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Comparison of Immune System of Newborns and Adults
Dusilová, Adéla ; Hrdý, Jiří (advisor) ; Zajícová, Alena (referee)
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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Comparison of cytokine production by leukocytes from newborns of healthy and allergic mothers
Dusilová, Adéla ; Hrdý, Jiří (advisor) ; Janatková, Ivana (referee)
The increasing incidence of children suffering from allergic diseases could be caused by sensitization of immature immune system during the intrauterine development. Several important scientific papers have demonstrated the ability of cord blood cells to respond by elevated proliferation activity after stimulation by common allergens. Following these findings, present study follows the production of cytokines which play a role in the pro- and anti-allergenic tuning of the immune system. Umbilical cord blood cells were stimulated with polyclonal activators (phytohaemagglutinin) and common allergens (ovalbumin, timothy grass, birch, mite). Subsequently, cytokine production was monitored using selected methods that reflect different stages of cell activation - at the level of mRNA by quantitative real time PCR (qRT-PCR), by flow cytometry detection of the presence of intracellular cytokines in different cell subpopulations and by ELISA measurement of cytokines in CBMC culture supernatants. The results obtained point to a very weak ability of these common allergens (timothy grass, birch, mite, ovalbumin) to stimulate CBMC to produce cytokines observed by all of these methodological procedures. Although we did not observe significant differences in CBMC cytokine production (IL-2, IL-4, IL-10, IL-12,...
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The effect of progesteron administration on T regulatory cells in relation to preterm deliveries
Škvorová, Anna ; Hrdý, Jiří (advisor) ; Krulová, Magdaléna (referee)
During pregnancy, the maternal organism has to cope with the presence of foreign paternal antigens, allow and support the development of a semialogenic fetus, while maintaining its defense against pathogens. This condition is achieved by a dynamic balance of complex immuno-endocrine interactions. A number of cells with specific properties contributes to the tolerogenic setting during pregnancy. Very important role plays the population of T regulatory lymphocytes (Treg). Treg levels increase physiologically during pregnancy and their decline is associated with term and preterm labor. Premature birth is a serious socio-economic problem, affecting around 10 % of births worldwide. In the case of increased risk of premature labor, progesterone administration has been successfully used in clinical practice. One hypothesis says that progesterone induces an increase in Treg population and delays premature labor in this way. The aim of the thesis was to monitor the effect of progesterone therapy in vivo on the amount and functional properties of CD4+ CD25+ FoxP3+ Helios+/- Treg and to verify whether long-term vaginal administration of progesterone positively correlates with an increase in Treg counts. Another goal was to determine whether progesterone promotes Treg generation and the production of...
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IL-25: Novel target to treat allergic diseases
Lišková, Kateřina ; Hrdý, Jiří (advisor) ; Boháčová, Pavla (referee)
Interleukin (IL) 25 is a proinflammatory cytokine that promotes a Th2-type cell response. Its alternate name is IL-17E, and along with 5 other members, IL-25 belongs to to the family of cytokine IL-17. The family is based on the similarity of their amino acid sequences. The source and target cells of IL-25 include many different cell types. IL-25 is not only produced by many types of immune cells, but epithelial and Paneth cells are involved in its production as well. Its receptors form heterodimers composed of 2 subunits - IL-17RA and IL-17RB. Both receptor proteins are required for IL-25 mediated activities and occur in other IL-17 family members. IL-25 also plays an important role in allergies - one of the most common diseases in developed countries. Cytokine IL-25 has been studied primarily in asthma. However, other very common types of allergies, such as food allergies, atopic dermatitis and allergic rhinitis, can not be overlooked. Even in these cases, the role of IL-25 is not negligible and is studied. Based on the knowledge of IL-25 biology and its role in allergies, this cytokine may be an important therapeutic target in the treatment of allergic diseases. One possibility is, for example, the use of neutralizing antibody and subsequent blocking of IL-25 activity. Key words: interleukin-25,...
