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Intrinsic factors in helper T-cells lineage choice
Andreyeva, Arina ; Neuwirth, Aleš (advisor) ; Chmelař, Jindřich (referee)
The process of clonal expansion of T lymphocytes, or T cells, belongs to the basic characteristics of adaptive immunity. A fundamental role in the immune response is played by the CD4+ T cells which are capable of evolving into the different subtypes (for example Th1 or Tfh) that help other types of cells to effectively eliminate pathogens. Each particular subtype activates different arms of the immune system for the most effective clearance of a particular pathogen. The way how the pathogen will be eliminated depends on the type of infection. This thesis aims to analyze relevant literature and known facts about factors that influence functional T-cell differentiation. This thesis will be mainly focused on the question of how much the T-cell receptor's structure or antigen affinity plays a role in this decision- making process. Another point of interest is the capability of T cells from one clone to produce different T helper cell subtypes, or they are preferentially biased towards a single differentiation pathway. Key words: adaptive immunity, CD4+ T cells, TCR, infections, differentiation
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Tumor Specific Signaling in T-Cell Lymphoma
Kulinich, Viktoriia ; Havránek, Ondřej (advisor) ; Kužílková, Daniela (referee)
T lymphomas are malignant tumors arising from T cells; they represent a rare variant of non-Hodgkin's lymphomas. As in other cancers, tumor T cells need to modify their signaling to support their growth and survival. T-lymphoma tumor cells are capable to adapt various signaling cascades important also in normal healthy T cells to their benefit. The aim of this work is to summarize tumor-specific signaling typical for different types of T-cell lymphomas; both, identical to the signaling of normal T lymphocytes and altered by tumor specific somatic mutations. Detailed focus is on T lymphoma most frequent and important alterations and signaling pathways. These are specifically alterations of signaling pathways associated with T-cell receptor, JAK/STAT cytokine signaling, and Notch signaling. These pathways are particularly important for the differentiation and growth of T lymphocytes in general, therefore, it is not surprising that these pathways are also often pathologically activated or deactivated in tumor cells. Keywords: lymphocytes, non-Hodgkin lymphomas, T-cell receptor, leukemia, JAK/STAT signaling, Notch signaling, oncogenic signaling pathways
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The development of swine B cells and the role of gama delta T lymphocytes in immunization of naive immune system.
Štěpánová, Kateřina
Thesis summary The process of B cell lymphogenesis in swine remains uncertain. Some reports indicate that pigs belong to a group of animal that use ileal Peyers's patches (IPP) for the generation of B cells while others point to the possibility that the bone marrow is functional throughout life. The functional subpopulations of B cells in swine are also unknown. Together with other ruminants, and also birds, γδ T cells in swine may account for >70% of all T cells which is in apparent contrast with humans and mice. The purpose of this thesis was to address these discrepancies and unresolved issues. The results disprove the existing paradigm that the IPP is primary lymphoid tissue and that B cells develop in IPP in an antigen-independent manner. On the other hand, it shows that bone marrow is fully capable of B cell lymphogenesis and remains active at least for the same period of time as it had been speculated for the IPP. This thesis also identified functionally different subsets of porcine peripheral B cells, and shows that CD21 molecules can be expressed in differential forms. Finally, this thesis identifies two lineages of γδ T cells that differ in many functional and phenotype features. This finding may explain why γδ T cells constitute of minority of lymphocytes in circulation of humans and mice.
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The development of swine B cells and the role of gama delta T lymphocytes in immunization of naive immune system.
Štěpánová, Kateřina
Thesis summary The process of B cell lymphogenesis in swine remains uncertain. Some reports indicate that pigs belong to a group of animal that use ileal Peyers's patches (IPP) for the generation of B cells while others point to the possibility that the bone marrow is functional throughout life. The functional subpopulations of B cells in swine are also unknown. Together with other ruminants, and also birds, γδ T cells in swine may account for >70% of all T cells which is in apparent contrast with humans and mice. The purpose of this thesis was to address these discrepancies and unresolved issues. The results disprove the existing paradigm that the IPP is primary lymphoid tissue and that B cells develop in IPP in an antigen-independent manner. On the other hand, it shows that bone marrow is fully capable of B cell lymphogenesis and remains active at least for the same period of time as it had been speculated for the IPP. This thesis also identified functionally different subsets of porcine peripheral B cells, and shows that CD21 molecules can be expressed in differential forms. Finally, this thesis identifies two lineages of γδ T cells that differ in many functional and phenotype features. This finding may explain why γδ T cells constitute of minority of lymphocytes in circulation of humans and mice.
