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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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Molecular mechanisms of cfDNA effects
Hříbková, Natálie ; Daňková, Pavlína (advisor) ; Škubica, Patrik (referee)
The biological role of free circulating DNA is currently being investigated mainly in terms of the etiology of autoimmune conditions and cancer. It appears that the role of cfDNA of nuclear or mitochondrial origin in interacting with receptors of the innate immune system is quite complex and cfDNA is thus involved in a variety of molecular mechanisms such as the spread of cancer metastasis, induction of autophagy and triggering of inflammatory processes. Knowledge of the specific pathways in which cfDNA is involved in the development of these pathologies seems to be crucial, especially in terms of selecting and targeting appropriate therapies. This paper provides a framework for the knowledge on the interaction of cfDNA with receptors of the innate immune system, the induction of immunological signaling pathways and the possible consequences that these molecular pathways may have in the body. Key words: cfDNA, TLR9, cGAS/STING, AIM2, autoimmune disease, biomarker, cancer
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Vitamin D and its functions
De Brito, Christina ; Kočovský, Pavel (advisor) ; Máčová, Ludmila (referee)
Vitamin D is known for its role in the regulation of the metabolism of minerals in the body. Its deficiency is mainly associated with rickets and osteomalacia, characterized by defects in bone growth and development. However, the limits of this hormone's action extend much further. It can influence the differentiation of immune cells, thereby regulating the immune response and cell proliferation. After the discovery of its immunoregulatory functions, vitamin D became a hot candidate for the treatment of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, or diabetes mellitus. Furthermore, vitamin D was found to exhibit a suppressive effect on cancer cells. Vitamin D deficiency is a risk factor associated with the development of encephalomyelitis, schizophrenia, autism, and cardiovascular diseases. Currently, vitamin D analogs are being developed that are just as effective but do not affect calcium metabolism, thus eliminating the toxic effect of high doses of vitamin D. Key words: vitamin D3, 25-hydroxyvitamin D3, 25(OH)D3, cholecalciferol, 1α,25-dihydroxyvitamin D3, 1,25(OH)2D3, calcitriol, immunity, immunoregulatory function, vitamin D deficiency, autoimmune disease
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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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Case Study of Physiotherapy Treatment of a Patient with Diagnosis Guillain-Barré syndrom
Martinovičová, Miriam ; Nováková, Tereza (advisor) ; Kučerová, Ilona (referee)
Thesis title: Case Study of Physiotherapy Treatment of a Patient with Diagnosis Guillain-Barré syndrome. Author: Miriam Martinovičová Supervisors: PhDr. Tereza Nováková, Ph.D Aim: To examine and better understand the autoimmune disease - inflammatory demyelinating polyradiculoneuropathy, and the subsequent rehabilitation care. Methods: Thesis consists of two parts - a theoretical part and a case study. The subject of the case study is a 53-year-old male patient who has inflammatory demyelinating polyradiculoneuropathy. The case study is composed of the anamnesis of the patient, initial kinesiological examination, final kinesiological examination, and therapeutic procedures the patient underwent. The theoretical part contains basic theoretical knowledge, such as the epidemiology, origin, clinical picture, diagnostic methods, treatment options, including GBS rehabilitation options. The patient showed improvements after the therapy program. The aim of this thesis has been achieved. Keywords: Inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome, Autoimmune disease, Physiotherapy
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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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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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