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Immunological parameters in cerebrospinal fluid in children with autoimmune disorders of the central nervous system
Halmová, Hana ; Libá, Zuzana (advisor) ; Krejsek, Jan (referee) ; Uher, Tomáš (referee)
The central nervous system with its controlling and life-essential functions has a privileged position in our body. It has its own immune surveillance and is one of the immunoprivileged organs, in which immune reactions take place in specific ways. However, it is known that it is not entirely spared from immunopathological processes. Autoimmune diseases of the central nervous system are rare. Despite the growing diagnostic methods, the determination of an autoimmune aetiology of neurological disorders remains difficult. Thus, new diagnostic possibilities are constantly searched. The aim of this study was to investigate the levels of cytokines and chemokines in cerebrospinal fluid and serum in pediatric patients with various autoimmune diseases of the central nervous system as possible markers of inflammation. The contribution of our work is the potential in the use of cytokines and chemokines for the diagnosis of autoimmune diseases of the central nervous system when conventional diagnostic methods fail, as well as for the possible monitoring of the disease courses and the therapy effects. Our data may also contribute to the elucidation of the pathophysiology of individual diagnoses and to more effective and targeted therapy of these diseases in the future. Keywords: autoimmune diseases of the...
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Nanoparticles and Their Effect on the Immune System: Study of the Proinflammatory Potential of Selected Carbon Nanomaterials
Švadláková, Tereza ; Krejsek, Jan (advisor) ; Stulík, Jiří (referee) ; Roušar, Tomáš (referee)
Carbon-based nanomaterials (CNMs) have unique physical-chemical properties, which make them appropriate candidates for both industry and medicine. However along with production, there are growing concerns about their effects on human organism. For this reason, CNMs are frequent topic of toxicological studies. A key step in the clarification of their safety is to evaluate their interaction with the components of the immune system, particularly their ability to cause inflammation. For some allotropes e.g., pristine graphene derivatives, significant results are still missing or incomplete. For these reasons, this dissertation deals with the evaluation of the proinflammatory effect of two types of pristine graphene platelets (GPs), which represent common intermediate in the processing of other graphene derivatives, and which can penetrate to body via inhalation. For comparison, our work also includes an evaluation of the proinflammatory effect of multiwalled carbon nanotubes (MWCNTs). Professional phagocytes, particularly monocytes and macrophages represent key cells in processing and elimination of foreign and damaged or abnormal elements. Since phagocytes also represent main mediators of inflammation, we selected human primary monocytes and human monocytic cell line THP-1 differentiated in macrophages...
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Monitoring of Pleural Effusion Parameters During the Treatment of Chest Empyema
Matuchová, Inka ; Krejsek, Jan (advisor) ; Bobek, Vladimír (referee) ; Vodička, Josef (referee)
Monitoring of pleural effusion parameters during the treatment of chest empyema Chest empyema is a severe complication with collection of pus in the pleural cavity. The mortality rate of chest empyema is up to 40 %. Generally, treatment involves a drain insertion into the inflammatory focus and pleural space irrigation with local application of medication. These processes are usually lengthy with high risk of relapse. Our aim is to shorten the period of treatment using cytological-energy analysis of pleural effusions. This approach is based on simultaneous cytological and metabolic investigation of the pleural effusions. Results allow us to determine the type and intensity of local immune response in the pleural cavity. Repetitive investigations of pleural effusions in time give us information aiming the development of local immunity response in the pleural cavity and can follow the effect of therapy. Our goal is to define the theoretical framework for application of cytological-energy analysis of pleural effusions in patients with chest empyemas. The determination of the catalytic activities of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in pleural effusions as parameters of tissue damage is introduced by us. We established that cytological-energy analysis of pleural effusion...
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Molecular mechanisms of Francisella tularensis pathogenesis
Fabriková, Daniela ; Beránek, Martin (advisor) ; Krejsek, Jan (referee)
Title of Ph.D. thesis: Molecular mechanisms of Francisella tularensis pathogenesis Key words: Francisella tularensis, pattern recognition receptors, inhibition, TRAF6 and TRAF3 complexes Annotation Francisella tularensis is a highly infectious intracellular pathogen and the causative agent of the disease called tularemia. An important aspect of Francisella tularensis virulence represents the capacity to subvert the host immune response by inhibiting or disrupting of the innate immune cell functions. The initial stage of infection is characterized by the massive bacterial replication without apparent inflammatory response, which is crucial for the development of effective host defense against invading pathogen. The aim of this Ph.D. thesis was to describe the early pattern recognition receptors (PRR) signaling response to Francisella tularensis subsp. holarctica LVS (F. tularensis LVS) in primary bone marrow- derived macrophages. The obtained data show the capacity of F. tularensis LVS to simultaneously activate and suppress Toll-like receptors, RIG-I-like receptors, and cytosolic DNA sensors signaling pathways. F. tularensis LVS modulates these PRR pathways by the suppression of K63-linked polyubiquitination events and by the inhibition of the assembly of TRAF6 and TRAF3 signaling complexes. The use of the...
