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The effect of intranasal immunization by delipidated Bacillus firmus on immune response in NALT
Hnilicová, Šárka ; Hrdý, Jiří (advisor) ; Hájková, Michaela (referee)
Influenza is a serious illness worldwide, causing high morbidity and mortality. 10-20% of world population fall ill with influenza each year and 250 000 - 500 000 people die annually. The most efficacious protection to date is vaccination. Current vaccines are efficient only one season because of fast mutation rate of influenza virus. The effort to create an effective vaccine faces lack of potent adjuvant, which can adequately stimulate and modulate immune system to protect organism from virus infection. Moreover, todays vaccines administered parenterally do not induce immune response on mucosal surfaces. Bacillus firmus, a Gram-positive non-pathogenic bacterium, has strong immmune-modulating properties and is able to induce cross-protection when administered with influenza virus antigens. Immunization with Bacillus firmus stimulates production of neutralizing antibodies, but other mechanisms of its action remain to be elucidated. To better understand the mechanisms how is antiviral immunity enhanced by Bacillus firmus (delipidated fraction, DBF), the effect of immunization with DBF only was studied on mouse model. In last decade it has become obvious that intranasal immunization can induce both systemic and mucosal immune response and in case of influenza it can induce cross-protection. Therefore...
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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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Immune response of different subpopulations of dendritic cells to probiotic strain of E. coli O83:K24:H31
Gorelová, Miroslava ; Hrdý, Jiří (advisor) ; Černý, Jan (referee)
Allergy as one of the most frequent pathologies worldwide belongs to illnesses with constantly increasing incidence even amongst young children. It develops in genetically predisposed individuals whose dendritic cells (DC) are, after contact with allergen, able to polarize the immune response predominantly to Th2, while Th1 response is supressed. One of the possible preventive measures to avoid an allergic disease developement could be an early postnatal supplementation of chosen probiotic bacterial strains or their mixtures. One of them is a well characterized strain Escherichia coli O83:K24:H31 (E. coli O83). Administering of this probiotic vaccine called Colifant Newborn is showing to be an effective prophylaxis to decrese the incidence of allergies in children with predisposition to their developement. The aim of my diploma thesis was to experimentally confirm the capacity of E. coli O83 to support maturation of two main subpopulations of newborn DC available from cord blood: myeloid dentritic cells - mDC and plasmacytoid dentritic cells - pDC. This DC subpopulations were isolated from cord blood of children born to healthy (non-allergic) mothers who had a low risk of allergy development or from children of allergic mothers who had an increased risk of allergy development. Subsequently, after...
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Immune response of different subpopulations of dendritic cells to probiotic strain of E. coli O83:K24:H31
Gorelová, Miroslava ; Hrdý, Jiří (advisor) ; Grobárová, Valéria (referee)
Allergy, as one of the worldwide most frequent pathologies, belongs to illnesses with constantly growing incidence among young children. In genetically predisposed individuals, dendritic cells are able to polarize the immune response of Th2 in contact with the allergen. Postnatal probiotic supplementation could be one the preventive measure to prevent the development of allergic diseases. It has been shown that introduction of selected probiotic strains or mixtures can prevent development of allergy. In this diploma thesis, the capacity of probiotic strain Escherichia coli O83:K24:H31 (E. coli O83) to support maturation of dendritic cells (DC) and polarization of immune responses was tested. Introduction of this probiotic vaccine called Colinfant Newborn appears to be suitable preventive measure, lowering allergy incidence in children with predisposition to development of allergy. The aim of this diploma thesis was to observe capacity of E. coli O83 to support maturation of the two main subpopulations of dendritic cells (myeloid dendritic cells - mDC and plasmacytoid dendritic cells - pDC) in cord blood of newborns of healthy mothers (children with relatively low risk for allergy development) and allergic mothers (children with relatively high risk for allergy development). To achieve this goal,...