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The therapeutic potential of mesenchymal stem cells in a mouse experimental model
Hájková, Michaela ; Krulová, Magdaléna (advisor) ; Hrdý, Jiří (referee) ; Šírová, Milada (referee)
Due to their immunomodulatory and regenerative potential, mesenchymal stem cells (MSCs) represent a promising therapeutic tool for cell-based therapy, organ transplantation or tissue engineering. To improve clinical applicability of MSCs, new methods to increase their delivery and efficacy have been tested in the latest years but the mechanism of observed alterations has not yet been described. In the present project we focused on studying the effect of several factors that can significantly affect the therapeutic success of MSC-based treatment. Initially, we analysed the therapeutic effect of MSCs applied locally on nanofiber scaffold with incorporated cyclosporine A (CsA) in a mouse model of allogeneic skin transplantation. Our results indicate that application of MSCs in the presence of CsA direct M1/M2 macrophage polarization towards regulatory phenotype. This phenotype switching is accompanied by decreased production of nitric oxide (NO) and interferon (IFN-) and increase production of interleukin 10 (IL-10), and may result in suppression of the local inflammatory reaction. The next goal of proposed study was to analyse the effect of the treatment based on MSCs combined with immunosuppressive drugs with different mechanism of action on the balance among distinct T cell subpopulations. We...
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Targeted differentiation and transdifferentiation of stem cells and their therapeutic application
Chudíčková, Milada ; Holáň, Vladimír (advisor) ; Bernášková, Klára (referee) ; Hrdý, Jiří (referee)
Mesenchymal stem cells (MSCs) naturally differentiate into cells of tissues of mesodermal lineage: cartilage, bone or adipose tissue. As a result of specific environmental stimuli, MSC are able to transdifferentiate into cells of endodermal or ectodermal lineage. Also, MSCs are able to regulate the inflammatory processes and to support healing and regeneration. These properties make MSCs suitable in cell-based therapy and tissue engineering. Characteristics of MSCs (for example differentiation and proliferative potential and cytokine secretion profile) can vary slightly depending on their origin. These differences can be further amplified by the effects of specific environments. Thus, to obtain maximal benefit, it is important to select MSCs optimal for a particular environment. The main goal of this thesis was to design in vitro protocol for transdifferentiation of MSCs into neuron-like cells. For this application, the adipose tissue-derived MSCs seemed to be optimal, due to their higher production of basic fibroblast growth factor, one of the important factors in neural development. The resulting cells acquired typical neuron-like morphology, expressed genes for neuron-specific markers and produced neuron-specific proteins. Further, the resulting cells showed immunomodulatory properties similar...
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Methods for detection of impaired immune response in cardiac-surgical patients
Kormundová, Nikola ; Koláčková, Martina (advisor) ; Hrdý, Jiří (referee)
In patients after cardiac surgery, there is an increase in the level of molecules with both pro-inflammatory and anti-inflammatory effects. This increase is influenced by the patient's clinical condition, but also by the nature of the operation itself, which uses conventional extracorporeal circulation. This technique leads to damage to blood elements by direct contact with air and parts of the extracorporeal circulation, as well as to ischemia-reperfusion injury. The specifics of cardiac surgery then affect possible postoperative complications such as multiorgan failure or septic shock. The diploma thesis is divided into a theoretical and a practical part. The theoretical part describes the principle and influence of cardiopulmonary bypass on the human body and the complications that are associated with its use. Furthermore, IFN-γ is described herein as a potential marker of septic conditions that could reflect the clinical postoperative condition of patients. The practical part of the diploma thesis monitored the percentage change of selected cell populations and the production of IFN-γ in the peripheral blood of patients before and after cardiac surgery. Furthermore, the response of individual isolated populations of healthy volunteers to selected stimulators was investigated. The percentage of...
