|
|
The role of neutrophils in preeclampsia
Miková, Eliška ; Hrdý, Jiří (advisor) ; Grobárová, Valéria (referee)
Preeclampsia is currently one of the leading causes of maternal morbidity and mortality. Disease development is caused by multiple factors but the main trigger remains unknown. Preeclamptic placentas are defined by increased inflammatory environment. One of the first cells to enter the site of inflammation are neutrophils. Current studies uncover considerable heterogeneity of neutrophils which used to be considered as terminally differentiated population with a very limited plasticity. Disbalance in the proportional and functional properties of proinflammatory and immunosuppressive neutrophil subpopulations including myeloid derived suppressor cells can lead to severe pregnancy complications such as preeclampsia. Better understanding of the origin of abnormal neutrophil subpopulations and their role in the pathogenesis of preeclampsia could help reveal possible targets for therapeutic intervention. Key words: neutrophil subpopulations, preeclampsia, NETosis, myeloid derived suppressor cells, myeloperoxidase, elastase, PD-L1, inflammation
|
|
|
Difference in T regulatory cells in cord blood of children of healthy and allergic mothers
Macholdová, Kateřina ; Hrdý, Jiří (advisor) ; Grobárová, Valéria (referee)
Allergic diseases belong to one of the most common diseases and their incidence is increasing worldwide, especially among children and adolescents. The development of an allergic disorder occurs already in the early postnatal period and several factors have been described that can predispose the newborn to an allergic disease. However, the mechanism of allergy development has not yet been fully elucidated. The important immune cells involved in this mechanism are regulatory T cells (Treg). Their function is the formation of central tolerance to autoantigens and peripheral tolerance towards harmless antigens present in the external environment, including allergens. The aim of this work is to compare the proportion and functional properties of Treg in children of healthy mothers (children with low risk of allergic disease development) and children of allergic mothers (children at high risk of allergic disease development). Both the total Treg population and individual subpopulations (natural (n) Treg and induced (i)Treg) in the whole umbilical cord blood of both groups of children were monitored. To assess the functional properties, Treg were isolated from cord blood by magnetic separation and subsequently co-cultured with CD4+CD25-T cells or cord blood mononuclear cells (CBMC) stained with...
|
|
|
Dietary factors in the development of type 1 diabetes
Fiala, Marek ; Funda, David (advisor) ; Grobárová, Valéria (referee)
Type 1 diabetes mellitus is an autoimmune disease which develops in genetically susceptible individuals and whose incidence rapidly increases, especially in developed countries. Type 1 diabetes is believed to be strongly associated with the environment: viruses, stressful life events or the absence of exposition to antigens in early life increase its incidence. Antigens to which we are expressed continuously are food antigens. Gluten, milk proteins or the intake of vitamin D precursors clearly influence type 1 diabetes pathogenic process. This bachelor's thesis aims to describe our current knowledge on the role of dietary factors in type 1 diabetes, their possible immune mechanisms and also interplay with other environmental factors. Key words: type 1 diabetes, dietary factors, gluten-free diet, immune mechanisms, prevention, NOD mouse, mucosal immunity
|
|
|
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,...
|
|
|
Regulatory CD8+ T lymphocytes
Chadimová, Tereza ; Štěpánek, Ondřej (advisor) ; Grobárová, Valéria (referee)
Regulatory T cells are essential for the maintenance of peripheral immune tolerance, preventing alloimmunity and pathogen-induced immunopathology. While regulatory CD4+ T lymphocytes have been studied for over two decades, the existence of regulatory T lymphocytes in the CD8+ compartment is still controversial. Through the years, multiple CD8+ T lymphocytes subpopulations have been reported to exhibit regulatory activity, yet none has been canonically recognized. The aim of this thesis is to review current knowledge of these putative CD8+ regulatory lymphocytes and evaluate whether or not these subsets can be established as regulatory T cells. The emphasis of this thesis will be put on the phenotypic characteristics, regulatory activity and inhibitory mechanisms of these cells. Keywords: CD8+ Regulatory T lymphocytes, immunological self-tolerance, immunosuppression
|
|
|
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. Identification of prognostic markers pointing to increased risk of allergy development, allows introduction of early preventive measures. Probiotic supplementation could be one the preventive measure. 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 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 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) was measured by flow cytometry. The presence of cytokines and transcription factors characteristic for particular...
