National Repository of Grey Literature 286 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Mechanisms of the tolerance and homeostasis of immune cells
Tsyklauri, Oksana ; Štěpánek, Ondřej (advisor) ; Černý, Jan (referee) ; Froňková, Eva (referee)
The ability of the immune system to tolerate self-antigens while mounting appropriate responses to pathogens is indispensable for the survival of the organism. Despite years of research, many details of the mechanisms of self-tolerance are still not well understood. The objective of this thesis is to extend our knowledge of the mechanisms of immune tolerance. The core of the PhD thesis consists of five publications related to two main research directions. The first one addresses the mechanisms of peripheral immune tolerance established by regulatory T cells (Tregs). We showed that Tregs increase the quorum of self-reactive CD8+ T cells required for the induction of autoimmunity. In addition, we identified a novel subset of antigen-stimulated CD8+ T cells, which expand in the absence of Tregs. We called them super-effector T cells. We revealed that the administration of IL-2 phenocopies the absence of Tregs, i.e., it induces super- effector T cells, and enhances CD8+ T cell response in autoimmunity and cancer. Our results provide strong evidence that the major suppressive mechanism of Tregs is limiting IL-2 availability for CD8+ T cells. Furthermore, in a collaborative project, we have shown that MyD88 signaling in thymic epithelial cells contributes to the development of Tregs and thus to the...
The role of innate immunity cells in the pathogenesis of celiac disease
Dáňová, Klára ; Palová Jelínková, Lenka (advisor) ; Černý, Jan (referee)
Celiac disease is an autoimmune disease which occurs in susceptible individuals after ingestion of food containing gluten. Gluten and its monomeric fraction gliadin induce inflammatory damage of the small intestine by activating the immune cells that react strongly to gluten peptides. Gluten peptides have the ability to activate cells of adaptive as well as innate immune system. This work is focused on the production of interleukin (IL)-1 in antigen presenting cells stimulated with peptic gliadin digest. We found that monocytes and peripheral blood mononuclear cells (PBMC) isolated from blood of celiac patients secrete significantly more IL-1α and IL-1β than cells of healthy donors after stimulation with gliadin digest. The gliadin-induced IL-1β expression is controlled by a signaling cascade that includes MAPK kinase family molecules and transcription factor NF-κB. Moreover, we found that the adaptor proteins MyD88 and TRIF as well as Toll-like receptor (TLR) 2 and 4 play a role in the signaling cascade underlying gliadin-induced IL-1β expression by using murine bone marrow derived dendritic cells (BMDC). The precursor form of IL-1β in gliadin- stimulated PBMC and murine BMDC is maturated by caspase-1. In celiac PBMC the gliadin- induced maturation and secretion of IL-1β depends on the potassium...
Dual role of CD9 protein in mast cell activation
Machyna, Martin ; Dráber, Petr (advisor) ; Černý, Jan (referee)
Mast cells are well known effector cells in immune system. They have been implicated in such important processes as host defense against bacteria, toxins or parasites. However, in some cases they can develop improper reaction against harmless environmental antigens and thus causing allergies. It is therefore essential to understand signaling events that lead to activation of these cells in order to develop new treatment strategies. Newly prepared rat monoclonal antibody of IgG1 subtype raised against murine mast cells was characterized and found suitable for flow cytometry, immunoblotting and immunoprecipitation. Employing of optimized procedure for immunopurification in combination with mass spectrometry led to identification of its target cluster of differentiation (CD)9 protein. CD9 is a member of large protein family called tetraspanins. Functional studies showed that binding of this antibody to mast cells induced degranulation and early activation events such as increased tyrosine phosphorylation and enhanced levels of free cytoplasmic calcium. Interestingly, subsequent activation of these cells via antigen-mediated aggregation of the high-affinity IgE receptor (FcεRI) led to decreased degranulation, calcium response and tyrosine phosphorylation of several substrates. Importantly, anti-CD9 antibody did...