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Cellular and molecular mechanisms of immunoregulatory action of stem cells and their effect on adaptive immune cells
Boháčová, Pavla ; Holáň, Vladimír (advisor) ; Hrdý, Jiří (referee) ; Kalina, Tomáš (referee)
Regulation of immune reactions represents an entire system of maintenance of homeostasis, self-tolerance, and host defense. Regardless of intensive research, the cellular and molecular insights into immunomodulation remain incomplete. Therefore, we aimed to study different approaches to modulate the immune system, primarily focused on the induction, expansion, and activation of immunoregulatory cells. We analyzed the therapeutic effect of the combined action of mesenchymal stem/stromal cells (MSCs) and immunosuppressive drugs on the balance among T cell populations. We found that MSCs ameliorated unfavorable effects of immunosuppressants on T cell activation. As a result of this approach, T cell development was altered from the T helper (Th) 1, Th2, and Th17 cell polarization to anti-inflammatory regulatory T cell-mediated response. Additionally, we studied the effect of the immunoregulatory action of MSCs on B cells. We evaluated the impact of cytokine-primed MSCs on the induction of interleukin (IL)-10-producing B cells. Results revealed that interferon (IFN)-γ- and IL-4-primed MSCs suppressed the production of IL-10 by activated B cells. This suppression was dependent on cell-to-cell contact. In the case of IFN-γ-primed MSCs, the inhibition of IL-10 secretion involved the cyclooxygenase-2...
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Human nutrition, Bacteroides fragilis and the immune system
Veigertová, Tereza ; Hrdý, Jiří (advisor) ; Podzimek, Štěpán (referee)
The presence of bacteria in the human body is a crucial factor for immune system development and its appropriate functioning. This bachelor thesis focuses on the beneficial effects of Bacteroides fragilis and explores the possibility of altering its abundance in the colon by dietary intervention. Both Czech and foreign literature was reviewed and the practical part was carried out using a questionnaire survey. The research indicates that it is possible to affect the proportional representation of Bacteroides fragilis in the colon with specific nutrients and dietary habits. Additionally, the theoretical part describes the benefits of this bacterial species on the human immune system. Bacteroides fragilis produces short-chain fatty acids, antimicrobial substances and polysaccharide A, which are the principal components that influence the host. The practical part builds upon the findings of the theoretical part. It investigates the knowledge of a random sample of Czech citizens about the effect of diet on microbiota composition. It also explores people's view on probiotics and their acquaintance with food composition. The conclusion of the thesis is a correlation between the theoretical and practical part. The intestinal microbiota is a relatively compact unit with complex interactions. Diet can not...
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Capacity of probiotics to affect innate lymphoid cells type 3
Věcek, Jan ; Hrdý, Jiří (advisor) ; Schwarzer, Martin (referee)
Innate lymphoid cells type 3 (ILC3) are a group of relatively newly discovered lymphocytes that lack an antigen-specific receptor. Nevertheless, their important role of immune regulators on mucous membranes is evident. In addition to the development of lymphoid tissue in embryogenesis, and during ontogenesis, postnatally, ILC3 are mainly involved in maintaining intestinal homeostasis and controlling intestinal microbiota. ILC3 produces various cytokines that stimulate surrounding intestinal cells to produce antimicrobial peptides and maintain epithelial wall integrity. The major cytokine produced by ILC3 is IL-22. Th17 lymphocytes and ILC3 are similar in many respects but differ significantly in some functions. ILC3 can regulate adaptive immunity cells towards an antimicrobial response without inducing inflammation. They are also directly connected to cells of the nervous system. Some probiotic bacterial strains produce metabolites that directly affect ILC3. This mechanism could be used in new therapeutic approaches to ameliorate the severity of diseases where changes in microbiota composition and function are inducing proinflammatory responses of the host. Key words: innate lymphoid cells; IL-22; antimicrobial peptides; probiotics; microbiota
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