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Significance of the major histocompatibility complex for organ transplantation
Ilina, Liudmila ; Slavčev, Antonij (advisor) ; Grobárová, Valéria (referee)
The major histocompatibility system is a region in the human genome located on chromosome 6. HLA genes encode polymorphic cell-surface glycoproteins which are primarily responsible for presentation of self and non-self antigens to T cells. When the T lymphocyte recognizes the MHC-peptide complex as foreign, it activates effector components of the innate and adaptive immune system. Therefore, mismatched HLA antigens can lead to a strong immune response against the donor's tissue. HLA laboratories support transplant programs by evaluation the HLA matching between patients and their potential donors and, based on these data, assist in the evaluation of the risk of rejection and eventual immunological complications after transplantation. The aim of this thesis is to describe the significance of the major histocompatibility complex for the occurrence of cellular and antibody-mediated rejection after solid organ transplantation and discuss the relationship between the degree of HLA matching and graft survival outcomes. Key words HLA, organ transplantation, rejection
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Auditory evoked potentials and its sensing
Němečková, Pavla ; Svačinová, Jana (referee) ; Kolářová, Jana (advisor)
This thesis deals recording evoked potentials. The TruTrace EMG was used for the recording and data was collected from 10 volunteers. For a better understanding of this is issue, is explained auditory system, recording methods, stimulation pulses and stimulation headphones at first. The main goal of the thesis is to compare the current averaging method with the newly created method. The results from both methods were compared based on their standard error of the mean. Bayesian averaging, new method, was more successful in 65 % than the pre-set rejection method.
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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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The role of IL-17 in kidney transplantation
Menšíková, Markéta ; Stříž, Ilja (advisor) ; Krulová, Magdaléna (referee)
The role of IL-17 in kidney transplantation - abstract Naive CD4+ T-lymphocytes (Thp) can develop into Th17 line in the presence of TGF- and IL-6. Th17 cells are characterized by expression of Ror- t and by production of interleukin-17 (IL-17). It is secreted as a glycoprotein homodimer. Binding to IL-17 receptor (IL-17R), which is present in all cell types, stimulates the production of proinflammatory cytokines and chemokines. The ratio of Th17: Treg in the graft showing signs of rejection is higher than in the graft without rejection. The presence of IL-17 in a culture of proximal tubular epithelial cells (PTEC) stimulates the production of IL-6, IL-8, MCP-1 and C3 complement component. Simultaneous action of IL-17 and CD40L synergistically increases the production of IL-6, IL-8 and RANTES. Signaling from the receptor on the surface of PTEC associated with its increased expression is effected via the src kinase and MAP kinase, and probably leads to the transcription factor NF- B. In rat models of transplantation, the IL-17 appears in allografts on the second day after surgery, the level rises until the fifth day, then decreases and disappears before the death of the animal. IL-17 is not detectable in isografts and negative controls. It appears before the IFN- , which had been considered a trigger of...
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ELISpot methodology and prediction of acute rejection after renal transplantation.
Rybáková, Kateřina ; Slavčev, Antonij (advisor) ; Mrázek, František (referee)
Transplantation is the best therapeutic solution for patients with chronic renal failure. Due to the great advances in immunosuppressive therapy in the last decades, graft and patient survival have improved significantly. On the other hand, immunosuppressive therapy has serious side effects - too strong immunosuppression may lead to infection or malignancies, conversely insufficient immunosuppression may lead to graft rejection. Due to the grave consequences of acute rejection, the main goal of cooperation of clinicians and transplant immunologists is to stratify patients into groups with low, moderate and high risk of rejection based on the evaluation of various immunologic risk factors. There are reports in the literature that the numbers (frequencies) of interferon gamma (IFNγ) producing cells before transplantation may be helpful to identify patients with high risk of acute cellular rejection and to predict long-term survival of the graft. In this retrospective study we determined the pre-transplant frequencies of activated donor specific T lymphocytes producing IFNγ after short stimulation (24 hrs) by ELISpot (Enzyme-linked immunosorbent spot assay). The results were correlated with the incidence of acute cellular (ACR) and antibody-mediated (AMR) rejection and with other risk factors. In our...
