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Non-coding RNA in hepresvirus infection
Pelák, Ondřej ; Drda Morávková, Alena (advisor) ; Holá, Dana (referee)
MiRNAs are endogenous short RNAs that are well conserved in eukaryotic organisms and are thought to be a vital and evolutionarily ancient component of genetic regulation. Their key role is in post-transcriptional regulation of gene expression. Some viruses were able to utilize the capabilities of these tiny RNAs to regulate their own gen expression or to regulate host gene expression in use of avoidance from immunity answers to their presence. Among these viruses belongs also the Herpesviridae family. Members of this family are using miRNA in various ways, from regulation of their own gene expression to targeting host mRNA, which prevents translation of factors related to immune answers. This work is intent on biogenesis of miRNA, its mechanism, function and manner in which it is used by representatives from Herpesviridae family.
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Research of protective immunity on patients after transplantation.
Pelák, Ondřej ; Kalina, Tomáš (advisor) ; Drda Morávková, Alena (referee)
Depletion of immune functions in patients after hematopoetic stem cell transplantation (HSCT) results in higher frekvencies of several types of oportunistic infections. Especially the reactivation of human cytomegalovirus (CMV) may cause life-threating infections and require antiviral treatment. Within this diploma thesis we compare the function signatures of CD4+ and CD8+ T-cells stimulated by CMV antigens, which were obtained from 63 pacients after HSCT. Polychromatic flow cytometry measurements of CD154 (CD40L), intracellular cytokines (INF-γ and IL-2) and marker of degranulation (CD107a) allowed us to determine the function status of various T-cells simultaneously. We have discovered, that dual production of INF-γ and IL-2 on CD8+ T-cells was present only in pacients controling their CMV reactivations, but was absent in noncontrolers. Single production of INF-γ on CD8+ T-cells was the most abundat subtype, but they most probably represent non-protective memory cells. We have further created two test of NK-cells functionality, one that aims on the detection of their degranulation ability and second, that detects cytotoxic capability of NK-cells. Key words: transplantation, hematopoetic stem cells, T-lymfocytes, immune system recovery, cytomegalovirus, INF-γ, IL-2
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Specific anti-viral immunity in immunocompromised patients, not only after bone marrow transplantation
Pelák, Ondřej
Viral reactivations after hematopoietic cell transplantation contribute to significant morbidity and mortality. Timely immune reconstitution of functional T cell immunity is crucial in controlling these viral reactivations. In this thesis we were able to identify several functional T cell populations, which are responsible for fast resolution of viral reactivation. Appearance of some of these populations may be even used for prediction of the occurrence of viral reactivation. On the other hand, the administration of corticoids due to the treatment of graft versus host disease contributes as significant negative predictor to viral reactivation incidence. We are also offering an option of adoptively transferred virus specific T cells for patients suffering from prolonged virus complications, through identification of suitable donors by two different methods. Viral reactivations cause complication also in patients who underwent the solid organ transplantation. In this thesis we have found the connection between allo and virus specific T cells. We have successfully identified several cross-reactive T cell clones which have responded to both allo and viral stimulation. Further it seems that these clones may play an important role in rejection of transplanted kidney if there is also present an ongoing T...
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Specific antiviral immunity in immunocompromised patients, not only after bone marrow transplantation
Pelák, Ondřej ; Kalina, Tomáš (advisor) ; Lysák, Daniel (referee) ; Němečková, Šárka (referee)
-3- SUMMARY Viral reactivations after hematopoietic cell transplantation contribute to significant morbidity and mortality. Timely immune reconstitution of functional T cell immunity is crucial in controlling these viral reactivations. In this thesis we were able to identify several functional T cell populations, which are responsible for fast resolution of viral reactivation. Appearance of some of these populations may be even used for prediction of the occurrence of viral reactivation. On the other hand, the administration of corticoids due to the treatment of graft versus host disease contributes as significant negative predictor to viral reactivation incidence. We are also offering an option of adoptively transferred virus specific T cells for patients suffering from prolonged virus complications, through identification of suitable donors by two different methods. Viral reactivations cause complication also in patients who underwent the solid organ transplantation. In this thesis we have found the connection between allo and virus specific T cells. We have successfully identified several cross-reactive T cell clones which have responded to both allo and viral stimulation. Further it seems that these clones may play an important role in rejection of transplanted kidney if there is also present an ongoing...
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Research of protective immunity on patients after transplantation.
Pelák, Ondřej ; Kalina, Tomáš (advisor) ; Drda Morávková, Alena (referee)
Depletion of immune functions in patients after hematopoetic stem cell transplantation (HSCT) results in higher frekvencies of several types of oportunistic infections. Especially the reactivation of human cytomegalovirus (CMV) may cause life-threating infections and require antiviral treatment. Within this diploma thesis we compare the function signatures of CD4+ and CD8+ T-cells stimulated by CMV antigens, which were obtained from 63 pacients after HSCT. Polychromatic flow cytometry measurements of CD154 (CD40L), intracellular cytokines (INF-γ and IL-2) and marker of degranulation (CD107a) allowed us to determine the function status of various T-cells simultaneously. We have discovered, that dual production of INF-γ and IL-2 on CD8+ T-cells was present only in pacients controling their CMV reactivations, but was absent in noncontrolers. Single production of INF-γ on CD8+ T-cells was the most abundat subtype, but they most probably represent non-protective memory cells. We have further created two test of NK-cells functionality, one that aims on the detection of their degranulation ability and second, that detects cytotoxic capability of NK-cells. Key words: transplantation, hematopoetic stem cells, T-lymfocytes, immune system recovery, cytomegalovirus, INF-γ, IL-2
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Non-coding RNA in hepresvirus infection
Pelák, Ondřej ; Holá, Dana (referee) ; Drda Morávková, Alena (advisor)
MiRNAs are endogenous short RNAs that are well conserved in eukaryotic organisms and are thought to be a vital and evolutionarily ancient component of genetic regulation. Their key role is in post-transcriptional regulation of gene expression. Some viruses were able to utilize the capabilities of these tiny RNAs to regulate their own gen expression or to regulate host gene expression in use of avoidance from immunity answers to their presence. Among these viruses belongs also the Herpesviridae family. Members of this family are using miRNA in various ways, from regulation of their own gene expression to targeting host mRNA, which prevents translation of factors related to immune answers. This work is intent on biogenesis of miRNA, its mechanism, function and manner in which it is used by representatives from Herpesviridae family.
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