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Matrix metalloproteinases in anterior eye segment
Paračková, Zuzana ; Ardan, Taras (advisor) ; Paňková, Daniela (referee)
Matrix metalloproteinases belong to the group of proteases which in normal tissue are responsible for degradation a and remodeling of extracellular matrix components and their activity is regulated by endogenous inhibitors. However, many patological conditions of the anterior eye segment are characterized by increased activity of matrix metalloproteinases and conversely decreased activity of their tissue inhibitors.The imbalance between matrix metalloproteinases and their inhibitors can lead to destructive proteolytic tissue damage anterior eye segment, including blindness. Key words: matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, extracellular matrix
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Immune systems dysregulation in type 1 diabetes
Paračková, Zuzana
Type 1 diabetes (T1D) is an autoimmune disease with multifactorial aetiology that involves an attack of self-reactive cytotoxic CD8 lymphocytes on insulin-producing beta cells in the pancreas. In the T1D pathophysiology, both innate and adaptive immunity mechanisms cooperate in the development of inflammation leading to autoimmune destruction. Autoreactive T lymphocytes are the canonical destructors of the beta cells, and B cells produce autoantibodies; the innate immunity cells are considered the initiators of the pathological autoimmune reaction by promoting T and B cell activation. Here, we provide evidence of both innate and adaptive immunity cell types dysregulation in patients with T1D, and that these changes occur before the onset of the disease. The changes in T regulatory lymphocytes (Tregs) and B cell subpopulations occur already in asymptomatic T1D first-degree relatives. During the first year after the onset of the disease, there is a gradual decrease in the neutrophil numbers in the periphery, which probably infiltrate the pancreas. We have focused more closely on the innate immunity dysregulation and its contribution to T1D pathogenesis. Initially, we describe that neutrophil products called neutrophil extracellular traps (NETs) are able to induce IFNγ-producing T cells through...
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Immune system dysregulation in type 1 diabetes
Paračková, Zuzana ; Šedivá, Anna (advisor) ; Filipp, Dominik (referee) ; Vlková, Marcela (referee)
Type 1 diabetes (T1D) is an autoimmune disease with multifactorial aetiology that involves an attack of self-reactive cytotoxic CD8 lymphocytes on insulin-producing beta cells in the pancreas. In the T1D pathophysiology, both innate and adaptive immunity mechanisms cooperate in the development of inflammation leading to autoimmune destruction. Autoreactive T lymphocytes are the canonical destructors of the beta cells, and B cells produce autoantibodies; the innate immunity cells are considered the initiators of the pathological autoimmune reaction by promoting T and B cell activation. Here, we provide evidence of both innate and adaptive immunity cell types dysregulation in patients with T1D, and that these changes occur before the onset of the disease. The changes in T regulatory lymphocytes (Tregs) and B cell subpopulations occur already in asymptomatic T1D first-degree relatives. During the first year after the onset of the disease, there is a gradual decrease in the neutrophil numbers in the periphery, which probably infiltrate the pancreas. We have focused more closely on the innate immunity dysregulation and its contribution to T1D pathogenesis. Initially, we describe that neutrophil products called neutrophil extracellular traps (NETs) are able to induce IFNγ-producing T cells through...
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Impacts of chemotherapy on imunoregulatory gene expression in the tumor microenvironment
Paračková, Zuzana ; Reiniš, Milan (advisor) ; Zajícová, Alena (referee)
Tumor microenvironment is an area, where the local immunosuppressive effects dominate and prevents the immune system to perform its physiological functions. The cells infiltrating the microenvironment have an important function among many cell types since they produce a large quantity of factors suppressing the immune response. In our work, we monitored the immune changes in the microenvironment during tumor growth and chemotherapy. For these purposes, we utilized the methods for analysis of the proportion and phenotype of the distinct populations of immunocytes and for analysis of the total level of expressions of selected genes associated with immunosuppression or with distinct populations of immunocytes. The aim of our work was to discover, using two types of mouse tumors (TRAMP-C2 and TC-1/A9), how 5-azacytidine (5AC), a cytostatic drug with epigenetic activity, affects the proportion of leukocytes infiltrating the tumor microenvironment and, further, whether these changes are accompanied by decreased expression of immunosuppressing genes. In addition, we have also focused on the changes of relative expression of genes encoding markers of lymphoid lines and, on other immunoregulating genes, encoding IL-6, IL-10, IL-12, IL-4 and IFNγ cytokines, in the microenvironment of these tumors....
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Matrix metalloproteinases in anterior eye segment
Paračková, Zuzana ; Ardan, Taras (advisor) ; Paňková, Daniela (referee)
Matrix metalloproteinases belong to the group of proteases which in normal tissue are responsible for degradation a and remodeling of extracellular matrix components and their activity is regulated by endogenous inhibitors. However, many patological conditions of the anterior eye segment are characterized by increased activity of matrix metalloproteinases and conversely decreased activity of their tissue inhibitors.The imbalance between matrix metalloproteinases and their inhibitors can lead to destructive proteolytic tissue damage anterior eye segment, including blindness. Key words: matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, extracellular matrix
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