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Mucosal immunity in upper respiratory tract diseases and autoimmunity diseases
Fundová, Petra ; Tlaskalová - Hogenová, Helena (advisor) ; Prokešová, Ludmila (referee) ; Bártová, Jiřina (referee)
Mucosal immune system comprises not only the major compartment of the immune system but also important interface with the outer environment. It is responsible in maintaining an intricate balance with the danger and non-danger stimuli of the outer world by employing specific anatomical features and unique functional mechanisms. Mucosal immune system has been long understudied, perhaps due to the limited accessibility, and its biological importance is thus still underevaluated. However, it has become evident that it is important to study mucosal immune system not only in local mucosal affections but also when uncovering pathogenic mechanisms and novel prevention strategies of organ specific autoimmune diseases such as type 1 diabetes. Thus, the first, more clinically oriented part of this thesis is focused on mucosal immune system of the upper respiratory tract in disease conditions - in nasal polyposis (NP). Because there is a substantial accumulation of eosinophils and neutrophils in the most frequent type of NP, we investigated and described increased expression of chemokine receptors CCR1 and CCR3 in NP versus nasal mucosa. Both innate immune mechanisms as well as homeostasis of epithelial cells may participate in NP. We have documented increased numbers of iNOS-positive and insulin-like growth...
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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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Characterization and utilization of feacal microflora components in experimental models of human civilisation diseases
Šrůtková, Dagmar ; Kozáková, Hana (advisor) ; Prokešová, Ludmila (referee) ; Mihál, Vladimír (referee)
Interaction between intestinal microbiota and host mucosal immune system plays crucial role in maintenance of mucosal homeostasis. Dysbiosis, altered composition of microbial communities, has been shown to be associated with life-style diseases such as inflammatory bowel disease (IBD) or allergies. In this regard, probiotics are valuable tool for the improvement of gut microbiota disbalance and proper stimulation of the immune system. In this thesis we focused on taxonomical classification of Bifidobacterium longum human origin strains by PCR-based methods, in vitro characterization of immunomodulatory properties of selected Bifidobacterium and Lactobacillus strains and evaluation of the beneficial effect of selected bacterial strains in IBD and allergy experimental mouse models. We investigated four different PCR-based methods and biochemical analysis for the taxonomical classification of twenty-eight B. longum isolates from the healthy human faeces. The Amplified Ribosomal DNA Restriction Analysis was the only method to be able to differentiate the analyzed strains into the B. longum/infantis subspecies. We showed that the analyzed immunostimulatory properties of bifidobacterial strains are strictly strain-specific. In a mouse model of acute ulcerative colitis, we have demonstrated that...
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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 study of food allergy in patients and experimental model
Goliáš, Jaroslav ; Tučková, Ludmila (advisor) ; Holáň, Vladimír (referee) ; Prokešová, Ludmila (referee)
Food allergy belongs among the most frequent disorders and its incidence is continuously rising over the last two decades in the developed world. Although the methods used in the diagnostics of food allergies are high sensitive, they have low specificity, which is affected by a purity of used extracts. Therefore, it is important to develop new proteomic procedures for isolation of food allergens in the pure and the biologically active forms, thereby improving the diagnostics of food allergies. Another approach for studying allergies is using an experimental model, which can help us to clarify the mechanisms of allergic response and the acquired findings employ in prophylaxis or allergy treatment. In the first part, we have developed a new proteomic procedure for isolation of wheat allergens in the purified form. By this procedure, using Rotofor, HPLC and electrophoretic methods, we identified 27 potential wheat allergens, from which 7 were newly identified: endogenous α-amylase/subtilisin inhibitor, trypsin/α-amylase inhibitor CMX1/CMX3, TLP, XIP-1, β-glucosidase, class II chitinase, and 26 kDa endochitinase. Further, we showed that isolated allergens (α-amylase 0.19, LTP, TLP, and wheatwin) retained their biological activity and were capable to activate basophils (BAT). In the second part, we...
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