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The development of swine B cells and the role of gama delta T lymphocytes in immunization of naive immune system.
Štěpánová, Kateřina ; Šinkora, Marek (advisor) ; Macela, Aleš (referee) ; Faldyna, Martin (referee)
Thesis summary The process of B cell lymphogenesis in swine remains uncertain. Some reports indicate that pigs belong to a group of animal that use ileal Peyers's patches (IPP) for the generation of B cells while others point to the possibility that the bone marrow is functional throughout life. The functional subpopulations of B cells in swine are also unknown. Together with other ruminants, and also birds, γδ T cells in swine may account for >70% of all T cells which is in apparent contrast with humans and mice. The purpose of this thesis was to address these discrepancies and unresolved issues. The results disprove the existing paradigm that the IPP is primary lymphoid tissue and that B cells develop in IPP in an antigen-independent manner. On the other hand, it shows that bone marrow is fully capable of B cell lymphogenesis and remains active at least for the same period of time as it had been speculated for the IPP. This thesis also identified functionally different subsets of porcine peripheral B cells, and shows that CD21 molecules can be expressed in differential forms. Finally, this thesis identifies two lineages of γδ T cells that differ in many functional and phenotype features. This finding may explain why γδ T cells constitute of minority of lymphocytes in circulation of humans and mice.
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Localisation of CD4 coreceptor and its variants in human T cells
Glatzová, Daniela ; Cebecauer, Marek (advisor) ; Drbal, Karel (referee)
CD4 co-receptor of main T cell receptor (TCR) is essential for proper development of T lymphocytes and their function in adaptive immune responses. It is believed that CD4 stabilizes the interaction of TCR with antigenic ligand, peptide-MHC, and thereby improves T cell-dependent responses during immune reaction. CD4 is transmembrane glycoprotein with a number of structural motifs in its intracellular domain which do not dramatically affect its sorting to the plasma membrane but can influence its local organization at nanoscale. CD4 was shown to transiently accumulate in the immunological synapse formed between T cell and antigen-presenting cell. Such accumulation is rapidly followed by its internalization and/or delocalization outside the synapse. This is in contrast with TCR which accumulates strongly in the immunological synapse and is later found enriched in the central area of this structure. It is therefore unclear how TCR and its CD4 co-receptor function together when binding to their common ligand during the initiation of signaling in T cells. We aim to study localization of CD4 at nanoscale using advanced fluorescence microscopy techniques achieving significant improvements in resolution. In this work, CD4 and its mutant variants, potentially causing its different localization at the...
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Mechanizmy regulace signální transdukce povrchovými proteiny leukocytu*.
Štěpánek, Ondřej ; Brdička, Tomáš (advisor) ; Brábek, Jan (referee) ; Vomastek, Tomáš (referee)
The core of the doctoral thesis "Regulation of signal transduction by leukocyte surface proteins" consists of three publications in international peer-reviewed journals dealing with leukocyte signaling both at the level of individual signaling pathways and in the context of a multicellular organism. Most attention is paid to signaling via the T cell receptor (TCR), which plays a central role in the development and function of T cells and represents a key signaling pathway for proper function of the adaptive component of the immune system. Transmembrane protein tyrosine phosphatase CD148 was considered a negative regulator of TCR signaling through dephosphorylation of LAT and PLCγ1 proteins. This study brings evidence that CD148 is able to modulate signaling also at the level of Lck, both positively and negatively. The net effect of CD148 activity on the TCR signaling is determined by the intracellular biochemical context, notably, the presence of another tyrosine phosphatase CD45. The second project dealt with the characterization of a transmembrane adaptor protein PRR7. This adapter inhibits TCR signaling via down-regulation of the intracellular Lck and cell surface TCR levels. The research concerning the signaling in the environment of a multicellular organism is represented by the analysis of...
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