and in vitro models and further for studying the involvement of these proteins in stress tolerance. Our results showed that the FTS_1680 protein is required for intracellular replication and full virulence of bacterium. We also described impaired ability...
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The role of the immune system in the immunopathogenesis of autoimmune diseases and the therapeutic modulation of autoimmune reaction by tolerogenic dendritic cells
Dáňová, Klára ; Palová Jelínková, Lenka (advisor) ; Prokešová, Ludmila (referee) ; Heneberg, Petr (referee)
Immunotherapy based on dendritic cells (DCs) was first tested in clinical trials for the treatment of cancer in the 1990s. Currently, the ability of DCs to modulate immune responses is also being tested in several clinical studies focusing on autoimmune disease treatment with the aim of suppressing the overactivated immune system and restoring immune tolerance. For this purpose, so-called tolerogenic DCs with considerable suppressive potential are used. Tolerogenic DCs can be generated ex vivo from monocytes using pharmacological agents, which in DCs induce a regulatory phenotype with low expression of activation markers, high expression of inhibitory markers and secretion of suppressive cytokines. In the first part of this study, we show that cultivation of human blood monocytes in the presence of glucocorticoid dexamethasone and 19- nor-1,25-dihydroxyvitamin D2 (paricalcitol) enables ex vivo generation of tolerogenic DCs with a highly stable suppressive phenotype characterized by upregulated IL-10 production, inhibitory IL- T3 and PD-L1 molecule expression, the low stimulatory capacity and the ability to induce regulatory T cell development. Moreover, we show that metabolic changes and signaling through NF-κB, p38 MAPK, ERK1/2 molecules and the mTOR/STAT3 pathway play an important role in the...
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