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Mechanisms of immune response against kidney allograft
Švachová, Veronika
Kidney transplantation improves the prognosis and quality of life of patients with end- stage renal disease. However, the occurrence of rejection still represents a major complication that can lead to failure of allograft function. In our work, we have studied the phenotypic changes of subpopulations of B lymphocytes and monocytes, which represent one of the key players involved in immune responses against kidney transplantation. In the part of the research devoted to B lymphocytes, we have observed a different redistribution of individual B cell compartments in the peripheral blood during the first year after transplantation without significant differences between used immunosuppression. We have demonstrated that sensitized and rejected patients had a lower level of IgMhigh CD38high CD24high transient B cells. These results support the hypothesis of a protective role of transient B lymphocytes. Activation of monocyte subpopulations in peripheral blood in the posttransplantation perion was also subject of research. We have compared a cohort of patients with normal graft function with a group of patients with acute rejection. The level of "transient" monocytes and HLA-DR expression in a subset of "non-classical" monocytes did not decrease in patients with rejection, compared to the group with a...
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Mechanisms of immune response against kidney allograft
Švachová, Veronika ; Stříž, Ilja (advisor) ; Mrázek, František (referee) ; Posová, Helena (referee)
Kidney transplantation improves the prognosis and quality of life of patients with end- stage renal disease. However, the occurrence of rejection still represents a major complication that can lead to failure of allograft function. In our work, we have studied the phenotypic changes of subpopulations of B lymphocytes and monocytes, which represent one of the key players involved in immune responses against kidney transplantation. In the part of the research devoted to B lymphocytes, we have observed a different redistribution of individual B cell compartments in the peripheral blood during the first year after transplantation without significant differences between used immunosuppression. We have demonstrated that sensitized and rejected patients had a lower level of IgMhigh CD38high CD24high transient B cells. These results support the hypothesis of a protective role of transient B lymphocytes. Activation of monocyte subpopulations in peripheral blood in the posttransplantation perion was also subject of research. We have compared a cohort of patients with normal graft function with a group of patients with acute rejection. The level of "transient" monocytes and HLA-DR expression in a subset of "non-classical" monocytes did not decrease in patients with rejection, compared to the group with a...
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Complex Evaluation of Immune Defects in Patients with Chronic Lymphocytic Leukemia
Vodárek, Pavel ; Belada, David (advisor) ; Doubek, Michael (referee) ; Papajík, Tomáš (referee)
Complex evaluation of immune defects in patients with chronic lymphocytic leukemia MUDr. Pavel Vodárek Abstract of dissertation thesis Chronic lymphocytic leukemia (CLL) is associated with significant combined immunodeficiency. Amongst most important immune defects are hypogammaglobulinemia and changes in relative and absolute counts of different lymphocyte populations and subsets. As consequence of these changes, there can be higher frequency of infections and progression of CLL itself. The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) levels and lymphocyte populations has not been extensively studied. In this dissertation thesis, we analysed Ig levels and lymphocyte populations (using flow cytometry) in 45 patients with indolent untreated CLL and 90 patients with progressive disease indicated for treatment. In 58 patients, we evaluated the impact of first-line CIT. For lymphocyte populations' analysis, we had also cohort of 34 healthy controls. Patients with progressive disease had significantly lower levels of all Ig classes and subclasses than patients with inactive disease: IgG, median 6.96 vs. 9.86 g/l, p=0.0001; IgA, median 0.63 vs. 1.53 g/l, p<0.0001; IgM, median 0.36 vs. 0.57 g/l, p=0.0035. After treatment, median IgA increased from 0.59 g/l to 0.74 g/l (p=0.0031). Other Ig classes and...
