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Modulation of mesenchymal stem cell properties and their use in the regulation of transplantation immunity
Peřinová, Lucie ; Krulová, Magdaléna (advisor) ; Zajícová, Alena (referee)
Mesenchymal stem cells (MSCs) represent a heterogeneous population of stromal cells with a pluripotent differentiation potential. They can be isolated from multiple tissues of mesodermal origin, such as bone marrow, adipose tissue, umbilical cord blood and peripheral blood and afterwards externally expanded according their adherence to the plastic surfaces. These cells show remarkable immunomodulatory properties, suppressing T-, B- and NK-cell functions, and also modulating dendritic cell activities and influencing immune responses during tissue repair and recovery. MSCs have been shown to possess ability to migrate to sites of inflammation and tissue injury. All these properties make MSCs a promising tool for clinical application. Our primary goal was to identify processes that may influence immunoregulatory effects of MSCs. In order to promote immunossupressive qualities of MSCs we established the scheme comprising MSCs precultivated with various cytokines and Toll-like receptors (TLR) ligands in vitro, with the final aim to improve the therapeutic effect of MSCs on wound healing in vivo. We studied modulation of MSCs properties and consequently the effect of influenced MSCs on cells of the immune system. The immunosuppression is mainly mediated through secreted factors that MSCs produced after...
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Regulation of the cytokine IL-33 production and its biological effects.
Kardošová, Miroslava ; Stříž, Ilja (advisor) ; Zajícová, Alena (referee)
IL-33 is a dual function protein that may function as both a proinflammatory cytokine and an intracellular nuclear factor. In a role of cytokine IL-33 signals via receptor ST2 and induces T helper type 2-associated cytokines in its target cells including mast cells, basophils, eosinophils and natural killer cells. Additionally, it acts as chromatin-associated nuclear factor with transcriptional regulator properties affecting expression of some proinflammatory cytokines. Regulation of this processes is poorly understood, mechanisms underlying synthesis, processing and secretion of IL-33 also remain to be fully explored. The aim of our study was to examine mechanisms probably involved in regulation of IL-33 production and its secretion outside the cell. First, we investigated possibility that IL-33 secretion is affected by stimulation with cytokines TNFα, IFN γ, IL-1β, IL-13, IL-33, TGF-β and IL-10 or stimulation with LPS isolated from E. coli. Next we investigated hypothesis that IL-33 is released from cells during cell damage or necrosis and serve as "alarmin". Necrosis was induced in LPS-stimulated cells by freeze-thawing cycles. Besides the presence of IL-33 we tested levels of IL-1α and IL-1β. In our experimental model, we used A549 cell line (alveolar type II-like cells), THP-1 promonocytic...
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Immunologic profile of experimental autoimmune encephalomyelitis
Novosádová, Iva ; Fišerová, Anna (advisor) ; Zajícová, Alena (referee)
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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Evolutionary implications of innate immunity receptors polymorphism
Bainová, Zuzana ; Vinkler, Michal (advisor) ; Zajícová, Alena (referee)
Interactions between hosts and their parasites are considered to be one of the major forces driving animal evolution. It can be assumed that the evolutionary changes will occur especially in host molecules directly involved in these interactions. The first line of host defense is formed by innate immunity receptors among which also pattern recognition receptors (PRRs) belong. PRRs detect the presence of parasites at the beginning of their invasion by binding characteristic structures of their bodies (so called pathogen-associated molecular patterns, PAMPs, e. g. lipopolysaccharide, flagellin or peptidoglycans) or abnormal self molecules (damage-associated molecular patterns, DAMPs, e.g heat shock proteins). Although this mechanism of immune system activation is based on the recognition of ligands that are relatively evolutionarily conservative in pathogens, growing body of evidence suggests that PRRs are highly polymorphic on both interspecific and intraspecific level. High frequencies of minority alleles can be observed in most populations studied. It has been proven that particular alleles of many PRRs may associate with increased or decreased resistance to various infectious or autoimmunity diseases. Relationship between polymorphic receptor and a disease could be the main force, which shapes the...
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The role of T regulatory cells in kidney transplantation
Urbanová, Anna ; Stříž, Ilja (advisor) ; Zajícová, Alena (referee)
T regulatory lymphocytes (Treg) belong to the CD4+ cell group. They are an essential part of the immunity system. Treg cells prevent from excessive activation of effector T cells and they keep the tolerance to the tissues of the body. They have high expression of CD25 and the transcription factor Foxp3. We distinguish two basic populations of Treg cells: natural Treg cells (nTreg) created in the thym and representing 5-10 % of all CD4+ cells, and induced Treg cells (iTreg), created from naive CD4+ cells in the periphery.Their regulatory effect is well-known, therefore using of Treg cells could bring about a huge treatment potential for patients with a transplantated kidney. Healthy people and patients tolerant to the transplantated kidney show higher occurance of circulating Treg cells and the Treg cells present in the graft unlike patients with chronical rejection. The tolerance is cancelled with the damage of CD4+ CD25+ cells.For a graft acceptance it is necessary to treat the patient after the transplantation with immunosuppressive medicaments resulting in suppression of immunity reaction against the graft. Their disadvantages are side effects often resulting in the patient's death. Moreover they often have a negative impact on survival and expansion of Treg cells. The analysis of flow cytometry has...
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Comparison of Immune System of Newborns and Adults
Dusilová, Adéla ; Zajícová, Alena (referee) ; Hrdý, Jiří (advisor)
In general, it is possible to characterize neonatal immune system (IS) as immature in comparison to adult IS. From a clinical point of view, newborns show an increased susceptibility to infections. Breastfeeding can contribute to the descent incidence of illnesses, because it supplies the intestinal mucosal system with antibodies of the mother`s origin, important nutrients and other immunoregulatory components. Breast milk compensates decreased newborn's capacity to produce immunoglobulins- especially IgA, that concentration reaches adult levels in two years, but even later (to the pubescent period). Other classes of antibodies are found in cord blood only sporadically except IgG, which is transferred transplacentary. Reduced ability of B lymphocytes to produce antibodies is caused by insufficient expression of surface costimulatory signals of Th2 cells. T lymphocytes are not able to react properly to low doses of stimulators (polyclonal activators - phytoid lectins: ConA or PHA), which bind to T cell receptors in complex with CD3 and proliferate in a response to anti-CD3 monoclonal antibodies. Most of the cord blood T lymphocytes display "naive" phenotype CD45RA. During intrauterine development, neonatal IS is in contact with mother IS and because a pro-inflammatory Th1 response could lead to...
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