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Cholesterol depletion using reopheretic and apheretic processes and impact of these methods on immune system
Svrčková, Ellen ; Andrýs, Ctirad (advisor) ; Krejsek, Jan (referee)
LDL-apheresis and haemorheopheresis are the most frequent methods of extracorporeal ellimination methods used for lowering the LDL cholesterol in patients with familial hypercholesterolaemia (FH). In case of failure of conservative therapy (represented by pharmacotherapy and/or dietary regime) these methods reprensent the effective and accessible solution for the clinical status characterized by high morbidity and mortality as well. The lipid components are the most frequent observed markers for the effeciveness of intervention. However, immunity with its effector molecules plays also essential role and there is suppose, that could also reflect the state and progress of atherosclerosis in FH patients. The aim of this thesis was to evaluate the levels of selected immunological markers (plasmatic glykoprotein α-2-macroglobulin, IL-10, soluble endoglin, soluble apoptotic factor sAPO-Fas and soluble form of adhesive P-selectin) and their changes after LDL-apheresis and haemorheopheresis employing enzyme immunoanalysis and immuno nephelometry. Totally, 12 patients were involved in this study, 3 were treated by haemorheopheresis, the rest 9 received LDL-apheresis. As a results, significant decreases in serum levels of α-2- macroglobulin, soluble endoglin and sAPO-1/Fas were recorded. Observed changes of...
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Dendritic cells in health and disease
Horváth, Rudolf ; Špíšek, Radek (advisor) ; Krejsek, Jan (referee) ; Stříž, Ilja (referee)
During the past decades several spectacular finding s have been made in the field of immunology. Elucidating the functions of the antigen presenting cells (APCs) belong to the most important. Dendritic cells (DCs) represent a specific group of APCs with a unique ability to initiate primary immune responses. Despite the fact that, in vivo, they are very rare and difficult to isolate, DCs came very fast into the focus of scientific interests. Development of novel laboratory techniques facilitated a robust expansion of their research. With time it has been proven that DCs play a pivotal role in initiation, maintenance and control of the immune responses. The extraordinary features of DCs were soon investigated in human clinical trials, where DCs have been particularly used as vectors for vaccination protocols, especially in the treatment of tumors. However, DCs capability to polarize the outcome of immune response and the potential to induce or suppress immunity under specific circumstances led to the idea that they might be also used in the treatment of autoimmune and allergic diseases or in transplantation medicine as well. There is a need to stress that most of the knowledge has been obtained from the in vitro generated DCs, but advanced technological methods bring us the opportunity to study DCs directly...
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Rheopheresis for the cholesterol depletion and its immunological impact on patients with Age-related Macular Degeneration
Dreslerová, Ellen ; Jílek, Petr (advisor) ; Krejsek, Jan (referee)
of thesis: Rheopheresis for the cholesterol depletion and its immunological impact on patients with Age-related Macular Degeneration This thesis was focused on quantitative analysis of selected immunological-rheological parameters in the patients with age related macular degeneration employing ELISA based and immuno-nephelometric techniques. This disease is the most frequent reason of the blindness among the population alder than 60 years. The hemorheopheseris proved its statistically significant impact on the serum levels of α-2-macroglobuline (57%), P-selectine (17 %) and endogline (more than 15 %). The serum level of IL-10 was observed decreased about only 8,07 % and was characterized by the lower level of statistical significancy (p=0,0017). However, the decrease of the serum levels of hsCRP (22,11 %), IgM (62,14 %) and CMP-1 (14,15 %) was observed as highly statistical significant. All parameters correlate with the positive influence of the rheopheretic intervention and are in the concordance with the current literature. Finally, the results of the study showed the positive effect of the rheopheresis on the immunological parameters and support the application of this technique for the patients with age related macular degeneration.
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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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Tau protein, a biomarker of Alzheimer's disease: in vitro phosphorylation and tau-reactive antibodies characterization
Hromádková, Lenka ; Bílková, Zuzana (advisor) ; Fialová, Lenka (referee) ; Krejsek, Jan (referee)
Tau protein, a microtubule-associated protein localized in axonal projections of neurons, is a key molecule in the pathology of Alzheimer's disease (AD), the most common cause of dementia in the elderly population. Tau belongs to the group of natively unfolded proteins without globular structure and is prone to numerous posttranslational modifications (PTMs). Under pathological conditions, abnormal PTMs and misfolding of tau protein occurs and leads to oligomerization and aggregation into paired helical filaments forming neurofibrillary tangles, the histopathological hallmark of AD. Currently available drugs applied in AD treatment can only slow the disease progression and those, which halt the AD-specific neurodegenerative processes, are still missing. Very promising and evolving therapeutic approach is immunotherapy, and even immunomodulation by administration of intravenous immunoglobulin (IVIG) products, a reservoir of natural antibodies from the plasma of healthy donors, has been already tested. The discovery of naturally occurring antibodies directed to tau (nTau-Abs) in body fluids of both AD and healthy subjects and their presence in IVIG begin the investigation of their therapeutic potential. Considering a wide range of possible modifications of tau and of various tau species (oligomers,...
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Proteome analysis of secerned proteins of Francisella tularensis
Konečná, Klára ; Hernychová, Lenka (advisor) ; Krejsek, Jan (referee) ; Bílková, Zuzana (referee)
Title of dissertation thesis: Proteome analysis of secerned proteins of Francisella tularensis The facultative intracellular bacterium Francisella tularensis is the causal agent of the infectious disease called tularaemia. Despite the available wide range of new knowledge focused on bacterium Francisella, till now, mechanisms of tularaemia disease pathogenesis were not completely clarified. The contents of our work was based upon analysis and identification of culture filtrate proteins of bacterium F. tularensis of three strains (LVS, FSC00, SchuS4). Among identified proteins, there were seeked protein candidates for secretion and proteins, which could help with explanation of molecular mechanisms of disease pathogenesis caused by F. tularensis. The best protein candidate for secretion is enzyme acid phosphatase with proven important role in bacterium F. tularensis escape from phagosome. The attention was also focused on the new described mechanism of bacterial secretion, mediated by membrane vesicles. By the help of transmission electron microscopy was demonstrated, that F. tularensis of the strains LVS and FSC200 secretes membrane vesicles into extracellular milieu. Key words: Francisella tularensis, secretion systems, cultivation filtrate proteins, secreted proteins, outer membrane vesicles
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