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Dissertations / Theses on the topic 'Autoimunitní'
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Klinková, Michaela. "Management pacientů s roztroušenou sklerózou." Master's thesis, Vysoká škola ekonomická v Praze, 2012. http://www.nusl.cz/ntk/nusl-165378.
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This diploma thesis is about the illness called multiple sclerosis. The theoretic part describes this illness, its history, types of multiple sclerosis and refers to economic costs. The practical part detected the position of patients and evaluates their quality of life. The most important in this part are economic costs of patient and economic costs of insurance companies.
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Florea, Florina [Verfasser], and Cassian [Akademischer Betreuer] Sitaru. "Pathogenic autoimmunity against skin laminins = Pathogene Autoimunität gegen Laminine der Haut." Freiburg : Universität, 2012. http://d-nb.info/1123474478/34.
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Kučinskienė, Gintarė. "Autoantikūniai ant šunų eritrocitų ir trombocitų: nustatymas ir funkcinė svarba." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2004~D_20051230_133207-37836.
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In this study, we demonstrated that membrane immunofluorescence (MIF) with canine erythrocytes is a much more sensitive diagnostic technique compared with the Coombs test to detect auto-antibodies on RBC. We also demonstrate how the evaluation of the MIF test can be made more precisely which results in a more clear interpretation. Till nowadays the Evans syndrome (combined thrombocytopenia and anemia) is not very well diagnosed in dogs. Only a few studies with low animal numbers tested auto-antibodies on RBC and thrombocytes. Here we describe the frequency of Evans syndrome based on the evaluation of a large data set with 557 dogs. The novelty of the thesis also lies in making a research of the amount of CICs in sera of AIHA/AITP patients is described as well as the cytotoxic potential of patient’s sera for canine leucocytes. These new aspects of diagnosis (AIHA) and pathogenesis (AIHA/AITP) are not only relevant for dogs but also for humans and can be used for better differential diagnosis in medicine. The new findings with respect to circulating immune complexes and cytotoxicity are also offer new therapeutic concepts. Besides, the study has resulted in the characterization of monoclonal antibodies which allow for the detection of so far undetectable canine differentiation antigens (CD molecules) on canine erythrocytes (CD235) and thrombocytes (CD42a). The identified mAbs are useful in the identification of relevant target structures for autoantibodies on these cells.
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Apert, Cécile. "L'IL-2 et l'IL-15 façonnent le développement thymique des lymphocytes T régulateurs." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30313.
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Les lymphocytes T régulateurs exprimant le facteur de transcription Foxp3 (Treg) jouent un rôle majeur dans le contrôle des différents types des réponses immunitaires. Leur rôle est crucial puisqu'une absence totale de Treg chez la souris ou chez l'humain entraîne des pathologies auto-immunes létales, respectivement Scurfy and IPEX. Les Tregs sont également impliqués dans d'autres processus tels que la réparation tissulaire, le contrôle des inflammations chroniques et la tolérance fœto-maternelle et présentent de ce fait une hétérogénéité fonctionnelle. Certaines de ces spécifications fonctionnelles sont acquises en périphérie mais des données de la littérature suggèrent qu'une hétérogénéité des Tregs apparaît dès leur développement dans le thymus. Durant celui-ci, les précurseurs des Tregs interagissent avec des cellules stromales thymiques. Celles-ci expriment des complexes CMH:peptide reconnus par les précurseurs des Tregs grâce à leur récepteur à l'antigène, le TCR, et délivrent d'autres signaux, par exemple cytokiniques, nécessaires au développement des Tregs. Mon projet de thèse a visé à étudier les effets respectifs de deux interleukines, l'IL-2 et de l'IL-15, sur le développement des différentes sous-populations de Tregs. Après avoir confirmé l'importance quantitative de ces cytokines pour le développement des Tregs, nous nous sommes intéressés à l'aspect qualitatif de celui-ci. J'ai effectué des analyses de cytométrie et transcriptomiques (CITEseq) sur les Tregs en développement les plus matures afin de dresser l'inventaire détaillé des différentes sous-populations des Tregs thymiques. Mes résultats montrent une diversité fonctionnelle des Tregs en développement bien plus importante que celle rapportée dans la littérature. De plus, mes données suggèrent un besoin différent en IL-2 et IL-15 pour le développement des sous-populations de Tregs identifiées. Nos analyses par séquençage à haut débit du répertoire des TCR exprimé par les Tregs qui se développent en absence d'IL-2 ou d'IL-15, ont montré des répertoires partiellement différents des Tregs. Différentes sous-populations de Treg, avec des répertoires TCR et des besoins en cytokines distincts, se développent donc dans le thymus. A terme, la compréhension des implications exactes de ces sous-populations dans les différentes fonctions exercées par les Tregs permettra de les cibler dans le cadre du traitement de pathologies dans lesquelles le système immunitaire joue un rôle central, telles que les pathologies auto-immunes, l'inflammation chronique, le rejet des allogreffes et le cancerRegulatory T cells that express the transcription factor Foxp3 (Treg) play a major role in controlling different types of immune responses. Their role is crucial since a total absence of Treg in mice or humans leads to lethal autoimmune pathologies, respectively Scurfy and IPEX. Tregs are also involved in other processes such as tissue repair, chronic inflammation control and maternal fetal tolerance and thus present a functional heterogeneity. Some of these functional specifications are acquired in the periphery but some data from the literature suggest that this Treg heterogeneity appears as soon as they develop in the thymus. During their development, the Treg precursors interact with thymic stromal cells which express MHC:peptide complexes recognized by Treg precursors trough their antigen receptor, TCR, and deliver other signals, for example cytokines, necessary for the development of Tregs. My thesis project aimed to study the effects of two interleukins, IL-2 and IL-15, on the development of different Treg subpopulations. After having confirmed the quantitative importance of these cytokines for the development of Tregs, we were interested in the qualitative aspect of this one. I performed cytometry and transcriptomic analyzes (CITEseq) on the most mature developing Tregs in order to draw up a detailed inventory of the different subpopulations of thymic Tregs. My results show a functional diversity of developing Tregs, much larger than the one reported in the literature. In addition, my data suggest a different need for IL-2 and IL-15 for the development of the identified Treg subpopulations. Our high throughput sequencing analyzes of the TCR repertoire expressed by Tregs that develop in the absence of IL-2 or IL-15, showed partially different Treg repertoires. Therefore, we showed that different Treg subpopulations, with different TCR repertoires and cytokine requirements, develop in the thymus. In the long term, understanding the exact implications of these subpopulations in the various functions exercised by the Tregs will help to target them in order to treat diseases in which the immune system plays a central role, such as autoimmune diseases, chronic inflammation, allograft rejection, and cancer
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Martins, Carlo de Oliveira. "Análise proteômica diferencial em válvula mitral na doença reumática cardíaca." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-02082013-142739/.