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The Role of Nurse of Patient after Kidney Transplantation
ŠEVČÍKOVÁ, Tereza
The diploma thesis sets two goals: 1. To find out the role of the nurse in postoperative care of a patient after a kidney transplant. 2. To map the specifics of nursing care for patients after kidney transplantation. Therefore, in order to meet the goals, four research questions were set: 1. What is the role of the nurse in postoperative care of a patient after a kidney transplant? 2. How does the role of a nurse in the postoperative period in a patient after a kidney transplant differ from postoperative care of the patient to another abdominal operation? 3. How does the role of a nurse in the postoperative period differ in a kidney transplant patient after another abdominal surgery in the standard ward and in the ICU? 4. What are the differences in the postoperative nursing care of a patient after a kidney transplant and the postoperative care of a patient after another abdominal surgery in the first days after the operation? The theoretical part of the work is divided into individual chapters, which describe the history and development of kidney transplantation, indications and contraindications of kidney transplantation, organ donation and inclusion on the waiting list, surgical techniques of transplantation and postoperative complications, immunosuppression and specifics of postoperative care and the effect of transplantation on pregnancy. Furthermore, the theoretical part deals with the history and modern view of the roles of nurses, the relationship between nurse and patient and finally the role of nurses in surgical fields. The practical part of the diploma thesis is processed by a qualitative method in the form of a semi-structured interview. The interview was conducted on the basis of pre-prepared questions with ten general nurses working in the inpatient department and intensive care unit of Transplant Surgery at IKEM. The analysis of the interviews took place in the form of "paper-pencil" and the method of open coding. All interviewed nurses refused to record the interviews in the form of an audio recording, which was respected. The results were divided into categories. The work should provide a comprehensive view of patient care in the postoperative period after kidney transplantation, describe its complexity and the differences between patient care after normal abdominal surgery and after transplantation. It can be used as a teaching material.
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Metabolic and genetic risks of development of non-alcoholic fatty liver disease in patients after liver transplantation and its impact on patient and graft survival
Míková, Irena ; Trunečka, Pavel (advisor) ; Červinková, Zuzana (referee) ; Brůha, Radan (referee)
Nonalcoholic fatty liver disease (NAFLD) occurs frequently not only in the general population, but also in liver transplant (LT) recipients. The data about prevalence, evolution, causes and significance of steatosis in patients after LT are limited. In a large retrospective study in LT recipients with histological evaluation of steatosis, we found high prevalence of steatosis (56,4 %) and steatohepatitis (10,4 %), the prevalence of steatosis increased after LT. Pretransplant predictors of steatosis included alcoholic cirrhosis and high BMI, whereas increased alkaline phosphatase and mycophenolate mofetil given initially were protective. Posttransplant predictors of steatosis included BMI, serum triglycerides, alcohol consumption and presence of type 2 diabetes mellitus, whereas increased serum creatinine was protective. Presence of significant steatosis/steatohepatitis was not associated with increased grade of fibrosis. There was no difference between the occurrence of steatosis in surviving and lost grafts. Survival of patients with/without significant steatosis was similar with a trend to higher long-term mortality of patients with significant steatosis. In the evaluation of the impact of TM6SF2 rs58542926 and PNPLA3 rs738409 genotypes of the donor and recipient on pathophysiology of steatosis...
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Methods for detection of impaired immune response in cardiac-surgical patients
Kormundová, Nikola ; Koláčková, Martina (advisor) ; Filipp, Dominik (referee)
In patients after cardiac surgery, there is an increase in the level of molecules with both pro-inflammatory and anti-inflammatory effects. This increase is influenced by the patient's clinical condition, but also by the nature of the operation itself, which uses conventional extracorporeal circulation. This technique leads to damage to blood elements by direct contact with air and parts of the extracorporeal circulation, as well as to ischemia-reperfusion injury. The specifics of cardiac surgery then affect possible postoperative complications such as multiorgan failure or septic shock. The diploma thesis is divided into a theoretical and a practical part. The theoretical part describes the principle and influence of cardiopulmonary bypass on the human body and the complications that are associated with its use. Furthermore, IFN-γ is described herein as a potential marker of septic conditions that could reflect the clinical postoperative condition of patients. The practical part of the diploma thesis monitored the percentage change of selected cell populations and the production of IFN-γ in the peripheral blood of patients before and after cardiac surgery. Furthermore, the response of individual isolated populations of healthy volunteers to selected stimulators was investigated. The percentage of...
