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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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Immunotherapy of ovarian carcinoma with dendritic cells
Partlová, Simona ; Rožková, Daniela (advisor) ; Froňková, Eva (referee)
V ANGLICKÉM JAZYCE Immunotherapy of ovarian carcinoma with dendritic cells Anticancer immunotherapy is a therapeutical strategy aimed at elicitation and maintenance of immune responses against cancer cells. In this study we have focused on immunotherapy of ovarian cancer, because it is one of the most common gynaecological tumors with poor prognosis and high mortality. Our immunotherapy protocol involves preparing dendritic cells (DC) from monocytes isolated from patient's peripheral blood, which are subsequently pulsed with irradiated cells of established ovarian cancer cell line. These immature pulsed DC are maturated and subsequently co-cultivated with autologous T lymphocytes. The aim of this study was to demonstrate, that DC are able to elicit specific immune response after addition of suitable mature agens in combination with apoptotic ovarian tumor cells. Our observations indicate that 24 hours are sufficient for induction of tumor cells apoptosis. Additionally, we have shown that DC successfully ingested most of the apoptotic tumor cells after 4 hours of co-incubation. Furthermore, we have found out that ingestion of apoptotic cells by dendritic cells, which are stimulated with polyI:C, inhibits maturation of DC and consequently also production of cytokines IL-12p70, IL-6 and TNF-α. Whereas...
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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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Immunomodulation of dendritic cells by adenylate cyclase toxin from B. pertussis
Jáňová, Hana ; Brdička, Tomáš (referee) ; Adkins, Irena (advisor)
Adenylate cyclase toxin (CyaA) produced by the causative agent of whooping cough Bordetella pertussis, is a key virulence factor important for colonization of the host. CyaA targets preferentially myeloid phagocytes expressing CD11b/CD18 integrin. By elevating cytosolic cAMP in the host cells, CyaA interferes with their phagocytic, chemotactic and oxidative burst capacities. Furthermore, CyaA modulates the secretion of cytokines and the maturation state in LPS-stimulated dendritic cells (DC) by affecting the expression of costimulatory molecules. In this study, we investigated the effects of CyaA on the capacity of murine bone-marrow DC to prime CD4+ and CD8+ T cells in response to ovalbumin epitopes delivered by the CyaA-AC- toxoid, as a model antigen. Further, we examined the possible impact of CyaA on the antigen uptake and processing for MHC class I and II-restricted presentation by DC, as we previously observed a decreased T cell stimulatory capacity of CyaA-treated DC in response to soluble ovalbumin. We found out that the high levels of cAMP generated by CyaA in LPS-stimulated DC account for the decreased presentation of ovalbumin epitopes carried by CyaA-AC- toxoid on MHC class I and II molecules, thereby impairing the CD8+ and CD4+ T cell responses. Whereas CyaA did not influence the...
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The effect of extreme physical exertion on the percentage of dendritic cell subpopulations in professional athletes as correlated with change in adrenaline levels
Fischerová, Barbara ; Kolář, Pavel (advisor) ; Radvanský, Jiří (referee)
The main goal of this tesis is to describe changes in representation of various subpopulations dendritic cells (myelogenic and plasmocytoigenic) in peripheral blood after intense physical stress and to review their activation status. Early count changes and changes of function of basic elements of cellular immunity after a sport load was described, whereas a behaviour of circulating dendritic cells hasn't been studied yet. The amount and the stage of differentation of dendritic cells was specified by analysis of blood samples taken before and after the load. According to the result of the tesis the reaction to extreme physical load had two effects. The amount of dendritic cells was increased, whilst the expression of kostimulative molecules (their activation) was decreased. Described changes support an opinion, that physical load initates reaction to a danger of body damage. Powered by TCPDF (www.tcpdf.org)
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The effect of tick´s serpin IRS-2 on dendritic cells activated by TLR4 ligand
POSPÍŠILOVÁ, Šárka
IRS-2 is the inhibitor of serine proteases from the Ixodes ricinus tick. My task in this thesis was to find out the effect of the IRS-2 on dendritic cells activated by TLR4 ligand or by Borrelia afzelii. This effect was studied on several levels. I focused on the cytokine production, the expression of costimulatory molecules and cell signaling pathways. The results show that the IRS-2 may inhibit the expression of costimulatory molecules CD-80 a CD-86 on the cell surface, but this finding needs to be confirmed again. The production of cytokines was not affected by the IRS-2. The effect of the IRS-2 on the activity of p38, Erk1/2 nor NF-?B in LPS stimulated cells vas not observed. The fosforylation of STAT 3 in cells activated by the B. afzelii was lowered by the IRS-2.
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Účast monocytů a dendritických buněk v patogenezi celiakie
Tučková, Ludmila ; Palová-Jelínková, Lenka ; Rožková, D. ; Černá, M. ; Pecharová, Barbara ; Smythies, L. ; Smith, P. ; Dvořák, M. ; Fruhauf, P. ; Tlaskalová, Helena
This work studies the involvement of monocytes and dendritic cells in coelias cisease pathogenesis
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Gliadin fragments induce phenotypic and functional maturation of human dendritic cells
Palová-Jelínková, Lenka ; Rožková, D. ; Pecharová, Barbara ; Bártová, J. ; Šedivá, A. ; Tlaskalová, Helena ; Spíšek, R. ; Tučková, Ludmila
Gliadin treatment also resulted in increased NF- B/DNA binding activity of p50 and p65 subunits. Taken together, gliadin peptides can contribute to overcoming the stage of unresponsiveness of immature DC by inducing phenotypic and functional DC maturation, resulting in more efficient processing and presentation of gliadin peptides to specific T lymphocytes
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