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A Doença Reumática Cardíaca (DRC) é uma séria complicação de orofaringite causada por determinados sorotipos de Streptococcus pyogenes não tratada adequadamente em indivíduos suscetíveis. É um grande problema de saúde pública, principalmente nos países não desenvolvidos e em desenvolvimento, como Brasil, Índia, países da África, regiões de população aborígine da Austrália, e Egito. É altamente debilitante e com alta taxa de mortalidade devido ao comprometimento cardíaco. As lesões miocárdicas iniciais regridem, mas as lesões valvares, principalmente a mitral e a aórtica, são irreversíveis e progressivas. Muitos estudos já caracterizaram a resposta imune celular (linfócitos T) e humoral nos indivíduos acometidos pela doença. Mimetismo molecular e espalhamento de epítopo são os principais mecanismos que se pensa estar envolvidos na patogênese da DRC. Avaliamos, nesta pesquisa, o perfil de expressão proteica em valvas mitrais de indivíduos acometidos por DRC. Para detectar alterações específicas desta doença, comparamos as expressões de proteínas nos grupos portadores de DRC com insuficiência (DRC-INS) e com estenose (DRC-EST) a um grupo de indivíduos com degeneração mixomatosa de valva mitral (DMX) e outro sem valvulopatias (CTL). Alterações especificamente observadas em tecido mitral na DRC-INS ou DRC-EST em fases avançadas da doença podem explicar o mecanismo de desenvolvimento desses dois tipos de lesão. Foram encontradas 25 \"spots\", correpondendo a 29 proteínas diferencialmente expressas nos grupos com valvulopatias, refletindo principalmente alterações na matriz extracelular. Encontramos importante clivagem diferencial da vimentina, cuja proteína íntegra possui 54 kDa, formando fragmentos com ~40 e ~45 kDa, aumentados na DRC, principalmente na DRC-INS. O colágeno do tipo VI, com aproximadamente 95 kDa, encontrou-se com expressão diminuída exclusivamente no grupo DRC-INS. A Vitronectina foi encontrou-se aumentada em na DMX e na DRC-EST, em relação ao grupo controle, principalmente na DRC-EST. Lumican, por sua vez, teve expressão diminuída na DMX e na DRC-EST, apesar de possuir um único \"spot\" com expressão aumentada na DRC. Utilizando métodos de análise de padrões de expressão protéica in silico foram identificados conjuntos de proteínas capazes de discriminar as amostras de valva mitral por etiologia da doença. O presente trabalho pode auxiliar na elucidação dos mecanismos de desenvolvimento da doença e de alterações estruturais do tecido mitral em resposta às lesões autoimunes, bem como no diagnósticoda DRC.Rheumatic Heart Disease (RHD) is a serious complication of oropharingitis caused by some serotypes of Streptococcus pyogenes not properly treated in susceptible individuals. It is a public health concern, mainly for undeveloped and developing countries, such as Brazil, India, some countries in Africa, aboriginal regions in Australia, and Egypt. It is highly debilitating with a high mortality rate due to cardiac commitment. Initial myocardial lesions disappear, but valvar lesions, mainly mitral and aortic, are irreversible and progressive. Many studies have characterized cellular (T lymphocytes) and humoral responses in individuals affected by the disease. Molecular mimicry and epitope spreading are the main mechanisms thought to be involved in the pathogenesis of RHD. We evaluated, in this research, the profile of protein expression in mitral valves from individuals affected by RHD. To detect alterations specific of this disease, we compared protein expression in the group of RHD with regurgitation (RHD-RGT) and stenosis (RHD-STN) to a group of individuals with mitral valve myxomatous degeneration (MXD) and another group without valvulopathies (CTL). Alterations specifically observed in the mitral tissue of RHD-RGT and RHD-STN in advanced stages of the disease can explain the mechanism of development for these two kinds of lesions. Twenty-five spots, corresponding to 29 proteins were found to be differentially expressed in the valvulopathy groups, reflecting mainly alterations in extracellular matrix. We found important differential cleavage of vimentin, the whole protein having 54 kDa, in fragments with ~40 and ~45 kDa, increased in RHD, mainly in RHD-RGT. Collagen type-VI, with approximatelly 95 kDa, was found to have decreased expression exclusivelly in the RHD-RGT group. Increased expression of Vitronectin was detected in DMX and RHD-EST groups, compared to the CTL group, mainly in the RHD-STN. Lumican, in turn, had decreased expression in the MXD and RHD-STN groups. By using in silico methods for analysis of patterns of protein expression, we identified sets of proteins capable of discriminating mitral valve samples by disease etiology. The present study might help elucidating the mechanisms of disease development and structural alterations in the mitral tissue in response to the autoimmune lesions, as well as in the diagnosis of RHD.
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Novosádová, Iva. "Imunologický profil experimentální autoimunitní encefalomyelitidy." Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-306680.
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5 Anglický abstrakt Experimental autoimmune encephalomyelitis (EAE) is widely accepted as a murine model of human multiple sclerosis autoimmune disease. Murine EAE is usually actively induced by immunization with a suitable myelin antigen. Following immunization, CD4+ T helper lymphocytes Th1 and Th17 accumulate in the nervous tissue and via the production of cytokines, they mediate an inflammatory reaction and the subsequent destruction of myelin. The main goal of this study was the induction of EAE with clinically observable symptoms and the observation of changes in the counts and phenotypes of cells, mainly NK and T cells. NK cells express a wide range of inhibitory and activation receptors from the C-lectin-like receptor superfamily. The specific ligand of the activating NKR-P1C isoform is still unknown and thus this receptor's involvement in EAE was also observed. Another goal was the use of medication with regard to the disease progress improvement. For the purposes of this study, two inbred murine strains with distinct NKR-P1 surface expression were used - the SJL/J strain (expressing inhibitory NKR-P1B) and C57BL/6 (expression activating NKR-P1C). SJL mice elicited a relapse-remitting of EAE, while C57BL/6 had chronic EAE. Both mouse strains exerted changes in the counts of NK...
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Dáňová, Klára. "Role imunitního systému v imunopatogenezi autoimunitních chorob a možnosti terapeutického ovlivnění autoimunitní reakce tolerogenními dendritickými buňkami." Doctoral thesis, 2019. http://www.nusl.cz/ntk/nusl-403395.