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The role of innate lymphoid cells in influenza virus infection
Mouyabi, Flaviancia ; Hrdý, Jiří (advisor) ; Kössl, Jan (referee)
Innate lymphoid cells (ILCs) are recently discovered group of innate immune cells. They do not have antigen-specific receptors but they can be activated by cytokines similarly to T lymphocytes. ILCs have a crucial role in the regulation of inflammation, tissue repair, containment of commensals, anti-infection immunity and regulation of tissue homeostasis. The presence of mouse and human ILCs can be detected in the lung during and after influenza virus infection when ILCs contribute to the restoration of damaged lung parenchyma. ILCs directly or indirectly provide protection against viral infections by secretion of various cytokines and co-operation with other cells (e.g. T cells, macrophages). Overall, lung ILCs are important in immune responses and tissue homeostasis, but further studies on this topic are needed to fully understand their role. The aim of this thesis was to specifically characterize these cells, focus on their function in the lung, and describe their role in the course of influenza virus infection.
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Immunologic characteristics of milk: Differences between nonallergic mothers
Hrdý, Jiří
Immunologic Characteristics of Milk: Differences Between Nonallergic and Allergic Mothers Maternal milk influences positively the development of newborn's immune system. Differences between milk of healthy and allergic mothers are not well established and the results concerning effect of allergic milk on newborn's immunity are controversial. In the present work, the effects of healthy and allergic colostrum/milk on the stimulation of cord blood lymphocytes of children of healthy and allergic mothers were studied. The properties of milk and cord blood cells were tested using cytokine and immunoglobulin detection by immunoenyzmatic methods (ELISA and ELISPOT respectively), cell cultivation, 3 H-thymidine incorporation and cytokine mRNA expression by real-time PCR. According to the results obtained, there are not larger differences between healthy and allergic milk. Colostrum/milk in high concentration suppresses proliferation of cord blood lymphocytes after stimulation by polyclonal activators. Lymphocytes of children of allergic mothers incorporate 3 H-thymidine more intensively than lymphocytes of children of healthy mothers. On the other hand, colostrum/milk increases Ig production by stimulated cord lymphocytes in vitro. Cocultivation of milk cells with stimulated cord mononuclear leucocytes in Transwell...
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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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Particular subpopulations of T regulatory cells and its role in allergic diseases
Kubrová, Romana ; Hrdý, Jiří (advisor) ; Holáň, Vladimír (referee)
CD4+ regulatory T cells represent a heterogeneous population of T lymphocytes which can be divided into a wide range of individual subpopulations by means of characteristic molecular markers and sites of origin. Regulatory T cells play a role in the majority of immune responses. One of their key functions is the provision of tolerance to potentially harmless environmental and food antigens. In individuals whose mechanism of tolerance failed and allergic disease has developed, impaired function and reduced proportion of regulatory T cells were demonstrated. Increasing prevalence of allergic diseases across the world population leads to the search for prognostic markers that point to an increased risk of allergic diseases development and whose early diagnosis would allow introduction of appropriate preventive measures. While such a prognostic marker appears to be a subpopulation of naturally occuring regulatory T cells, the subpopulation of induced regulatory T cells plays an irreplaceable role in specific allergen immunotherapy. Key words Regulatory T cells, allergic diseases, cord blood, FoxP3, specific allergen immunotherapy
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Different capacity of in vitro generated monocyte-derived dendritic cells of newborns of healthy and allergic mothers to prime immune responses
Súkeníková, Lenka ; Hrdý, Jiří (advisor) ; Javorková, Eliška (referee)
(EN) Reduced microbial stimulation of an immature neonatal immune system can lead to a poor balance adjustment of immune responses, thus contributing to the development of allergic diseases, whose incidence continues to rise. One of the promising precautionary measures seems to be an early preventive administration of probiotic bacteria to pregnant or nursing mothers, or to newborns. Previous works have described a beneficial effect of Escherichia coli O83:K24:H31 (E. coli O83) in the prevention of allergic diseases. In order to contribute to the clarification of E. coli O83 effects on the neonatal immune system, its immune- modulating properties were tested in vitro on umbilical cord blood cells. The ability of E. coli O83 to support the maturation of in vitro-derived dendritic cells from cord blood precursors (moDCs) of the children of healthy (children with a relatively low risk of allergy) and allergic (children at a relatively high risk of developing allergies) mothers was tracked by flow cytometry, qPCR and ELISA. Probiotic bacteria-stimulated moDCs were subsequently cultured with autologous naive CD4+ T lymphocytes and immune response polarization was also characterised by flow cytometry, qPCR, and ELISA. It was evident from the results that E. coli O83 promoted moDCs maturation. The presence of...
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