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Tolerogenic dendritic cells as immune interventions in prevention or therapy of type 1 diabetes
Petrovčíková, Diana ; Funda, David (advisor) ; Hrdý, Jiří (referee)
The main aim of this work is to refer a recent summary of the opportunities and pitfalls of the application of tolerogenic dendritic cells in the prevention or therapy of type 1 diabetes (T1D). Tolerogenic dendritic cells (TolDCs) represent a potential tool for the treatment of allergies, transplant rejections and autoimmune diseases, including T1D, due to their capability to specifically inhibit autoimmune reactions without causing general immunosuppression. TolDCs represent a specific group of dendritic cells and are essential in establishing central and peripheral tolerance. This work presents a helpful guide to better understanding the physiology of tolerogenic DCs and an overview of in vitro generation attempts. In addition, the route of application and migration to target organs has been described. Type 1 diabetes (T1D) is a chronic disease resulting from immune-mediated destruction of the insulin-producing beta cells in the pancreas. Animal models have been invaluable in testing innovative medical treatments since the early testing of insulin in dogs almost a century ago. Animal models of type 1 diabetes (T1D) enable the study of the mechanisms underlying its pathogenesis and the potential development of therapeutic interventions. However, there are still significant gaps in our general...
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Dietary habits and their influence on compensation of pregnant women with type 1 diabetes
Mlejnková, Klára ; Krejčí, Hana (advisor) ; Anderlová, Kateřina (referee)
Introduction: This bachelor thesis deals with the dietary habits of pregnant women with type 1 diabetes before and during pregnancy with regard to the diabetes control. It then points the changes in these habits that occurred during pregnancy. Aims: The theoretical part briefly describes the characteristics of type 1 diabetes and its treatment. It then describes pregnancy in this disease and complications of diabetic pregnancy. More attention is paid to nutrition during preconception and pregnancy. It discusses in more detail the various macronutrients and micronutrients needed during these periods and highlights foods and beverages that are inappropriate. The main aim of the practical part was to determine the dietary habits of women with type 1 diabetes before and during pregnancy and then to compare whether these were modified to diabetes control. Methods: The data for the bachelor thesis were obtained by means of a questionnaire survey conducted from August 2022 to April 2023. Two questionnaires were created in the electronic interface of Google Forms and subsequently offered to patients with type 1 diabetes in the outpatient clinic of the Gynaecology and Obstetrics Department of the 1st Faculty of Medicine of the Charles University and the University Hospital. Data from the documentation of...
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Tolerogenic dendritic cells in immunotherapy of type 1 diabetes
Grohová, Anna ; Špíšek, Radek (advisor) ; Černý, Jan (referee) ; Hrdý, Jiří (referee)
Type 1 diabetes is characterized by chronic hyperglycaemia leading to life-threatening complication. The pathogenetic mechanism of T1D is the abnormal immune reaction destroying β-cell mass in pancreas. The current therapy is based on the administration of subcutaneous insulin. However, this therapy can not prevent the episodes of transient hyperglycaemia. Thus, the high blood glucose influences negatively cellular metabolism and progressively leads to tissue damage. The cellular therapy brings the new strategy allowing the direct modulation of the abnormal autoimmune reaction. This strategy promises more targeting therapy with less adverse effects. In this thesis we discuss two types of immune-suppressive cells which are candidates for cellular therapy in autoimmune diseases. The first part describes the tolerogenic dendritic cells (tDC) and their stable suppressive phenotype in proinflammatory condition. tDC maintain their stable inhibitory phenotype and are able to suppress antigen- specific T-cell proliferation together with the induction of T-regulatory cells. These properties of tDC are very important for potential clinical application. The thesis also reveals the relation between laboratory parameters of T1D patients and suppressive properties of tDC. The second part of the thesis is focused...
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Effect of bacterial monoassociations (Akkermansia muciniphila) on development of type 1 diabetes and immune parameters in ex-germ-free NOD mice
Němec, Dušan ; Funda, David (advisor) ; Zadražil, Zdeněk (referee)
Type 1 diabetes (T1DM) is an autoimmune condition affecting around 0,4 % of general population and its prevalence is still increasing. T1DM is a multifactorial disease, and it develops under the forces of various environmental and hereditary factors. Gut microbiota is recently one of the most relevant environmental features of autoimmunity, including T1DM. Healthy gut microbiota is characterized especially by its variability. However, there has been an effort to determine critical bacteria that can either drive or suppress T1DM development. Akkermansia muciniphila is among those potentially protective bacteria. This diploma thesis examined changes of immune parameters, such regulatory T cells, NK cells, γδ T cells and expression of IFNγ, IL-10 and IL-17, and their correlation with T1DM onset in A. muciniphila- monoassociated ex-germ-free NOD mice compared to germ-free (GF) and specific-pathogen- free (SPF) controls. Furthermore, the second part of the thesis, NOD-SCID adoptive transfer provided an insight into whether diabetogenic ability of NOD mice-derived splenocytes differ in A. muciniphila vs GF and SPF controls. Minor differences were found in immune parameters among various cell populations, with the most prominent increased IL-10 expression in A. muciniphila-monoassociated mice compared to...