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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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Richter, Jan. "Úloha NK buněk v patogenezi autoimunitní artritidy." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-333577.
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Rheumatoid arthritis (RA) is a worldwide problem representing one of the most prevalent autoimmune diseases in the world. Despite the commonness of the disea- se, its pathogenesis has not been fully described. Immune cells ranging from antigen- presenting cells to T, B and NK cells playing various roles participate in the rheumatic process. In this work we concentrated on NK cells expressing a repertoire of activating and inhibitory receptors which influence their function in health and disease. We focused on the analysis of NK cell function and described its possible modulation by rheumatic autoantigens and multivalent glycodendrimers bearing 4 (GN4C) or 8 (GN8P) N-acetyl glucosamine moieties. The effect on NK cells and the glycosylation pathways was further studied in vitro. Finally, an in vivo study was performed on an animal model of RA - col- lagen-induced arthritis (CIA) to assess the effect of the compounds on clinical develop- ment of the disease and selected immune parameters. Comparison of NK cell cytotoxicity in patients suffering from RA, other inflam- matory diseases and healthy donors showed its impairment particularly in RA patients. Peripheral blood NK cells reacted to GN8P glycoconjugate by inhibition of their effector function in CD161 high-expressing samples. The MGAT5...
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Kayserová, Jana. "Poruchy regulace imunity - alergie a autoimunitní onemocnění." Doctoral thesis, 2013. http://www.nusl.cz/ntk/nusl-328207.
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The pathology of immune system can lead to immune disorders. Immunodeficencies are caused by insufficient or missing immune response. On the other hand, allergies and autoimmune disorders represent a consequence of wrong control of the immune reaction and breakdown of an immune tolerance. Immunopathogenesis of allergic and autoimmune diseases are to some extent common to both immunopathologies; both represent harmful hypersensitive reaction to autoantigen or allergen and lead to the destruction of tissues and organs or to their dysfunction. Allergy and autoimmunity result from the combination of internal, mainly genetic, and external factors, such as infection. In this thesis, we focused on the mechanisms that lead to the disorders of regulation of immune reaction. We studied cohorts of patients with allergy or autoimmunity and we concentrated first on the genetic omponents that underlie both immun opathologies, furtheron mechanisms of innate immunity, particularly dendritic cells and finally on the adaptive immunity, mainly B cells and antibodies. One of our projects presented our experience with the therapy influencing B lymphocytes using monoclonal antibody against CD20 (rituximab). In summary, our studies present a complex view on immune reactions that contribute to allergic and autoimmune diseases. Our...
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Klímová, Aneta. "Mechanismy patogeneze experimentální autoimunitní uveitidy a možnosti jejich ovlivnění." Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-265174.
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Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...
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Seidler, Štangová Petra. "Studium imunopatologických mechanismů autoimunitní uveitidy a definování nových terapeutických možností." Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-415776.
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The aim of this work was to gain new knowledge about mechanisms of autoimmune uveitis and to test new therapeutic possibilities that have not yet been studied in uveitis or whose effect is questionable. The main emphasis was placed on the role of microorganisms in the process of uveitis. A mouse model of experimental autoimmune uveitis including a germ-free model was used to achieve the aims and samples of patients' intraocular fluids were analyzed. In the experimental model, the intensity of inflammation was evaluated in vivo clinically and post mortem histologically. The effect of immunomodulatory treatment was evaluated. The intensity of inflammation was compared between groups of germ-free and conventional mice. The therapeutic effect of antibiotics administered to affect microbiome was investigated in conventional mice. In intraocular fluid samples of patients with autoimmune uveitis signs of infection were monitored and levels of cytokines and other factors were evaluated. Evaluation of the effect of immunomodulatory therapy has demonstrated the efficacy of mycophenolate mofetil, which supports its wider use in the treatment of autoimmune posterior uveitis in human medicine. The decrease in bacterial load has led to a decrease in the intensity of inflammation, thereby confirming the importance of...
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Šlemín, Johan. "Vliv střevní mikrobioty na slizniční a systémovou imunitu při experimentální autoimunitní uveitidě." Master's thesis, 2021. http://www.nusl.cz/ntk/nusl-447086.
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The use of probiotics has emerged in the last decades as a promising strategy when it comes to the treatment of inflammatory diseases. Through modulation of composition of the intestinal microbiota and the signalling it provides, probiotics can favourably tune the immune system. Beneficial effects of probiotic treatment have been documented in multiple animal inflammatory disease models. The effect of probiotic treatment on uveitis-a sight- threatening disease-has however not yet been described. In our study, we have tested two commercially available probiotics-Escherichia coli Nissle 1917 (EcN) and Escherichia coli O83:K24:H31 (EcO)-in the treatment of experimental autoimmune uveitis (EAU). The disease severity was assessed by ophthalmoscopy and histology, proportions of leukocyte populations and intracellular expression of cytokines were evaluated by flow cytometry and the gut immune environment was analysed by tissue culture and ELISA. We found that prophylactic and early oral treatment with EcN reduces the severity of EAU. However, EcO treatment does not. The effects were accompanied by immune changes including a lowered production of inflammatory cytokines in Peyer's patches, a shift in macrophage populations in ileum and mesenteric lymph nodes or a reduced IRBP-specific response of CD4+ T...
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Špitálníková, Sylvie. "Autoimunitní onemocnění štítné žlázy v těhotenství a v puerperiu (Screening tyreopatií v těhotenství)." Doctoral thesis, 2011. http://www.nusl.cz/ntk/nusl-299598.
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Our universal screening revealed a relatively high prevalence of autoimmune thyroid disorders (AITD), namely Hashimoto's thyroiditis (HT) and postpartum thyroiditis (PPT), and incipient hypothyroidism in an unselected population of pregnant women from a chosen district, roughly similar to that in foreign studies. Most of the disorders recognized in this way were asymptomatic, and if only high-risk women, defined according to the recommended guidelines, were examined, a large proportion of pregnant women with thyroid disorders would be neither followed by an endocrinologist, nor treated. The universal screening for thyroid autoimmunity and dysfunction appears to be more beneficial for improving the care of pregnant and postpartum women and their children than limiting the testing on women with risk factors only. For the evaluation of TSH levels in pregnant women in the first trimester of pregnancy, the range 0.15-3.5 mIU/l appeared to be the most appropriate one with respect to the method used. On the basis of the results obtained, we believe that the use of the screening target of 3.5 mIU/l and the treatment target of 2.5 mIU/l in women identified as having HT brings satisfactory outcomes. Pregnant women who were treated properly and in time showed a lower occurrence of complications in pregnancy....