|
|
|
Cytokine/anti-cytokine mAb complexes and their biological activity
Hnízdilová, Tereza ; Kovář, Marek (advisor) ; Grobárová, Valéria (referee)
biologická aktivita některých cytokinů může být paradoxně zvýšena tvorbou komplexu některými svými monoklonálními protilátkami (mAb) rozpoznávajícími tento cytokin. Prodloužení poločasu eliminace z 2 mAb komplexy, neboť v použitém klonu mAb dochází k selektivní stimulaci buď CD25 2/S4B6 komplex) buněk. Díky výrazné stimulaci NK buněk a paměťových CD8 lymfocytů a pouze mírné stimulaci Treg buněk by IL nahradit konvenční IL vysoce selektivní stimulací Treg buněk naopak mohly uplatnit při léčbě autoimunitních onemocnění a transplantacích. Potenciálně klinicky využitelné jsou dále IL stimulaci žírných buněk, IL plazmatickými buňkami či IL proliferaci a přežívání T lymfocytů. Imunokomplexy mohou být tvořeny také cytokinem a jeho 15Rα komplexy představují generaci IL onistů, které mohou být díky stimulaci expanze NK buněk a paměťových CD8 T lymfocytů využity jako Klíčová slova 15Rα komplexy
|
|
|
Therapeutic Nanoparticles and Immunotoxicity
Lehutová, Daniela ; Vannucci, Luca Ernesto (advisor) ; Grobárová, Valéria (referee)
Nanočastice sú submikroskopické štruktúry vyhotovené z rôznych materiálov s obrovským terapeutickým potenciálom. Rovnako predstavujú nový nástroj pre lepšie cielenie a podávanie liečiv do jednotlivých tkanív. Bolo vynaložených mnoho pokusov pre vyvinutie terapeutík, ktoré budú lepšie kompatibilné v organizme a zároveň by zlepšili účinnosť moderných liekov. Na rozdiel od bežne používaných spôsobov pre podávanie liečiv, enkapsulovaná forma predstavuje obrovskú výhodu pri znižovaní vedľajších účinkov oproti bežne používaných liekoch. V tejto práci sú porovnávané výhody použitia nanočastíc spolu s ich možným rizikom, najmä na ich munitný systém. Vzhľadom k tomu, že toxicita sa líši v závislosti na chemicko fyzikálnych vlastnostiach a tkanivách, v ktorých sa akumulovali, musí byť zvolená vhodná stratégia, aby sa predišlo možných nežiaducim účinkom. Z tohto dôvodu je potrebné zvážiť preventívne opatrenia a správne upraviť dané nanočástice predtým, než budú použité v organizme, rovnako ako spôsobená odpoveď organizmu a jej dôsledok musia byť vhodne monitorované. Zvýšená pozornosť musí byť venovaná príprave nanočastíc, aby sa predišlo prípadnej kontaminácii a nebezpečenstvu pre laboratórny personál. Kľúčové slová nanočástice, podávanie liečiv, imunita, toxicita, teranostika
|
|
|
The role of bacterium Escherichia coli in the tumorigenesis of colorectal carcinoma
Čurnová, Lenka ; Klimešová, Klára (advisor) ; Grobárová, Valéria (referee)
Colorectal carcinoma is a severe disease of colon. It belongs to the cancers with the highest incidence and also high mortality. In the process of tumorigenesis, there are applied various mechanisms, mainly DNA damage and subsequent reparation and inflammation. Gut microbiota plays an important role in development of the colorectal cancer influencing cancer microenvironment. Microbiota triggers inflammatory response or produces different toxins. The diploma thesis was aimed on the relation between the presence of cyclomodulin genes in the genome of individual strains of bacterium Escherichia coli and their genotoxic features. To follow direct influence of epithelial cells by microbiota, we used in vitro model. We chose E. coli as a model microorganism because it is common bacterium of human gut, moreover, as facultative anaerob it is easily cultivated. We used six strains of E. coli with different relation to the host organism including probiotic, comensal and pathobiont. In probiotic strains of E. coli (Nissle 1917 and O83), we detected less genes for cyclomodulins than in other strains. We did not observed significant differences in genotoxic features of the strains. Also, we did not detect any changes in viability, proliferation, activation of repair mechanisms or p53 fosforylation caused by...
|
|
|
Mechanisms of immunosuppressive drug-mediated effect on mesenchymal stem cell properties
Vacková, Julie ; Krulová, Magdaléna (advisor) ; Grobárová, Valéria (referee)
Mesenchymal stem cells (MSC) defined as multipotent, nonhematopoietic stem cells have been shown to possess various immunosuppressive properties. Thus they can be used to attenuate transplant rejection and also for treatment of autoimmune diseases. But simultaneously with MSC patients take immunosuppressive drugs and there is no evidence how this medication affect MSC. The goal of this study is to elucidate how frequently used immunosuppressive drugs cyclosporineA, mycophenolate mofetil, rapamycin, dexamethasone and prednisone influence immune-related parameters of mice and human MSC. Here we show that MSC from various sources are affected differentialy after short-term exposure of the tested immunosuppressants. Only cyclosporine A does not change immune-related parameters of mice MSC in the comparison to other immunosuppressants. However, cyclosporine A, mycophenolate mofetil and rapamycin enhance human MSC expression of TSG-6, PD-L1 and TGF-β which are involved in inhibition of lymphocyte proliferation and effector function, inhibition of dendritic cell maturation and in support of tolerogenic phenotype of macrophages. Although glucocorticoid drugs promote survival of human MSC and expression of Fas-L they reduce expression of molecules that mediate immunosuppression. In this respect, the best...
|
guest ::
