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Cytokine networks and their impact on the immune profile of acute myeloid leukemia (AML) patients
Ptáček, Antonín ; Musil, Jan (advisor) ; Fišer, Karel (referee)
Acute myeloid leukemia (AML) is a malignant hematological disorder characterized by aberrant expansion of blasts in the bone marrow and peripheral blood. The immune system protects the body from leukemia by eliminating transformed cells. However, in AML, the abilities of immune cells are affected both by direct contact between leukemic cells and effector cells, as well as by cytokines, metabolites and other soluble proteins that, together with the cells, form the specific AML microenvironment. The effects of cytokines and other soluble molecules in the AML microenvironment are not sufficiently described yet. This thesis aimed to optimize and implement a multiparametric flow cytometry panel for the measurement of cell populations and to implement multiparametric assays for the analysis of cytokine levels, chemokines and other soluble proteins in plasma. The following goal was to use these methods to characterize the frequency and functional phenotype of cell populations and the levels of the soluble proteins and to describe their influence on disease severity and overall survival of the patients. We also tried to find novel biomarkers of the immune escape of leukemic cells. In patients, we observed a suppressive microenvironment with aberrant levels of soluble receptors and other proteins. This...
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The role of γc cytokines in the immune system and cancer immunotherapy
Ptáček, Bohumil ; Kovář, Marek (advisor) ; Adkins, Irena (referee)
Cytokines are proteins produced mostly by cells of hematopoietic origin and transduce signals via engaging cell surface receptors on either the cytokine-producing cells (autocrine signaling) or other target cells (paracrine signaling). Common cytokine receptor subunit (γc) cytokines are small glycoproteins belonging to type I cytokines with pleiotropic activities in both the innate and adaptive immune systems. All γc cytokines share a γc receptor subunit in their complete receptors. The first part of this thesis aims to summarize information about the biology of γc cytokines, their receptors, and their role in the immune system and its functions. The second part discusses the use of γc cytokines in cancer immunotherapy, presenting examples of particular γc cytokine therapies, and describes the approaches to improve the pharmacological features of γc cytokines or efficiently combine them with other immunotherapies and anticancer treatments. Keywords: γc cytokine, cytokine receptor, T cell, NK cell, cancer immunotherapy
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B- and T- lymphocyte subpopulations in lymphocyte-associated immunodeficiencies
Šinkorová, Vendula ; Kalina, Tomáš (advisor) ; Javorková, Eliška (referee)
The antigen-specific immunity consists of cells called T and B lymphocytes. These cells together with cells of non-specific (innate) immunity begin their development in fetal liver and later in bone marrow from the common progenitor, the hematopoietic stem cell. Both B and T lymphocyte lineages then undergo differentiation which is regulated by many cytokines and transcriptional factors and leads to very heterogeneous cohort of subsets. Because the immune system is not only protecting the organism from infections and malignant growth but also from itself, lymphocyte differentiation must pass many checkpoints where B and T clones are strictly selected. Cells of both lineages closely communicate with each other and also with cells of innate immunity. If, due to mutation of protein encoding genes, disturbance of differentiation or malfunction of effector activities providing some of these functions occurs, an immune system malfunction called immunodeficiency arises. Multiparametric immunophenotyping followed by flow cytometry examination has been proven one of the most suitable techniques for studying lymphocyte subsets and lymphocyte- associated immunodeficiencies. Here we describe examples of primary lymphocyte- associated immunodeficiencies, how they affect individual lymphocyte subsets, what it...
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Eight color flow cytometry test development for primary imunodeficiency patients
Šinkorová, Vendula ; Kalina, Tomáš (advisor) ; Brdička, Tomáš (referee)
Primary immunodeficiencies represent a heterogeneous group of hereditary immune system malfunctions with very variable causes and symptoms. Multiparametric flow cytometry has become an important tool in primary immunodeficiency diagnostics and research because it provides detailed information on the phenotype of individual immune cells and their proportions in circulation. We have developed a complex monoclonal antibody panel composed of five eight-color tubes which is designed for immunophenotyping of basic lymphocyte subsets and further analysis of B and T cell subpopulations. We have optimized and standardized the panels so they will identify any changes originating from primary immunodeficiencies and provide comparable data on the level of cooperation between more laboratories. This was achieved by cooperation of six European research facilities which are all parts of the Euroflow consortium. The panels have been validated both on peripheral blood samples from healthy donors and patients with either gentically defined primary immunodeficiency or common variable immunodeficiency. Keywords: T lymphocyte, B lymphocyte, primary immunodeficiency, flow cytometry, immunophenotyping, Euroflow, optimization, standardization
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B- and T- lymphocyte subpopulations in lymphocyte-associated immunodeficiencies
Šinkorová, Vendula ; Kalina, Tomáš (advisor) ; Javorková, Eliška (referee)
The antigen-specific immunity consists of cells called T and B lymphocytes. These cells together with cells of non-specific (innate) immunity begin their development in fetal liver and later in bone marrow from the common progenitor, the hematopoietic stem cell. Both B and T lymphocyte lineages then undergo differentiation which is regulated by many cytokines and transcriptional factors and leads to very heterogeneous cohort of subsets. Because the immune system is not only protecting the organism from infections and malignant growth but also from itself, lymphocyte differentiation must pass many checkpoints where B and T clones are strictly selected. Cells of both lineages closely communicate with each other and also with cells of innate immunity. If, due to mutation of protein encoding genes, disturbance of differentiation or malfunction of effector activities providing some of these functions occurs, an immune system malfunction called immunodeficiency arises. Multiparametric immunophenotyping followed by flow cytometry examination has been proven one of the most suitable techniques for studying lymphocyte subsets and lymphocyte- associated immunodeficiencies. Here we describe examples of primary lymphocyte- associated immunodeficiencies, how they affect individual lymphocyte subsets, what it...
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