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Epigenetické regulace u autoimunitních onemocnění se zaměřením na revmatoidní artritidu
Horková, Veronika ; Daňková, Pavlína (advisor) ; Hušáková, Markéta (referee)
Exact cause of rheumatoid arthritis, as well as other autoimmune diseases has not been identified yet. In last twenty years, epigenetics showed a new face of immune system. DNA methylation, modification of histones - proteins around which DNA is wrapped, or interference of small RNA sequences - microRNAs, these all are heritable changes outside the DNA sequence that provide another component involved in autoimmunity. Presented epigenetic mechanisms alter gene expression and thus facilitate production of pro- inflammatory factors leading to autoimmune reactions. Moreover, genes regulating apoptosis are also frequently targeted by epigenetic modifications. Not only these mechanisms provide another level of immune defense, they also explain higher female susceptibility to autoimmune diseases and the influence of environment on pathogenesis of these diseases.
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Dendritic cells and autoimmune diseases with a view to type 1 diabetes mellitus
Chrástová, Iveta ; Štechová, Kateřina (advisor) ; Krulová, Magdaléna (referee)
Dendritic cells (DC) are professional antigen-presenting cells (APC) that play an essential role in the induction of immune responses. DCs develop from CD34+ hematopoietic stem cells in bone marrow and their role is uptake, processing and presentation of antigens to T cells. DCs can be divided into two distinct subset of cells, myeloid a plasmacytoid DCs. Myeloid DCs (mDC) develop from hematopoietic cells in the presence of GM-CSF and TNF-α or from monocytes in the culture with GM-CSF and IL-4, then with CD40L they mature and produce a large number of IL-12, which is important in driving CD4+ T cell to type Th1. The development of pDC is CD40L and IL-3 dependent and Flt3-L supports this process as well. The essential role of pDC is that they secrete a large amounts of type I IFN in the responses to viruses and so they maintain the antiviral stage. To recognize the viruses pDC express Toll-like receptors 7/9. DCs have on the surface also other groups of receptors, e.g. C-type lectin-like receptors, RIG-I-like receptors and NOD-like receptors. They play the role in the various diseases, mostly autoimmune diseases, in which the immune system recognizes self tissues and activates against them the immune response. Dendritic cells function is that they are competent to activate T cells, in the most cases...
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B-1 lymphocyte population and their role in the development of autoimmune diseases
Jabůrek, Filip ; Hájková, Michaela (advisor) ; Kalous, Martin (referee)
B-1 lymphocytes are specific type of B cells, development of witch occurs primarily in neonatal period of life. Later, the population is maintained through self-renewel. B-1 lymphocytes differ from classic folicular B lymphocytes in development from a distinct progenitor, expression of specific surface markers and production of polyreactive natural immunoglobulins. Since the discovery linking B-1 lymphocytes to the development of autoimmune diseases there was a shift in perspective on the B-1 lymphocytes and revaluation of the known facts. The aim of this thesis is to present a summary of current knowledge about B-1 lymphocytes, mechanisms of their effect on the development of autoimmune diseases and to outline the possible application of these findings in therapeutical practice. Key words: B-1 lymphocytes, autoimmune diseases, lupus, leukemia, SLE, B-CLL
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Study of interleukin 37 and its role in rheumatoid arthritis
Jandová, Romana ; Šenolt, Ladislav (advisor) ; Krulová, Magdaléna (referee)
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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Case study of physiotherapy treatment of patient with diagnosis systemic lupus erythematosus
Mrázková, Tereza ; Nováková, Tereza (advisor) ; Taušová, Eva (referee)
Title: Case study of physiotherapy treatment of patient with diagnosis systemic lupus erythematosus Objective: A summary of theoretical background, study of comprehensive rehabilitation methodology, proposal of therapy and evaluation of its effect in a patient with diagnosis systemic lupus erythematosus. Methods: The Review of literature and the case study were made during practice in Institute of Rheumatology in Prague from 5. to 30. 1. 2015. It is devided into two parts. Theoretical part summarizes definition, etiology, epidemiology, diagnostics, clinical manifestation, therapy and use of physiotherapy in diagnosis systemic lupus erythematosus. The case study is presented in the special part. Therapeutical approach was prescribed according to the medical history and physical examination and its effect was assessed using kinesiology analysis at the end of the study. Results: The pain of the patient substantialy decreased, she has no more breathing problems and lying in horizontal position is also no longer a problem, the quality of sleep enhanced, the body posture and balance were positively enfluenced and range of motion and stabilization ability of spine improved. Therapeutic methods were chosen appropriately and stated goals of physiotherapy were fulfilled. Keywords: systemic lupus...