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Kosová, Hana. "Autoimunitní poškození ovária u dospívajících dívek, vliv antiovariálních protilátek na poruchy menstruačního cyklu a fertilitu." Doctoral thesis, 2006. http://www.nusl.cz/ntk/nusl-266785.
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Srbová, Libuše. "Aspirační cytologie štítné žlázy - význam hodnocení podle Bethesda klasifikace, výskyt diferencovaného karcinomu při autoimunitní tyreoiditidě." Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-352052.
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Aspiration biopsy of the thyroid - the significance of evaluation according to Bethesda classification, differentiated carcinoma incidence in autoimmune thyroiditis. Introduction: Improved diagnostics led to an increased number of detected thyroid nodules. Sonography and fine needle thyroid biopsy has become the basic method for thyroid nodules evaluation. Since 2010 the Bethesda System for Reporting Thyroid Cytopathology is used in some centres. Another common thyroid disease is autoimmune thyroiditis. According to some older studies a nodule in a patient with thyroiditis has a higher risk of malignancy. Current opinions dispute these findings. The difference in data appears to depend primarily on whether cytological or surgical findings are analysed. Objective: The aim of our study was to reclassify thyroid biopsy results according to the Bethesda categories in patients who underwent thyroidectomy and to determine the malignant potential of the individual categories. We then determined in equivocal cytological findings whether the recommendations for surgery, the type of cytologic atypia and the results of repeated biopsies had an impact on the incidence of malignant findings. Another objective was to identify how autoimmune thyroiditis affects the risk of thyroid cancer, particularly by comparing...
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Uher, Martin. "Pulsní léčba glukokortikoidy a změny exprese mikroRNA u pacientů se systémovými autoimunitními onemocněními." Master's thesis, 2018. http://www.nusl.cz/ntk/nusl-380761.
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Rheumatoid arthritis is the most common joint disease of autoimmune origin. It is accompanied by inflammatory conditions that lead to irreversible changes in the joints, their deformities ending with permanent disability. Treatment of the disease involves routine regimens, surgical, as well as pharmacological treatment, which is necessary for advanced forms. Glucocorticoids play an important role in the therapeutic intervention in the course and progression of the disease. In spite of their anti-inflammatory effect, which is a key to improving the condition of the patient, they have a number of side effects in the long term- use. In this study, we have focused on the impact of these drugs on microRNA expression changes in arthritic patients treated with pulsed doses of glucocorticoids. MicroRNAs are nowadays widely studied due to their possible use as biomarkers in monitoring disease progression and the effect of treatment. MiRNA expression analysis was performed by quantitative real-time PCR array of 754 miRNAs with reverse transcription using stem-loop primers that allow amplification of short sequences that microRNAs are. Data analysis revealed 29 miRNAs differentially expressed at the significance level p ≤ 0.05, 14 miRNAs were at significance level p ≤ 0.025 (respectively 7 miRNAs at p ≤ 0.005...
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Neuwirth, Aleš. "Defensiny a autoimunita: Nový model využívající alfa-defensiny pro studium mechanismů autoimunitních dějů." Doctoral thesis, 2012. http://www.nusl.cz/ntk/nusl-305926.
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The process of immune "self-nonself discrimination" is of utmost importance for the survival of all species as the biodestructive force of immune system can be directed towards the host as much as to pathogens. Thus, to shift this balance towards the latter, T cells bearing self- recognizing receptors are removed in the thymus (central tolerance) or their reactivity is harnessed through various additional mechanisms in periphery (peripheral tolerance). If the selfreactive T cells are not deleted and persist in the body, the regulation of self-tolerance can be breached, leading to the onset of autoimmunity. Presented thesis revolved around α-defensins, very effective bactericidal peptides that represent an important part of humoral innate immunity. There are two types of α-defensins: myeloid, expressed predominantly in neutrophils, and enteric, synthesized by intestinal Paneth cells. Data presented inhere are first to characterized the involvement of α-defensin- expressing cells in two types of autoimmune diseases, insulin-dependent diabetes mellitus (T1D) and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). The former relates to the identification of transcriptionally activated myeloid α-defensin- expressing eosinophils present in the thymus of diabetes prone rat. In...
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Buchtelová, Aneta. "Glaukom - genetická analýza rodiny ve vztahu k autoimunitnímu pozadí." Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-405689.
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Introduction: Recent findings about the pathogenesis of glaucoma have already demonstrated the presence of some specific autoimmune mechanisms. It has also been shown that autoimmune diseases often manifest in co-occurrence, such as celiac disease and type 1 diabetes mellitus or psoriasis. This association can be explained by sharing some of the risk variants of HLA molecules class II. Considering glaucoma an autoimmune disease, the question raises how the glaucoma genetic risk factors affect the phenotype of another autoimmune disease or vice versa, whether genetic risk variants associated for example with celiac disease can affect the glaucoma phenotype. Aims: The aims of this study were to i) identify possible genetic risk markers associated with the development of glaucoma, based on the available literature, and to map their occurrence among members of a three-generation family suffering from glaucoma and multiple autoimmune diseases, ii) find carriers of HLA-DQ2/DQ8 among the members of the same family, iii) verify whether an individual's genotype correlates with his/her phenotype, and iv) determine the potential effect of specific HLA alleles on the glaucoma phenotype. Material and methods: This study used DNA samples derived from 34 members of a three-generation family, in which coeliac...
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Mačinga, Peter. "Patofyziologie chronické pankreatitidy a karcinomu pankreatu." Doctoral thesis, 2019. http://www.nusl.cz/ntk/nusl-405188.
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Chronic pancreatitis is considered a risk factor for pancreatic cancer. An exact mechanism how chronic inflammation of the pancreas leads to pancreatic cancer is not yet understood; the possibility of a shared genetic predisposition for both diseases is also assumed. A similar association in patients with AIP has not yet been demonstrated. The aim of our work was to expand the knowledge about relationship between chronic pancreatitis and pancreatic cancer. We studied the association of the diseases in two synchronous projects. In the first one, we examined the occurrence of pancreatic cancer in patients with autoimmune pancreatitis. In the second project, we investigated the presence of genetics variants associated with chronic pancreatitis in patients with pancreatic cancer. In the retrospective study of our cohort of patients, we were one of the very first in the world to show occurrence of pancreatic cancer in patients with autoimmune pancreatitis, and as the only one, we have defined the characteristics of such patients. To assess the association of the diseases, we performed a systematic review where we identified all reported cases of coincidence of pancreatic cancer and autoimmune pancreatitis; the incidence of cancer in patients with autoimmune pancreatitis was similar to that of patients...
