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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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The immune response of naïve mice infected with the neuropathogenic schistosome Trichobilharzia regenti
Macháček, Tomáš ; Horák, Petr (advisor) ; Bilej, Martin (referee) ; Schabussova, Irma (referee)
Helminth neuroinfections represent a serious health issue, but the mechanisms of the host immune response often remain neglected despite the fact they might contribute to pathogenesis. This is partly due to the unavailability of clinical samples and the lack of suitable laboratory models. Herein, I focused on the characterization of several aspects of the immune response of mice infected with the neuropathogenic avian schistosome Trichobilharzia regenti. After the percutaneous infection of mice (accidental hosts), most T. regenti schistosomula are entrapped and eliminated in the skin, but the parasite antigens initiating the protective immune reaction are not known. Our in vitro experiments revealed that T. regenti cathepsin B2, a cysteine peptidase used for the skin penetration, activates bone marrow-derived dendritic cells much stronger than the parasite homogenate, suggesting its role in initiating the mixed type1/2 host immune response. However, some schistosomula manage to escape from the skin and continue their migration to the spinal cord. Here they crawl preferentially within the white matter which we demonstrated by the robust 3D imaging techniques, ultramicroscopy and micro-CT. The invasion of the spinal cord is accompanied by striking hypertrophy of astrocytes and microglia. We showed...
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Immune response against skin-penetrating helminths with a focus on schistosomes
Revalová, Alena ; Macháček, Tomáš (advisor) ; Leštinová, Tereza (referee)
Breaching the vertebrate skin and overcoming the local immunity represents a critical step in the life cycles of many helminths. This bachelor thesis summarized the current knowledge of the skin immune response against schistosomes. Both innate and adaptive immune mechanisms are activated soon after the infection. Despite certain differences between mice and humans, complement, granulocytes and especially CD4+ T-lymphocytes are considered as key players in anti-schistosomal immunity of both species. However, several aspects of the host immune response, such as the initial source of cytokine IL-4, IL-10 or expression pattern of certain co- receptors remain unclear and warrant further research. A comprehensive understanding of the host immune response in the skin as well as the respective parasite immune evasion strategies is needed to boost vaccine development. Keywords: immune response, skin, lymph nodes, helminths, schistosomes
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Hematopoiesis in the models of zebrafish and medaka as a recipient for human HSC xenograft
Pravcová, Naďa ; Drbal, Karel (advisor) ; Svoboda, Ondřej (referee)
Danio rerio (zebrafish) and Oryzias latipes (medaka) have recently become popular model organisms to study hematopoiesis. These model organisms present several advantages in comparison to other commonly used models, the most common being Mus musculus (mouse). The advantages are shorter generation time, large offspring production, frequent spawning, external fertilization and development, the optical transparency of embryos amenable to genetic manipulation on the background of vast numbers of transgenic lines (mainly in zebrafish) and inbred strains (in medaka). Moreover, most of the mechanisms behind zebrafish and medaka hematopoiesis are conserved in higher vertebrates. Most importantly, the optical transparency in early development and in adult mutant transparent strains allows for observation of hematopoietic stem cell (HSC) development in vivo. Therefore, it is possible to generate humanized fish using xenotransplanted human HSCs for studies of the engraftment, differentiation, and trafficking of human HSC in vivo. Currently, the most popular organism for human HSC xenotransplantation is mice. This model system is not suitable for in vivo imaging of HSC engraftment. Moreover, a prior immunodepletion step is necessary. The process of immunodepletion includes genetic manipulation or irradiation...
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Interactions of human immune system with saliva of bloodfeeding Nematocera
Jelínková, Kristýna ; Kolářová, Iva (advisor) ; Janda, Jozef (referee)
In humans, the bites of bloodfeeding insects from the suborder Nematocera induce an immune reaction, both humoral and cell-mediated. Some antigens presented in the saliva of some insect families - Psychodidae, Culicidae, Simuliidae and Ceratopogonidae - are studied more deeply to reveal their immunomodulatory and antigennic properties. Most studies are focused on mosquitos (Culicidae) and sand flies (Psychodidae). Mosquito saliva elicits primarily IgG and IgE antibodies. The level of antibodies in the sera of bitten individuals reflects the length and intensitity of previous exposure to insect bites. Anti-saliva IgE antibodies play an important role in response to the mosquito bites and are frequently associated with allergic reactions. On the other hand, sand fly saliva elicits primarily IgG antibodies. Cell-mediated human immune response to mosquito bites is a neglected research topic. It has been proven that the saliva of sand flies (genus Phlebotomus and Lutzomyia) stimulates proliferation of PBMC from repeatedly bitten humans. Cytokine production by human PBMC and expression of costimulatory molecules in human monocytes, macrophages, and dendritic cells are also influenced by the presence of sand fly saliva. So far as we know, there are only few studies on human immune response to black fly...