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The role of memory T cells in transplant immunity
Straňavová, Lucia
Memory T cells represent a specific subpopulation of cells formed during the first encounter with antigen. The main role of these cells is to elicit faster and more effective secondary response during reinfections. In transplant immunity, they may affect graft survival directly with donor-specific memory T cells or with cross-reactive virus-specific memory T cells. In this study, we focused on donor-specific and CMV-specific memory/effector T cells. We were interested in the effect of immunosuppressive therapy on the frequency of these cells in periphery. We found that the immunosuppression, prophylaxis and length of dialysis did not significantly affect the number of CMV-reactive cells 6 months after transplantation. We were also interested in the cross-reactivity between CMV and donor antigens, so-called heterologous immunity, which we verified by analyzing the TCR-β repertoire using next- generation sequencing (NGS) in CMV and donor-reactive T cells. Functional cross-reactive T cell clones (shared the same TCR-β sequence) were then found both in the peripheral blood of pre-transplant patients and in the post-transplant graft biopsy. We were also interested if long-term dialysis treatment affects immune memory. Dialysis therapy is often associated with the presence of poorly defined immune system...
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Markers of transplantation tolerance in kidney transplantation
Krepsová, Eva ; Viklický, Ondřej (advisor) ; Krejčí, Karel (referee) ; Živný, Jan (referee)
Long-term renal graft acceptance still requires long-term immunosuppressive therapy, which is accompanied by many adverse effects. Contrarily insufficient immunosuppression could lead to graft rejection and its failure. Therefore, research continues for biomarkers that reflect a patient's immunological status and thus allowing for individualized immunosuppressive therapy. In our study we showed lower incidence of acute rejection in kidney transplant recipients treated with rabbit anti-thymocyte globulin (rATG) or basiliximab induction within the first three months after transplantation. The rATG induction caused profound decrease of recipient's peripheral blood T and NK cells, as well as transcripts that are exclusively expressed by these cell types together with expansion of regulatory T cells (Tregs) among CD4+ T cells. In rATG group the increase of two transcripts associated with rejection (MAN1A1 and TLR5) was also observed in early post-transplant period. After the basiliximab induction we transiently detected CD4+CD25low/-FoxP3+ cell population along with disappearance of CD4+CD25+FoxP3+ Tregs. Basiliximab induction resulted in a transient increase in CD4+FoxP3+ Tregs, accompanied by the highest peripheral expression levels of markers associated with operational tolerance (FOXP3 and TCAIM)....
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The role of memory T cells in transplant immunity
Straňavová, Lucia ; Viklický, Ondřej (advisor) ; Zajícová, Alena (referee) ; Vlas, Tomáš (referee)
Memory T cells represent a specific subpopulation of cells formed during the first encounter with antigen. The main role of these cells is to elicit faster and more effective secondary response during reinfections. In transplant immunity, they may affect graft survival directly with donor-specific memory T cells or with cross-reactive virus-specific memory T cells. In this study, we focused on donor-specific and CMV-specific memory/effector T cells. We were interested in the effect of immunosuppressive therapy on the frequency of these cells in periphery. We found that the immunosuppression, prophylaxis and length of dialysis did not significantly affect the number of CMV-reactive cells 6 months after transplantation. We were also interested in the cross-reactivity between CMV and donor antigens, so-called heterologous immunity, which we verified by analyzing the TCR-β repertoire using next- generation sequencing (NGS) in CMV and donor-reactive T cells. Functional cross-reactive T cell clones (shared the same TCR-β sequence) were then found both in the peripheral blood of pre-transplant patients and in the post-transplant graft biopsy. We were also interested if long-term dialysis treatment affects immune memory. Dialysis therapy is often associated with the presence of poorly defined immune system...
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Auditory evoked potentials and its sensing
Němečková, Pavla ; Svačinová, Jana (referee) ; Kolářová, Jana (advisor)
This thesis deals recording evoked potentials. The TruTrace EMG was used for the recording and data was collected from 10 volunteers. For a better understanding of this is issue, is explained auditory system, recording methods, stimulation pulses and stimulation headphones at first. The main goal of the thesis is to compare the current averaging method with the newly created method. The results from both methods were compared based on their standard error of the mean. Bayesian averaging, new method, was more successful in 65 % than the pre-set rejection method.
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