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Mocková, Alice. "Imunologicky riziková žena a její dítě." Doctoral thesis, 2014. http://www.nusl.cz/ntk/nusl-342243.
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Women in childbearing age are often affected by autoimmune diseases (AD) associated with the presence of antiphospholipid antibodies (aPL) that may influence further develop-ment of their children. The primary objective of our prospective study was to determine the presence of the following aPL: anti β2 glycoprotein I (anti-β2GPI), anticardiolipin (aCL), antiphosphatidylserine, antiphosphatidylinositol, antihospha- tidylethanolamine, antiphosphatidylglycerol, antiphosphatidic acid, antiannexin V in mothers with defined AD and their children after birth, at 6 and 12 months of life, and to compare the incidence of aPL with a control group. A secondary objective of the study was a 2-year follow-up of children born to aPL negative and aPL positive mothers with AD in order to detect the possible impact of maternal AD on the health of the offspring. In children, we analysed anthropometric data, blood cell count, cerebral and abdominal ultrasound examination, transient evoked otoacoustic emission test (TEOAE), electrocardiograph (ECG), the presence and kinetics of aPL. At the age of 2 years the Bayley Scales of Infant Development (BSID-II) were used for children's assessment of motor, language and cognitive development. 31 mothers from the total examined 82 aPL positive women with AD delivered 34 neonates...
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Hudec, Michael. "Epigenetická regulace genů HLA asociovaných s celiakií." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-367819.
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Introduction: HLA class II system presents one of the most important mechanism in immune system, which is able to recognise pathogens and damaged cells. Some HLA class II alleles are associated with autoimmune diseases, for example celiac disease, which is typical by chronic inflammation of small intestine and other following symptoms. The risk HLA class II variants are DQ2 and DQ8. Epigenetic mechanisms that regulates gene expression, especially methylation of cytosine in promoter region of DQ2 and/or DQ8 alleles, could have influence on development of T lymphocytes in the thymus, where T-lymphocytes develop and pass a few stages in, and only the survival clones can be part of function immune system. Aim: The aim of this study is to compare methylation level of promoter regions of HLA DQ2 and DQ8 alleles between celiac patients and healthy controls. Another goal is to compare expression level of DQ2 and DQ8 variants between these two groups. Methods: DNA and RNA were isolated from full blood of two sets of donors. DNA was converted by bisulphite conversion and then amplified by Nested PCR. The PCR product was cloned to bacteria. Than positive colonies were selected. Subsequent methylation analysis was performed. RNA was converted to cDNA by Reverse transcription. Relative expression was analyzed...
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Šilha, Martin. "Možnosti využití projektivní metody PFT ve screeningu autoimunitních onemocnění." Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-397904.
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Summary: This diploma thesis deals with the relation between autoimmune processes at biological level (through proven neurological autoimmune disease - multiple sclerosis) and possible autoaggressive processes at the mental level. It is divided into several points. The first one introduces human immunity in general. The first part is followed by immune system description, including autoimmunity and the principle of diseases of this system. Thereafter, psychological aggression is described, in which the division into aggression and auto- aggression fits. This is followed by chapters on projective psychodiagnostics taking into account the detection of various forms of aggression. Then, the thesis focuses on the study of possible auto-aggressive manifestations in patients suffering from the most widespread neurological autoimmune disease, multiple sclerosis. The second half of the thesis describes the author's research on this topic.
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Vobořil, Matouš. "Aire-exprimující buňky v periferních tkáních imunitního systému." Master's thesis, 2014. http://www.nusl.cz/ntk/nusl-337604.
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5 Abstract Tolerance to "self" is the fundamental property of the immune system and its breakdown can lead to autoimmune diseases. In order to eliminate self-reactive T- cells during their development in thymus (central tolerance), Aire promotes the expression of peripheral self-antigens in medullary thymic epithelial cells (mTECs). Recently, Aire was suggested to fulfil a similar function in rare lymph node and spleen cells (peripheral tolerance). However, the detection, characterization and function of these extrathymic Aire-expressing cells is still obscure. The main objective of presented thesis was to investigate if Aire positive cells are also present in other lymphoid as well as non-lymphoid tissues. Using two independent mouse transgenic models we identified the Aire-reporter expressing cells in several lymphoid tissues such as Peyer's patches, spleen and bone marrow as well as in one non-lymphoid organ, the lungs. We show here that based on the expression of B220, EpCAM and CD11c markers these heterogenic cells consist of at least five phenotypically distinct subpopulations, and with the exception of those from lungs, all of them are strictly of hematopoietic origin. This study also demonstrates that Aire on protein level is predominantly expressed by one of these subpopulations with CD45+ MHCII+...
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Jandová, Romana. "Studium interleukinu 37 a jeho role u revmatoidní artritidy." Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-351408.
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Dysregulation between pro- and anti-inflammatory cytokines activity in rheumatoid arthritis (RA) contributes to immune dysregulation, chronic inflammation and subsequent joint destruction. Interleukin-37 (IL-37) has been described as an anti-inflammatory cytokine in several autoimmune diseases. The main aim of this work was to determine the levels of IL-37 in serum and synovial fluid (SF) of RA patients and to compare them with the levels in patients with osteoarthritis (OA) and further explore the association of IL-37 with disease activity and other clinical parameters. Subsequent goal was to study its anti-inflammatory function on RA synovial fibroblasts and describe other cells types of synovial tissue contributing to its production. IL-37 levels were detected using enzyme-linked immunosorbent assay (ELISA). Synovial fibroblasts were stimulated by lipopolysaccharide (LPS) and recombinant IL-37 (rIL-37). The levels of studied genes were detected by PCR. Synovial tissues and immune cells were visualized by immunohistochemical and by immunofluorescence staining. We found increased levels of IL-37 in SF of patients with RA in comparison to OA patients. There was a significant correlation between serum and SF levels of IL-37. RA as well as OA patients showed increased levels of IL-37 in serum than in...
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Čornejová, Lucia. "Prevence autoimunitních chorob." Master's thesis, 2006. http://www.nusl.cz/ntk/nusl-271849.
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he topic of his thesis prevention of autoimmune diseases I selected on the basis of their interest in this issue. They are diseases which are widespread in the population, with a frequency of 5%, and many of them lead to disability and severe restrictions on the affected patients, which have a far-reaching socio-economic impact on our society.
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Krátký, Jan. "Tyreoidální autoimunita a elasticita tyreoidálních uzlů-vztah k jejich biologické povaze." Doctoral thesis, 2019. http://www.nusl.cz/ntk/nusl-405943.
