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Cellular factors restricting mouse polyomavirus infection in host cells: Studies of PML protein isoforms
Anderová, Karolína ; Forstová, Jitka (advisor) ; Němečková, Šárka (referee)
Promyelocytic leukaemia nuclear bodies (PML NBs) are multifunctional nuclear spherical structures formed by the PML protein shell and other interaction partners that have been described to be involved in many cellular processes and immune defences. In the antiviral immune response, PML NBs and their components act as direct restriction factors as well as in the regulation of the interferon response. On the other hand, viruses have developed antagonistic mechanisms to resist this inhibition. This work deals with the role of PML NBs in infection with model Murine polyomavirus (MPyV) and focuses on the study of PML protein isoforms. The first aim of the work was to analyse the formation of human (hPML) and mouse (mPML) NBs in a mouse embryonic fibroblast (MEF) model. Subsequently, the localization of hPML and mPML NBs during infection was determined. Close localization with viral replication centres was observed for both PML species. In the next step, the effect of infection or interferon α (IFNα) on mPML protein expression was tested. Infection and treatment with IFNα led to an increase in mPML expression at the level of both gene transcription and protein synthesis. At the same time, the data indicated the largest increase in transcription of the mPML3 isoform. The work also addressed the potential...
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Induction of innate immune response against intracellular bacterium Francisella tularensis
Sommerová, Gabriela ; Konečná, Klára (advisor) ; Myslivcová Fučíková, Alena (referee)
Background: The purpose of this bachelor thesis is to describe Francisella tularensis and activation of innate immunity during host infection. Main findings: The main findings of the work include the method of recognition of F. tularensis via Toll-like receptors, the production of cytokines and chemokines and the subsequent involvement of other components of innate immunity, including neutrophils, NK cells, or humoral components of the immune response, which also includes complement. The information is based on a number of studies performed mainly on mouse models. Conclusions: The intracelullar bacterium F. tularensis is known to cause tularemia. Its high infectivity, together with the high risk of death in the lung form, raises great concerns about the misuse of this bacterium as a biological weapon. To date, not all of its mechanisms of pathogenesis are known, which is a major problem in the development of effective vaccines. The induction of innate immunity appears to be very important in the host's defense against F. tularensis. However, despite several decades of research, the mechanisms of F. tularensis involved in host cell manipulation, including the regulation of the induction of immune response to F. tularensis infection, have still not been fully elucidated. Key words: Francisella...
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Induction of innate immune response against intracellular bacterium Francisella tularensis
Sommerová, Gabriela ; Konečná, Klára (advisor) ; Myslivcová Fučíková, Alena (referee)
Background: The purpose of this bachelor thesis is to describe Francisella tularensis and activation of innate immunity during host infection. Main findings: The main findings of the work include the method of recognition of F. tularensis via Toll-like receptors, the production of cytokines and chemokines and the subsequent involvement of other components of innate immunity, including neutrophils, NK cells, or humoral components of the immune response, which also includes complement. The information is based on a number of studies performed mainly on mouse models. Conclusions: The intracelullar bacterium F. tularensis is known to cause tularemia. Its high infectivity, together with the high risk of death in the lung form, raises great concerns about the misuse of this bacterium as a biological weapon. To date, not all of its mechanisms of pathogenesis are known, which is a major problem in the development of effective vaccines. The induction of innate immunity appears to be very important in the host's defense against F. tularensis. However, despite several decades of research, the mechanisms of F. tularensis involved in host cell manipulation, including the regulation of the induction of immune response to F. tularensis infection, have still not been fully elucidated. Key words: Francisella...
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Antimicrobial and antiborrelial characterization of Dermacentor marginatus defensin.
CHRUDIMSKÁ, Tereza
Ticks, as blood sucking arthropods, are able to transmit various pathogens. Their immune system involves many antimicrobial molecules to fight against them. Among these antimicrobials, defensins, a 5.3 kDa peptides, play an important role in rapid immune answer. In this study we examined the antimicrobial spectrum of Dermacentor marginatus defensin (def DM) with respect to the fact that Dermacentor variabilis ticks are not able to successfully maintain and transmit Borrelia burgdorferi sensu lato, the causative agent of Lyme disease. Expression of the def DM gene was detected in hemolymph, midgut and salivary glands. Defensin was isolated from hemolymph using RP-HPLC and its sequence was determined by mass spectrometry and Edman degradation. Synthetic mature peptide def DM revealed an anti-Gram-positive bacterial role as well as borreliacidal activity, with concentration dependent influence. These results suggest a possible role in the clearing of borrelia spirochetes ingested by D. marginatus ticks.
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The role of monocytes in pathogenesis of diabetes - immunogenetic study
Paukner, Karel ; Daňková, Pavlína (advisor) ; Černá, Marie (referee)
Type one diabetes is an autoimmune disease. It is caused by the destruction of β cells of Langerhans' pancreatic islets. Hyperglycemia is a major symptom of β cell destruction. Monocytes play a key role during T cell activation. T cell effect can be protective (Treg) or destructive. Monocyte destroys β cells as a macrophage and generates self-tolerance as a dendritic cell. The number of patients with T1D is increasing. In the presented work I aim to summarize current information about pathogenesis of T1D and I try to propose future way of research.
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The use of artificial opsonization for cancer treatment
PRIMASOVÁ, Hedvika
This work is using the innate immunity to fight against cancer. Artificial opsonization of B16-F10 mice melanoma cancer cells was studied in vivo and in vitro. For this purpose, syngeneic mice IgG was isolated and the linkage to cancer cells was provided using bifunctional crosslinker SMCC. Survival analysis was evaluated for the in vivo experiment and spectrophotometric and fluorometric methods were used to investigate the extent of the linkage of protein on B16-F10 cells via SMCC. The extent was evaluated using regression lines of corresponding compounds. In vivo and in vitro results were compared.
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