Cell-mediated peripheral tolerance in lymph nodes
Brabec, Tomáš ; Filipp, Dominik (advisor) ; Černý, Jan (referee)
Tolerance of immune system to body-self constituents is a crucial issue for immunologists to solve. While the mechanisms of central tolerance are now described to well extent, antigen-specific tolerance mechanisms on immunological periphery are just beginning to be revealed, characterized and appreciated. Recently, novel models of peripheral tolerance emerged. Particularly, a model based mostly on lymph node stromal cells could be of profound importance, since it provides answers to some fundamental questions in tolerance immunology. So far, no review paper highlighting these newly discovered roles of lymph node stromal cells was published. Therefore, in this study we summarize data covering this topic, published up-to-date. Further, this text provides a basic overview of lymph node functional anatomy. To better illustrate the topic, we also show some experimental evidence demonstrating lymph node architecture and the localization of extrathymic Aire-expressing cells, one of the lymph node-resident populations, recently implicated in peripheral tolerance maintenance. Powered by TCPDF (
Biochemická a funkční charakterizace nového transmembránového adaptorového proteinu NVL
Vonková, Ivana ; Brdička, Tomáš (advisor) ; Černý, Jan (referee)
In T cells, signalling events initiated at the immunological synapse by T cell receptor (TCR) have been already thoroughly studied. In contrast, signalling pathways involved in MHCII-mediated signal transduction on the APC side of this structure are still rather poorly understood. Transmembrane adaptor proteins (TRAPs) are a class of proteins with an essential role in signalling triggered by TCR and other immunoreceptors. So far no TRAPs involved in MHCII signalling have been identified. In this work a new TRAP, highly enriched in the immunological synapse in APCs is described and termed Nvl. Nvl is expressed exclusively in professional antigen presenting cells - B cells, monocytes/macrophages and dendritic cells, and the level of its expression positively correlates with the expression of MHCII. Nvl is present in tetraspanin microdomains and together with tetraspanins it is localized to the polarized structures of the cell, including uropod, cleavage furrow, and, most interestingly, the immunological synapse. The presence in the immunological synapse indicates possible role for Nvl in MHCII- mediated signal transduction. Indeed, Nvl becomes tyrosine-phosphorylated after stimulation via MHCII, although strong phosphorylation has also been observed after FcγR stimulation or treatment with...
Mechanisms of MHCII signaling in B lymphocytes
Kotlabová, Klára ; Brdička, Tomáš (advisor) ; Černý, Jan (referee)
During the initiation of an antigen-specific immune response, peptide fragments originating from the antigen are presented in complex with MHC class II glycoproteins (MHCgpII) on the surface of the antigen presenting cells (APC). Antigen recognition by T lymphocyte is accompanied by the formation of the molecular structure at the interface with APC called immunological synapse (IS). During this contact, signal transduction is initiated at both, T lymphocyte and APC, sides of the IS. For a long time it was thought that the only function of MHCgpII is presentation of antigen. However, later it was found that stimulation of MHCgpII led to triggering of signals contributing to decision about the further fate of APC. MHCgpII do not have any signaling motifs in their cytoplasmatic domains, and so associated molecules are necessary for the transduction of the signals. This work focuses on B lymphocytes in which the associated molecules are Ig alfa/beta, MPYS, CD19 and CD20. After the stimulation of MHCgpII these proteins mediate signaling events including activation of several families of protein kinases, phospholipase C, mobilization of calcium and activation of transcriptional factors NFAT and AP-1. In B lymphocytes, activities of these pathways may result in proliferation and differentiation but also in the...
Studying immune system using MHC II/ EGFP knock-in mouse
Zadražil, Zdeněk ; Černý, Jan (advisor) ; Tlaskalová - Hogenová, Helena (referee)
The immune system is essential for keeping the integrity of multicellular organisms. We were able to make a step forward in studying the complex immune reactions in mammals in vivo and/ or in situ using the major histocompatibility complex (MHC) class II/ enhanced green fluorescent protein (EGFP) knock-in mouse model. Due to the EGFP visualization of MHC II expressing cells we were able to observe antigen presenting cells, which are essential for the onset of immune responses, in their natural environment. Thus, we report some original features of the immune system. We have identified MHC II+ cell clusters with unknown, probably unique function, in the intestine. We have also described MHC II+ cell migration to the lactating mammary gland and tested few hypotheses about the role of this phenomenon for the development of the mammary gland, milk secretion or infant immune system establishment. Lastly, we observed residential macrophages in the cornea. The presence of APCs in the cornea is a very contradictory issue due to the fact that cornea is an immunologically privileged tissue and therefore harbors special immune features. key words: antigen presenting cells (APC), major histocompatibility complex class II (MHC II), enhanced green fluorescent protein (EGFP), immune system, knock-in mouse model

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See also: similar author names
60 ČERNÝ, Jan
4 ČERNÝ, Jaroslav
32 ČERNÝ, Jiří
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