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Thyroid nodules represent a very common pathology. Using modern high-resolution ultrasound, nodules could be found in up to 68 % of patients. The most important task is the diagnosis of thyroid cancer which represents only about 5-15 % of nodules, however the incidence is still growing. Even with the use of a fine needle aspiration biopsy, it is not always possible to decide on the biological nature of the nodule. A significant proportion of such patients have to undergo thyroid surgery for diagnostic reason. Thyroid surgery is associated with risks to the patient and financial costs to the health-care system. In recent decades, the efforts to improve non-invasive diagnostics of thyroid nodules have been made. The thyroid elastography and thyroid autoimmunity are among the examined risk parameters. Using real-time strain elastography, thyroid carcinomas elasticity has been significantly reduced compared to benign thyroid nodules in our group of patients. The elastography of thyroid nodules can be used as a suitable complement to conventional sonographic examination. In our work, the combination of both methods (conventional ultrasound and elastography) increased the negative predictive value compared to both methods individually. The results of our work further indicate that, in case of absence of...
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Kološtová, Katarína. "Imunogenetická studie o autoimunitním diabetes mellitus." Doctoral thesis, 2007. http://www.nusl.cz/ntk/nusl-287949.
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Immunogenetic studies on autoimmune diabetes. Aims of the study: The study has to characterize the genetic background of patients with different types of diabetes mellitus (T1D in children, T1D in adults, LADA, T2D, MODY). The relationship of the diabetes associated HLA-DRB1*04 and NFKB1 genes to the disease course was proved further in the functional studies of the mRNA gene expression. Patients were divided into the tested subgroups in relation to the HLA class II, NFKB1, and NFKBIA genotypes and disease type (T1DM in children, T1DM in adults, and LADA). Results and Conclusion: According to our findings we can conclude that the progression of the diabetes in T1D adults, T1D children and LADA is strongly influenced by different immunogenetic background modifying the ethiopathogenesis of diabetes in the above described groups. Our results offer new possibilities for the population risk testing and may be that far used in the future for better diagnostics of the diabetic's adults.
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Čásová, Miroslava. "Ovlivnění hladiny nejpoužívanějších nádorových markerů a jejich intepretace (ovlivnění systémovými a zánětlivými onemocněními)." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-352945.
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Interpretation of Common Used Tumor Markers Affected by Systemic and Inflammatory Diseases Introduction: An examination of tumor markers is often made as a basis for the successful diagnosis and follow-up treatment of patients with malignant tumors. However, are tumor markers truly significant by themselves, or are they just a baseline quantitative expression of value that we use to diagnose a patient as better or worse based on it increasing or decreasing value? Objective: This paper attempts to answer the question of what factors can affect serum protein and mucin markers and thus lead to a misinterpretation of their results. Methods: Tumor markers were determined by isotopic and non-isotopic laboratory analysis methods, using operational protocols of the immunoanalytic laboratory. All methods were checked using internal quality control, and four times a year using an external quality control. Additionally, 16 236 samples were analysed using 3180 probands during the period 2008-2014. Results: We discovered that in premenopausal women, the markers AFP, CA 125 and HE 4 rise during ovulation peak periods while other markers changed minimally or not at all. However, in postmenopausal women, we proved the incidence of a false positivity marker. With women in the 1st and 2nd trimester of pregnancy, the...
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Bernot, Martin. "Literární přehled pokusů o prevenci autoimunitních onemocnění." Master's thesis, 2009. http://www.nusl.cz/ntk/nusl-273127.
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The final exams of Preventive Medicine in the Master General Medicine is the development and presentation of the thesis.I chose the topic of the thesis "A review of literature attempts to preventautoimmune disease "in the field of autoimmunity, which is interesting and not entirely probádaným phenomenon. In this work, I tried to focus on the interesting findings from the search the field of autoimmunity. Closer I worked rheumatoid arthritis and possible secondary preventive and therapeutic approaches for this disease, because it is the most common autoimmune diseases.
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Pekáriková, Aneta. "Kalretikulin - autoantigen u autoimunitních a nádorových onemocnění." Master's thesis, 2007. http://www.nusl.cz/ntk/nusl-373956.
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Vargová, Lenka. "Imunointervenční terapie nově vzniklého autoimunitně podmíněného diabetu u NOD myší." Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-348930.
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Introduction: Type 1 diabetes mellitus is a chronic metabolic disease caused by autoimmune destruction of pancreatic beta cells. The theory of the disease onset is derived from study of a disease course in non-obese diabetic (NOD) mice, in which the diabetes occurs due to a dysregulation of the immune system. Experimental and clinical studies showed that the autoimmunity may be abrogated by immune intervention, which if initiated early enough may at least slow down the ongoing beta cells lost and preserve residual insulin secretion. But immune intervention alone is not sufficient to restore normoglycemia in the majority of cases. Several interventional studies showed that stimulation of proliferation and/or regeneration of beta cells are necessary to restore normoglycemia in animal models. Aim of the study: To find out, if the combination of a potent immunosuppression (murine anti-thymocyte globulin (mATG), gusperimus) together with stimulation of islet regeneration (sitagliptin) will be able to slow down or reverse the course of the disease. Another aim is to identify the mechanism by which the substances act. Material and methods: All experiments were performed in female NODShiLtJ (H2g7 ) mice. The following parameters were examined at day 0, 7, 14 and 28: blood glucose, subpopulations of...
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Růžičková, Šárka. "Genetické, humorální a buněčné faktory rozvoje autoimunitních chorob." Doctoral thesis, 2010. http://www.nusl.cz/ntk/nusl-296104.
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Autoimmune diseases currently represent the most serious medical issues, mainly due to generally increasing number of patients with these diseases. Their pathogenesis is likely caused by hereditary factors, cellular and humoral interactions influenced by external environmental factors, whose knowledge is important both for diagnostics and therapy, and for theoretical immunology. The aim was to examine the correlation between genetic alterations and the production of autoantibodies, clinical manifestation of the disease; to identify joint autoantigens, further to demonstrate development of leukemic cells from originally autoreactive B cells, the role of B lymphocytes in the pathogenesis of the disease and finally to develop a method for detection of B cells recognizing a defined autoantigen. Several predisposing polymorphisms were revealed using genetic analysis however, they were not exclusively associated either to clinical forms of the disease or usable as prediction markers. In addition, the frequency of alleles IL-1RN * 2 and PD3.1 showed ethno- geographical differences and a critical role of size of sample cohorts in assessing of significance of particular polymorphism was demonstrated in GWA studies. The combination of examination of anti-CCP and IgM RF was found as the best and most...