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Effect of diabetogenic autoantigens on the cytokine production of peripheral blood mononuclear cells from type 1 diabetic patients
Labiková, Jana ; Štechová, Kateřina (advisor) ; Holáň, Vladimír (referee)
5 Abstract Type 1 diabetes (T1D) is a serious organ-specific autoimmune disease characterised by irreversible destruction of pancreatic β-cells by immune system. This process results in an absolute insulin deficiency. Both genetical predisposition and environmental factors influence the development of the disease. β-cell destruction is mediated by cellular components of an immune system. Proinflammatory Th1 response is considered as most pathological. Autoimmune destruction of β-cells can be identified by the detection of specific serum autoantibodies a long time before the T1D clinical onset. Currently, there is no efficient cure available to prevent or at least to delay the destructive insulitis. This diploma thesis describes the influence of synthetic diabetogenic autoantigens GAD65 and IA2 on the cytokine response of peripheral blood mononuclear cells (PBMC) obtained from T1D patients with regards to their antibody profile. The study has been carried out on patients with confirmed T1D diagnosis who tested positive for anti-GAD65 and/or anti-IA2 autoantibodies. By using flow cytometry we measured the cell type ratio in PBMC samples. The cells have been stimulated by three different concentrations of antigens and their IFNγ and IL-17 production has been detected by ELISPOT assay. In the case of both...
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Analysis of hypoglycemia by Continuous Glucose Monitoring in patients with Type 1 diabetes
Hrubantová, Tereza ; Šoupal, Jan (advisor) ; Flekač, Milan (referee)
This bachelor's thesis presents an analysis of type 1 diabetes patients' hypoglycemia using continuous glucose monitoring. The thesis aims to evaluate the occurrence of hypoglycemia, the prevalence of impaired awareness of hypoglycemia and to investigate how patients treat hypoglycemia. The theoretical part of the thesis presents a summary of the general knowledge of type 1 diabetes diagnosis, focusing on the hypoglycemic issues and diabetes compensation improvements using continuos glucose monitoring. The practical part analyses hypoglycemia frequency and duration using continuous glucose monitoring. Occurrences of the impaired awareness of hypoglycemia, as well as the ways in which patients treat hypoglycemia, are evaluated according to a modified Clark Method. The research shows that the actual occurrence of hypoglycemia is significantly higher than its occurrence as perceived by the patients. Continuous one-week blind glucose monitoring shows that hypoglycemia occurs in 85 % of patients at night and 95 % of patients during the day. In total, patients suffered hypoglycemia 7.2 % of the week, i.e. approx. 12 hours, of which 4 hours and 40 minutes occurred at night while 7 hours and 21 minutes they were experiencing hypoglycemia during the day. The impaired awareness of hypoglycemia prevalence...
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Roles of environmental factors and microbiome in type 1 diabetes
Novotná, Kateřina ; Funda, David (advisor) ; Cahová, Monika (referee)
Type 1 diabetes mellitus (T1DM) is an insulin-dependent autoimmune disease. Its onset is characterized by an autoreactive self-destruction of β-cells within pancreatic islets. T1DM is influenced by multiple genetic predispositions, but since the incidence of the disease has increased dramatically in the past decades, especially in developed, western-type countries, the importance of the environmental factors has become obvious. There are various significant environmental influences that need to be addressed in the equation of variables. This bachelor thesis deals with the environmental variables and their mechanisms in T1DM and focuses on several areas of interest. It introduces frequently used spontaneous animal model of T1DM, pathogenetic mechanisms and T-cells in T1DM as well as regulatory immune cells and their mechanisms, in the light of hygiene and another hypothesis. Next it addresses the role of intestinal microbiota, dietary factors, mucosal immunity, their mechanisms and interactions in T1DM and extends to other, less researched, but important environmental variables such as circadian rhythm in connection with circadian gene expression depending on the rhythmicity of light/dark rotation and timing of food intake throughout the day, psychological/oxidative stress, and the effects of...
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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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