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Analysis of cell-free nucleic acids and its potential clinical application.
Pazourková, Eva ; Korabečná, Marie (advisor) ; Drábek, Jiří (referee) ; Vodička, Radek (referee)
This work presents the results ofour research of cell-free nucleic acids (cfNA). The first part shows changes in methylation patterns of immune response genes promoters that are detectable in plasma during the hemodialysis sessions and also differences in methylation between patients and healthy subjects. Alterations include genes that play their role in the regulation of hematopoiesis and these changes are in close relation with the need of anemia therapy. In the other plasma cfNA study we detected miRNA signatures in patients with acute myeloid leukemia at diagnosis (6 highly abundant miRNAs found) and in remission achieved after standard chemotherapy (trend to n01malization, lower levels ofthese miRNAs). Another part of work presents data from the study of potential non-invasive biomarker of bladder cancer. The amounts of cfDNA in urine are higher in patients than in healthy subjects and there were found 5 down-regulated miRNAs. Simultaneously it was established set of 30 miRNAs that are constantly present in urine supematants independently on sex, age and healthy status of subjects. The last part presents analysis ofcell-free fetal DNA. We analyzed differences between a new quantification method - droplet digital PCR and real-time PCR which is used routinely nowadays. Slightly more precise was...
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STUDIUM ZÁKLADNÍCH MECHANISMŮ PERITONEÁLNÍHO ZÁNĚTU U CANDÁTA OBECNÉHO (Sander lucioperca)
CHÁBERA, Jan
Pike-perch (Sander lucioperca) is a species of fish whose breeding in recirculation systems has a great prospect in the years to come. Due to the unfavorable conditions of intensive rearing of these fish in recirculation systems, they are often exposed to stress resulting in reduced fish defenses. Thus, fish are exposed to attack of a wide range of bacteria. Although there are preventive measures to protect fish against pathogen attack, knowledge of the immune system and the immune response of the fish is crucial for further evolution of vaccination. Even though we know the mechanisms of immune response of many fish species,but the knowledge of the pike-perch's immune response is very limited.
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Imunomodulační účinky extraktů z helminta na střevní buněčnou linii potkaního modelu
LEVÁ, Jana
In this study, we examined the immunomodulatory effect of excretory/secretory products, crude adult extracts and crude larvae extracts from Hymenolepis diminuta on the intestinal epithelilal cell line from a rat. For determination of the immunomodulation effect of all H. diminuta extracts was used relative gene expression of TNFa, IL-17re and IL-33 from epithelial cells and it was tested using real-time PCR. Our result showed that excretory/secretory products had the strongest antiinflammatory effect on the epithelial cells. We assume that crude adult extracts play an important role in increase of gene expression of IL-33 and also in the immunomodulatory ability of H. diminuta in the host organism.
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GENE EXPRESSION AND IMMUNOLOGICAL RESPONSE IN MICE EXPOSED TO ZnO NANOPARTICLES
Rössner ml., Pavel ; Vrbová, Kristýna ; Strapáčová, S. ; Rössnerová, Andrea ; Ambrož, Antonín ; Brzicová, Táňa ; Líbalová, Helena ; Javorková, Eliška ; Zajícová, Alena ; Holáň, Vladimír ; Kulich, P. ; Večeřa, Zbyněk ; Mikuška, Pavel ; Coufalík, Pavel ; Křůmal, Kamil ; Čapka, Lukáš ; Dočekal, Bohumil ; Šerý, Omar ; Machala, M. ; Topinka, Jan
We analyzed gene expression changes in the lungs and the immunological response in splenocytes of mice exposed by inhalation of ZnO nanoparticles - NP. Adult female ICR mice were treated for three days and three months, respectively. Analysis of differential expression in genes involved in oxidative stress was conducted using quantitative RT-PCR. The potential immunotoxic and immunomodulatory effects of ZnO NP were analyzed by phenotyping and cytokine production by splenocytes after three months exposure. Three days exposure resulted in down-regulation of GCLC, GSR, HMOX-1, NQO-1, NF-kB2, PTGS2 and TXNRD1 mRNA expression, three months exposure increased the expression of these genes. Three months exposure caused a significant decrease in the percentage of granulocytes in the spleen cells, and affected the production of IL-10 and IL-6 by lipopolysaccharide-stimulated leukocytes. In summary, our study revealed changes in the expression of genes involved in the oxidative stress response following acute ZnO NP exposure. Subchronic ZnO NP exposure induced immunomodulatory effects in the spleen.
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