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Kunteová, Kateřina. "Paralelní detekce virových agens v patogenezi autoimunitních onemocnění." Master's thesis, 2018. http://www.nusl.cz/ntk/nusl-380342.
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Next generation sequencing, which allows concurrent parallel sequencing of many samples and makes it possible to distinguish the infection from multiple viral types in the sample, is well suited as a detection format for such assays described below. The aim of the thesis was to develop a method that could detect all known types of human adenoviruses, human enteroviruses, and bacteriophages selected for their presence in the intestine. Using the next- generation sequencing. The first step was to design primers capable of detecting all known types of viruses, covering the area that is capable of distinguishing these viruses. This method was tested on a set of 47 human adenovirus samples and 30 human enterovirus samples of known serotype. Samples with two serotypes in different proportions were also created. After amplification of the target genome, the samples were purified and sequenced on MiSeq, Illumina. The method was further used in the typing of adenoviruses, enteroviruses and bacteriophages in pre-diabetic cohorts of DIPP, MIDIA, and a cohort of diabetics from African and Asian countries. The tested sample was RNA / DNA isolated from the stool specimen. We have demonstrated that the method is capable to detect all tested virus types, including infections with two different types, even if the...
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Sýkorová, Aneta. "Vyhledávání a hodnocení závažnosti endoteliální dysfunkce u dětí s chronickým autoimunitním onemocněním." Doctoral thesis, 2019. http://www.nusl.cz/ntk/nusl-396317.
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We aimed to evaluate the endothelial function by combining RHI measurements and specific biochemical markers in the children with possible risk of premature manifestation of atherosclerosis and in the control group of healthy children. In all, 124 children (of which 106 patients divided into five groups according to diagnosis - type 1 diabetes mellitus, Crohn's disease, cystic fibrosis, familial hypercholesterolemia and acute lymphoblastic leukemia and 18 healthy controls) were enrolled in the study. During the study, we measured RHI using a new plethysmographic method and further evaluated biochemical markers of endothelial dysfunction (ADMA, E-selectin, hsCRP and VCAM) and lipidogram in individual groups of children. The primary objective of our study was the determination of RHI and biochemical parameters in healthy subjects and in selected risk groups of children (type 1 diabetes mellitus, Crohn's disease, cystic fibrosis, familial hypercholesterolemia and children after successful treatment of acute lymphoblastic leukemia). At the same time, we compared patients from individual groups with the control group. We found significantly elevated RHI values in groups of children with type 1 diabetes, Crohn's disease, cystic fibrosis, and children after successful treatment of acute lymphoblastic leukemia....
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Fundová, Petra. "Slizniční imunita v nemocech horního respiračního traktu a autoimunitních onemocnění." Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-353440.
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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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Brabec, Tomáš. "Nové mechanismy T buněčně zprostředkované střevní autoimunity proti Panetovým buňkám." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-367774.
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(En) Paneth cells are one of the major player in the maintenance of the homeostatic relationship between intestinal microbiota and the immune system. This function is largely achieved by their production of bactericidal enteric α-defensins (ED) and other antimicrobials. Disruption of Paneth cell functions is associated with severe human disorders such as Crohn's disease (CD) and Autoimmune Polyendocrinopathy- Candidiasis-Ectodermal Dystrophy (APECED). However, there is only a very limited information regarding the interactions and regulatory circuits operating between Paneth cells and intestinal immune system in either health or under pathological conditions. The previous study conducted in our laboratory described a new mechanism for the initiation and maintenance of Paneth cells targeted autoimmunity. The suggested model was that ED-specific T cells escape the selection in the thymus, infiltrate the intestine and diminish Paneth cell numbers through autoimmune destruction. This process also lead to the accumulation of inflammation- inducing bacteria, which were implied to exacerbate the inflammatory autoimmunity. Since this model of intestinal autoimmunity is of correlative nature, its intrinsic mechanism and functional relationships between immune system, Paneth cells and microbiota are largely...
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Hadži, Nikolov Dimitar. "Optimalizace metodického repertoáru určeného pro laboratorní diagnostiku autoimunitních onemocnění štítné žlázy." Doctoral thesis, 2006. http://www.nusl.cz/ntk/nusl-268659.
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Janíčková, Žďárská Denisa. "Vztah autoimunity a cytokinů ke klinickým aspektům diabetu mellitus 1. typu." Doctoral thesis, 2007. http://www.nusl.cz/ntk/nusl-287412.
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Čepek, Pavel. "Epigenetická regulace HLA genů II. třídy a jejich role u autoimunitních onemocnění." Doctoral thesis, 2017. http://www.nusl.cz/ntk/nusl-372347.
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(EN) Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with HLA (human leukocyte antigen) class II genes, including HLA-DQA1 gene. Our aim was to investigate DNA methylation of HLA-DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA-DQA1 allele expression of T1D patients and healthy controls. DNA methylation is one of the epigenetic modifications, that regulate gene expression and is known to be shaped by the environment. 61 T1D patients and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulfite and HLA-DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA-DQA1 promoter alleles was analyzed. Individual mRNA HLA-DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA-DQA1 allele 02:01 expression (PPIA normalization, Pcorr=0.041; DRA normalization, Pcorr=0.052) between healthy controls and T1D patients. The complete methylation profile of the HLA-DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in T1D patients and healthy...
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Šimůnková, Kateřina. "Funkce nadledvin u autoimunitního diabetes mellitus typu 1 mladých dospělých (young adults)." Doctoral thesis, 2009. http://www.nusl.cz/ntk/nusl-275759.
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Background: The Addison disease of the autoimmune etiology is mostly appearing as a part of APS2 whereas the most dangerous is a combination of DM1 and an autoimmune adrenalitis. The first evidence of adrenal insufficiency in DM1 is a repetitive hypoglycaemia and lower insulin consumption. Changes in the HPA axis caused by either the activation of the immunity system during the APS2 or by the structural changes in the insulin binding proteins may present the basis for the subclinical adrenal insufficiency. The functional adrenal disorders without autoimmune adrenalitis are frequently observed in autoimmune diabetes mellitus. (...) Conclusions: A rather slow autoimmune adrenalitis progress is observed in adult patients with autoimmune endocrinopathies but rarely ending with a full adrenal destruction. The adrenal antibodies importance is still under study. Higher adrenal disorder count in DM1 patients with first manifestation around the age of 30 is presumed according to our results. Subclinical adrenal insufficiency is still very difficult to diagnose and new diagnostic ways 7 are recently being proposed. We have proven the advantages of salivary cortisol during the test as well as in daily profile. We have shown that adrenal disorders are not caused by cortisol binding peptide structure modifications in...
