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Immunomodulatory properties of helminth-produced molecules and their effect during autoimmune and chronic inflammatory diseases
Moravcová, Johana ; Šmídová, Barbora (advisor) ; Kolářová, Iva (referee)
Parasitic helminths produce excretion/secretion products (ESP) that affect the host's immune system to prevent damage or exclusion of the parasite. In recent decades, individual ESP molecules have been the focus of research for the treatment of autoimmune and chronic inflammatory diseases due to their immunomodulatory potential. Diseases that have been investigated in this context include ulcerative colitis, multiple sclerosis, type 1 diabetes, rheumatoid arthritis and allergic asthma. Among the pleiad of helminths and their immunomodulatory molecules, it is worth mentioning Acanthocheilonema viteae (Av17), Ancylostoma caninum (NIF), Ascaris lumbricoides (Al-CPI), Brugia malayi (BMCys), Clonorchis sinensis (CsStefin-1), Fasciola hepatica (FhHDM-1), Heligmosomoides polygyrus (HpTGM), Schistosoma japonicum (SjCystatin) and Schistosoma mansoni (Omega-1). The main effects of these molecules on the host immune system include affecting the function of dendritic cells and macrophages, influencing cytokine production and reducing the Th1 immune response, which usually leads to alleviation of disease symptoms. Based on the current state of knowledge, it is not yet certain how the molecules will work in treating patients and whether they will have the same effect when administered in the long term. Despite...
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Léčba autoimunitních onemocnění helmintoterapií
STRANKMÜLLEROVÁ, Zuzana
This bachelor thesis will discuss the impact of gastrointestinal helminths on the human immune system concentrating especially on their therapeutical potency in the treatment of autoimmune diseases. Epidemiological studies show a significant difference between developing and developed countries. This inequality gave rise to the two hypotheses: the Hygiene Hypothesis and the Old Friend Hypothesis. These theories mention the fact that exposure to the parasites may lower the risk of developing autoimmune diseases. Anti-inflammatory products of helminths modulate the immune system to induce Th2 response (with rising levels of anti-inflammatory cytokines e.g. IL-4, IL-10 a TGF-). Therefore, helminths or their molecules can cure autoimmune inflammatory diseases or even diseases of civilisation.
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HLA typizace v klinické praxi - využití k testování predispozic k onemocněním autoimunitního typu
VESELÁ, Dominika
Autoimmune diseases require the interplay of internal (genetic) and external (environmental) factors to develop and erupt. The essential genetic factors include HLA alleles, whose carrying is associated with a significant predisposition to the development of a specific autoimmune disease. This Master Thesis deals with the problematics of autoimmune diseases associated with HLA system. The practical part focuses on the examination of predisposing alleles related to celiac disease as one of the most widespread autoimmune disease, which many scientific teams are dealing with, but even in the Czech Republic there are not enough population studies of this disease. Thanks to data from genetic laboratory GENLABS s.r.o. in České Budějovice, ÚHKT and VFN in Prague it was possible to focus on such population study.
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Induction of immune responses by intestinal segmented filamentous bacteria
Pacáková, Iva ; Dobeš, Jan (advisor) ; Schwarzer, Martin (referee)
The intestine is constantly exposed to a variety of pathogens, and therefore a proper function of the intestinal barrier is essential for the overall health of the body. Segmented filamentous bacteria are members of the gut microbiota residing in the terminal ileum of the small intestine, where they penetrate through the mucus layer and tightly associate with intestinal epithelial cells. This SFB association with the epithelium is accompanied by the formation of endocytic vesicles filled with an antigen that triggers the IgA production in the intestine and the Th17 cell dependent immune response. There are two steps for the induction of Th17 cells. First, SFB-dependent induction of Th17 cells requires antigen presentation by MHC class II molecules. Therefore, antigen-presenting cells migrate to the site of induction in mesenteric lymph nodes and prime antigen-specific naive T cells to become RORγt+ pre-Th17 T cells. Secondly, activated T cells migrate back to the lamina propria, where they undergo functional maturation by triggering cytokine production. As a result, Th17 cells accumulate in lamina propria, where they produce their effector cytokines IL-17 and IL-22, further affecting the gut's overall balance. However, the extensive Th17 polarization induced by SFB may subsequently contribute to...
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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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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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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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Mesenchymal stem cells and their effects on regulatory B cells
Smolová, Helena ; Boháčová, Pavla (advisor) ; Stříž, Ilja (referee)
Mesenchymal stem cells (MSC) are multipotent cells with the ability to regulate reactivity of cells of immune system. Regulatory B cells (Bregs) are also capable of modulating immune responses. Both these cell types are able of creating anti-inflammatory and tolerogenic environments and represent potential of cell-mediated therapy for autoimmune diseases and transplantation reactions. The effect of MSC on Bregs activation and function has been only studied in recent years, and mechanisms of their effects are not yet well characterized. However, studies have demonstrated a decrease in effector B lymphocytes and antibody production, and a support of activation of Bregs subpopulation and increased production of anti-inflammatory interleukin 10. Various molecules produced by MSC are involved in Bregs induction. Unfortunately, their effects have not yet been sufficiently described, and different models yields diverse results. In addition to the current studies in experimental models, the first clinical trials on Bregs have been initiated. The positive results suggesting the potential for future use of Bregs for the treatment of autoimmune diseases and transplantation reactions have been obtained in both cases. Key words: regulatory B cells, mesenchymal stem cells, immunomodulation, autoimmune diseases,...
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