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The role of macrophages in immunosuppression mediated ny regulatory T cells
Kadlecová, Kristýna ; Holáň, Vladimír (advisor) ; Stříž, Ilja (referee)
Regulatory T cells (Treg) represent one of the most important mechanisms of immunoregulation. Treg suppress immune reactions and prevent overactivation of the immune system. There is a lot of ways of Treg action described, here we have focused on Treg interference with macrophages. The suppressor capacity of a highly purified Treg population was demonstrated in proliferation assays. The level of suppression of effector T cell proliferation differs depending on the presence of macrophages in the culture. Treg suppression has been significantly higher in the presence of macrophages. These observations led to hypotesis that Treg affect directly macrophages. However, using flow cytometry, reduction of expression of costimulatory molecules on macrophages after culture with Treg was not observed. Macrophages precultured with Treg showed a comparable functionality as macrophages cultured alone. Neither flow cytometry nor live cell imaging revealed any cytotoxic activity of Treg towards macrophages. Despite the presence of macrophages, Treg did not suppress effector cell proliferation in a model, where stronger activation of effector cells was induced. Therefore, a new hypothesis was presented - initially observed higher suppression in the presence of macrophages was probably caused by a qualitatively or...
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Interaction between NKT and myeloid derived suppressor cells and antitumour immunity
Straňavová, Lucia ; Reiniš, Milan (advisor) ; Holáň, Vladimír (referee)
Myeloid- derived suppressor cells (MDSCs) are a heterogeneous population of cells, which plays an important role in the suppression of anti-tumor immune responses. NKT cells represent an additional heterogeneous cell population that plays a crucial role in the regulation of immune responses. It shows that MDSCs and NKT cells may be similar to other populations imunoregulatory cells interact with each other and influence their functions. These interactions are important regulatory factor that may contribute to activation and to suppress anti-tumor immunity. Through interactions with type I NKT cells could differentiate these immunosuppressive MDSCs to immunogenic APC, which could form the basis for immunotherapeutic vaccine. All interactions between the NKT and MDSCs but have a positive effect of imunoregulatory. Interaction between MDSCs and CD4 + NKT cells II. type are immunosuppressive and may subsequently suppress the activity of cytotoxic T-lymphocyte (CTL). In some tumor models it was found that the immunosuppressive nature may also be interactions between MDSCs and type I NKT cells He had, however, alleviate the use of all-trans-retinol acid (ATRA), which induces differentiation of MDSCs.
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Huntington's disease modeling and stem cell therapy in spinal cord disorders and injury
Hruška-Plocháň, Marián ; Motlík, Jan (advisor) ; Bjarkam, Carsten (referee) ; Roth, Jan (referee)
Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...
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The effect of immunosupression on cell therapy in mouse model of Alzeimer's disease
Gajdoš, Roman ; Jendelová, Pavla (advisor) ; Chmelová, Martina (referee)
Alzheimer's disease is a chronic, progressive, neurodegenerative disease. It belongs to the most common type of dementia and worldwide it is statistically the fifth cause of mortality. The most common morphological markers are insoluble β amyloid plaques, hyperphosforylated tau proteins and formation of neurofibrilar tangles. Among the manifestations of the disease is amyloid angiopathy, synaptic transmission disorders and subsequent apoptosis, deterioration of cognitive functions and brain atrophy. Studies have shown that administration of mesenchymal stem cells (MSC) has an immunomodulatory effects and it can reduce the production and storage of β amyloid and thus improve cognitive functions. In preclinical studies, which are conducted in transgenic mice and often use xenografts, administration of immunosuppresion may lead to variety of positive or negative effects which can affect the results of the experiment. The subject of the master's thesis was to determine the effect of immunosuppression on experimental therapy with MSC in various time windows of AD progression (model 3xTg). At which scale and combination of immunosupression will influence the cell therapy's effects, the length of graft survival, mortality of experimental animals and changes at the cellular level. We have also assessed...
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