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Th17 lymphocytes and autoimmunity diseases with the intention of diabetes 1. type
Labiková, Jana ; Štechová, Kateřina (advisor) ; Procházková, Jana (referee)
Th17 cells were recently identified as a cell source of IL-17. They turned up to be a T cell lineage independent of previously described Th1 and Th2. The differentiation of naive CD4+ T cells towards Th17 requires the combination of TGFβ (a cytokine essential for the development of anti-inflammatory regulatory T cells) plus IL-6 or IL-21. IL-23 is required for in vivo function and phenotype maintenance of Th17. STAT3 and RORγt were identified as pivotal transcription factors in Th17 differentiation program. Th17 proved to have pro- inflammatory effects and are characterized by the production of IL-17A, IL-17F and IL-22 - cytokines implicated in host defense against certain extracellular pathogens. The cytokine products of Th17 cells act on wide range of cell types. They induce cytokines, chemokines and metalloproteinases and they also mediate neutrophil recruitment and production of antimicrobial peptides. Autoreactive Th17 are highly pathogenic and the production of IL-17 has been detected in several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, Crohn's disease and type 1 diabetes. These diseases were thought to be mediated by Th1 cells, but it is becoming increasingly clear that the regulation of autoimmunity is influenced at least in some diseases by Th17 cells as well.
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Interpretation of Common Used Tumor Markers Affectedy by Systemic and Inflammatory Diseases
Čásová, Miroslava ; Topolčan, Ondřej (advisor) ; Ludvíková, Marie (referee) ; Šafarčík, Kristian (referee)
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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The role of microbiome in celiac disease
Tučková, Kateřina ; Konečná, Klára (advisor) ; Jílek, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Subject of study: Healthcare bioanalytics Student: Kateřina Tučková Supervisor: RNDr. Klára Konečná, Ph.D. Title: The role of microbiome in celiac disease Background: Descriptions of the celiac disease problematics. Focus on the origin of the disease and its possible connection and role of the intestinal microbiome. Define the term microbiome and point out its possible role in human health. Finally, address the attention to possibilities in the treatment of celiac disease. Main findings: The role of the microbiome in celiac disease and other diseases is a frequently discussed topic. Patients with the celiac disease diagnosis depend on a lifelong gluten-free diet. The microbiome is highly specific to and is affected by many external stimuli, which can often be affected. Current studies point to a linkage between the microbiome and many diseases, including celiac disease. Conslusions: More knowledge is needed for the complex insight into the problematics of the relationship between celiac disease and the microbiome. In general, the microbiome composition has a much more significant impact on human lives than previously thought. Intestinal microbiome imbalance is related to celiac disease...
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Comorbidity of psychical and autoimmune diseases
Kaňková, Zuzana ; Šolc, Roman (advisor) ; Mravec Bencúrová, Dominika (referee)
Mental and autoimmune disorders represent a wide range of different diseases and are currently one of the most common health problems. In recent years, a significant association between these two types of disorders has been observed, supported by both their frequent coexistence and other important findings such as shared genetic risk factors, the discovery of neuronal surface antibodies or immune system changes related to some mental disorders. This work attempts to map the autoimmune diseases that occur more often or rarely in patients with various mental disorders (and vice versa) and also describes possible mechanisms that may play a significant role in the development of this phenomenon. Key words mental disorders, autoimmune diseases, comorbidity, etiology, epidemiology, shared risk factors
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Maternal and fetal microchimerism.
Hynková, Marie ; Tlapáková, Tereza (advisor) ; Pačes, Jan (referee)
Microchimerism is defined as the presence of small amount of genetically distinct cells in one individual. It most often arises during pregnancy and breastfeeding. It can also arise from blood transfusion or organ transplantation. During pregnancy there occurs a bidirectional migration of cells through the placenta between the mother and the fetus. Cells which are transferred during pregnancy and breastfeeding can persist in the offspring until adulthood. During breastfeeding, a big number of immune cells is transferred to the offspring via mother's milk. These cells protect the offspring against pathogens and are involved in modulation of its immune system. Fetal cells persist in mother organism even decades after giving birth and can have long-lasting effect on mother's health condition. These fetal cells can help to regenerate mother's damaged tissues, but they can also contribute to the development of serious autoimmune diseases.
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