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Čepek, Pavel. "Epigenetická regulace genů HLA II. třídy a jejich role u autoimunitních onemocnění." Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-306674.
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Abstract Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Its incidence in Europe is continuously rising. The highest T1D risk is associated with HLA (human leukocyte antigen) class II genes. HLA class II molecules play a key role in regulation of immune response. They contribute to the selection of T cell repertoire by presenting antigenic peptides to the CD4+ T lymphocytes. HLA class II expression is controlled by regulatory module that is situated 150 - 300 base pairs upstream of the transcription- initiation site in all HLA class II genes. Polymorphisms in this region are linked to some autoimmune diseases. There were identified several promoter alleles (named QAP) in the HLA DQA1 gene promoter region. Most of the polymorphisms appear to be conserved within haplotype. Individual QAP alleles may have a different promoter strength by which they influence expression of HLA DQA1 gene alleles. Promoter strength can be modulated by DNA methylation. Aims:Our aim was to define methylation profile of HLA DQA1 promoters and determine the mRNA expression of individual alleles of HLA DQA1 gene in T1D patients. The mRNA expression level of HLA DQA1 gene alleles was determined using quantitative PCR. Methods: 30 diabetic pacients (age range 21 to 76 years), were included in this pilot...
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Modrá, Marta. "HLA typizace, autoprotilátkový profil a role mutací v genu pro hemochromatózu u nemocných se systémovým autoimunitním onemocněním." Master's thesis, 2007. http://www.nusl.cz/ntk/nusl-373691.
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Chadimová, Tereza. "Do regulatory T cells reduce the risk of autoimmune pathology induced by CD8+ T cell?" Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-405998.
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5 Regulatory T cells (Tregs) are essential for the maintenance of peripheral self-tolerance and prevention of autoimmunity by suppressing the response of self-reactive CD8+ and CD4+ T cells. However, while interactions of Tregs with CD4+ T cells have been extensively studied, their effect on the self-tolerance of CD8+ T cells has not been explored in detail. The main aim of this diploma project was to provide evidence whether and how Tregs prevent autoimmunity induced by CD8+ T cells. We used an experimental mouse model of autoimmune diabetes allowing us to acutely deplete Tregs and titrate the number of self-reactive T cells, self- antigen affinity, and self-antigen doses. We found out that Tregs play an important role in the prevention of CD8+ T-cell mediated autoimmunity. Moreover, we revealed that Tregs suppress both high-affinity T cells that escape negative selection and relatively weakly self-reactive, but numerous, positively selected T cells. Tregs do so by increasing requirement for the number of self-reactive CD8+ T cells required for the autoimmunity induction. Intriguingly, presence of Tregs does not impact threshold for self-antigen. Moreover, for the first time, we showed that Tregs can suppress CD8+ T-cell-mediated autoimmunity in the absence of conventional CD4+ T cells. This means that...
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Sánchez, Daniel. "Autoprotilátky proti kalretikulinu u pacientů s dilatační a hypertrofickou kardiomyopatií." Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-348666.
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Distinct cellular level of the Ca2+ binding chaperone calreticulin (CRT) is essential for cardiac development and postnatal function. However, CRT is also a potential autoantigen eliciting formation of antibodies (Ab), whose role is not yet clarified. Immunization with CRT leads to cardiac injury, and overexpression of CRT in cardiomyocytes induces dilated cardiomyopathy (DCM) in experimental animals. Hence, we analysed levels of anti-CRT Ab and calreticulin in the sera of patients with idiopatic DCM and hypertrophic cardiomyopathy (HCM). ELISA and immunoblot using human recombinant CRT and Pepscan with synthetic, overlapping decapeptides of CRT were used to detect anti-CRT Ab. Significantly increased levels of anti-CRT Ab of IgA (P<0.001) and IgG (P<0.05) isotypes were found in patients with both DCM (12/34 seropositive for IgA, 7/34 for IgG) and HCM (13/38 seropositive for IgA, 11/38 for IgG) when compared with controls (2/79 for IgA, 1/79 for IgG). Titration analysis in seropositive DCM and HCM patients documented anti-CRT Ab detected at 1/1600 dilution for IgG and 1/800 for IgA (and IgA1) and at least at 1/200 dilution for IgA2, IgG1, IgG2 and IgG3. Pepscan identified several immunogenic CRT epitopes: EVKIDNSQVESGSLED, IDDPTDSKPE, DKAPEHIPDPDA and RKEEEEAEDKEDDAEDKDEDEEDE recognised by IgA and...
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Zedníková, Barbora. "Úloha střevního mikrobiomu v imunitních onemocněních centrálního nervového systému." Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-351469.
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Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Bc. Barbora Zedníková Supervisor: Doc. MUDr. Josef Herink, DrSc. Title of diploma thesis: The role of the gut microbiome in immune-mediated CNS disorders Human body hosts a large number of microorganisms - i.e. Archea, Eukarya, Bacteria and viruses. These microorganisms form microbiome, the total number of the microorganisms is ten times higher than the number of all human cells. Largest part of the microbiome is located in the intestine. The current development of molecular genetics revealed the close relationship between intestinal microbiome and health. Recent studies the most recent studies have pointed to a connection with the pathogenesis of various diseases. This dissertation is focused on the connection between intestinal microbiome and autoimmune diseases of the central nervous system. Research shows that the key factor are the ongoing changes in the composition of microbiome. These changes lead to increased immune stimulation and thereby to inflammatory proliferation.
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Fojtíková, Markéta. "Imunogenetické a hormonální predispoziční markery systémových revmatických onemocnění,zejména systémového lupus erythematodu." Doctoral thesis, 2011. http://www.nusl.cz/ntk/nusl-311490.
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Fojtikova 2011 INTRODUCTION: Several factors like genetic susceptibility is required for systemic rheumatic diseases development. Immunomodulatory PRL effect supports autoimmunity. AIMS: 1. To detect the immunogenetic background (alleles HLA class I, II and microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene) of SLE and PsA. 2. To detect PRL serum and synovial fluid with regard to clinical and laboratory RA activity. 3. To find the role of the functional polymorphism -1149G/T SNP PRL of extrapituitary promoter of PRL gene in SLE, RA, PsA, SSc and inflammatory myopathies development. METHODS: Genetic analyses of pateints with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47) a DM (n=68) and 123 healthy individuals: PCR-SSP (HLA clase I and II), PCR-fragment analysis (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). In 29 RA a 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. RESULTS: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in Czech population. In SLE versus controls allele MIC-A5.1 was increased (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 increases the risk for SLE development, pc <0.000001; OR 9.71....