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The Effect of Aire Deficiency on Antibody Responses Against TH17 Effector Cytokines and Candida albicans
Liberdová, Jana ; Dobeš, Jan (advisor) ; Schwarzer, Martin (referee)
The Autoimmune Regulator (Aire) is a well-known master regulator of central tolerance, promoting the expression of antigens restricted to peripheral tissues in the thymus. These antigens are presented to developing T cells, ensuring the elimination of self-reactive clones based on their ability to recognize them. Aire dysfunction leads to the development of multiorgan autoimmune pathologies and susceptibility to chronic mucosal fungal infections. The emergence of autoimmunity is largely explained by the disruption of the thymic regulation of peripheral antigen expression. However, the mechanisms underlying fungal infection susceptibility are much less understood. Mucosal anti-fungal immune defense in general primarily relies on the mobilization of TH17 cells and IgA antibodies. Defective cellular TH17 response and autoantibodies against TH17 effector cytokines observed in Aire deficiency are associated with higher susceptibility to fungal infection. However, the integrity of IgA response in Aire deficiency has not been addressed so far. In my thesis, I confirmed that Aire deficient mice develop elevated levels of autoantibodies against TH17 effector cytokines. These autoantibodies are not affected by experimental fungal colonization, suggesting that active fungal infection is not enhancing the...
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Induction of immune responses by intestinal segmented filamentous bacteria
Pacáková, Iva ; Dobeš, Jan (advisor) ; Schwarzer, Martin (referee)
The intestine is constantly exposed to a variety of pathogens, and therefore a proper function of the intestinal barrier is essential for the overall health of the body. Segmented filamentous bacteria are members of the gut microbiota residing in the terminal ileum of the small intestine, where they penetrate through the mucus layer and tightly associate with intestinal epithelial cells. This SFB association with the epithelium is accompanied by the formation of endocytic vesicles filled with an antigen that triggers the IgA production in the intestine and the Th17 cell dependent immune response. There are two steps for the induction of Th17 cells. First, SFB-dependent induction of Th17 cells requires antigen presentation by MHC class II molecules. Therefore, antigen-presenting cells migrate to the site of induction in mesenteric lymph nodes and prime antigen-specific naive T cells to become RORγt+ pre-Th17 T cells. Secondly, activated T cells migrate back to the lamina propria, where they undergo functional maturation by triggering cytokine production. As a result, Th17 cells accumulate in lamina propria, where they produce their effector cytokines IL-17 and IL-22, further affecting the gut's overall balance. However, the extensive Th17 polarization induced by SFB may subsequently contribute to...
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Capacity of probiotics to affect innate lymphoid cells type 3
Věcek, Jan ; Hrdý, Jiří (advisor) ; Schwarzer, Martin (referee)
Innate lymphoid cells type 3 (ILC3) are a group of relatively newly discovered lymphocytes that lack an antigen-specific receptor. Nevertheless, their important role of immune regulators on mucous membranes is evident. In addition to the development of lymphoid tissue in embryogenesis, and during ontogenesis, postnatally, ILC3 are mainly involved in maintaining intestinal homeostasis and controlling intestinal microbiota. ILC3 produces various cytokines that stimulate surrounding intestinal cells to produce antimicrobial peptides and maintain epithelial wall integrity. The major cytokine produced by ILC3 is IL-22. Th17 lymphocytes and ILC3 are similar in many respects but differ significantly in some functions. ILC3 can regulate adaptive immunity cells towards an antimicrobial response without inducing inflammation. They are also directly connected to cells of the nervous system. Some probiotic bacterial strains produce metabolites that directly affect ILC3. This mechanism could be used in new therapeutic approaches to ameliorate the severity of diseases where changes in microbiota composition and function are inducing proinflammatory responses of the host. Key words: innate lymphoid cells; IL-22; antimicrobial peptides; probiotics; microbiota
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Study of the materno-fetal microchimerism of the APC using MHCII/EGFP mouse model and clearing histological techniques
Knížková, Karolina ; Černý, Jan (advisor) ; Schwarzer, Martin (referee)
Microchimerism arises from the exchange of cells between genetically distinct individuals. The coexistence of genetically distinct cell populations within a single organism has possible effects on health and functioning of individuals immune systems, but the exact mechanisms of action are often not yet known. With the development of microscopic technologies and software for data analysis, the possibilities of detection and phenotyping of these rare cell populations are expanding. My intention in this work is to find maternal microchimerism in embryonic tissues (E13) and intestines of breastfed pups using MHCII/EGFP knock-in mouse model. Several different technologies potentially suitable for the detection of maternal microchimeric cells in offspring tissues (light sheet fluorescent microscopy - LSFM, virtual slide microscopy and flow cytometry) were selected. Advanced analysis of the obtained samples from the light sheet microscopy using the creation of a neural network was used here. The presence of maternal microchimerism was not demonstrated by flow cytometry. Using LSFM, image data were obtained from intestinal samples of suckling pups, which were processed by the neural network method. Data analysis of embryos (E13) obtained by the same method did not allow data analysis due to high...
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Impact of Probiotic Bacteria on Allergic Sensitization in Type I Allergy Model
Schwarzer, Martin ; Kozáková, Hana (advisor) ; Prokešová, Ludmila (referee) ; Nevoral, Jiří (referee)
The main goal in reversing the allergy epidemic is the development of effective prophylactic strategies. Early life events, such as exposures to microbes, have a major influence on the development of balanced immune responses. Due to their ability to interact with host immune system and to modulate host immune responses probiotics, mainly bifidobacteria and lactobacilli have been used with some success in prevention of allergic disease. In order to be referred to as probiotic, bacterial strain has to undergo rigorous testing. We have selected three new Lactobacillus (L.) strains out of 24 human isolates according to their antagonistic activity against pathogenic bacteria, resistance to low pH and milieu of bile salts. Safety of these strains was proven upon intragastric administration to mice; moreover, we have shown their ability to shift cytokine Th1 - Th2 balance towards non-allergic Th1 response in isolated splenic cells. Allergen specific prophylaxis using probiotics as vehicles for mucosal delivery of recombinant allergen is an attractive concept for development of well-tolerated and effective allergy vaccines. We have shown that neonatal mono-colonization of germ-free mice with the L. plantarum NCIMB8826 strain producing the major birch pollen allergen Bet v 1 attenuates the development of...
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Vliv variability stavby rezonančního dřeva na jeho akustické vlastnosti
Schwarzer, Martin
This work was the structure of resonant spruce wood devoted to. The tree-ring widths and summer wood measure were measured. By use of non - destructive methods their acoustic properties were measured - speed of sound, acoustic constant, logarithmic decrement of damping, acoustic wave resistance, wood - density and Young's modulus. Data were statistically analyzed and the wood structure coefficient of variation for each specimen was calculated. There were three different methodologies for verification of the wood structure variability effect formulated. Subsequently, it was found that it is possible to determine the effect on the acoustic properties of the wood macroscopic structure variability.
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Vliv rekombinantní bakterie Lactobacillus plantarum na vývoj pylové alergieL
Schwarzer, Martin ; Repa, A. ; Wiedermann, U. ; Hrnčíř, Tomáš ; Daniel, C. ; Pot, B. ; Štěpánková, Renata ; Hudcovic, Tomáš ; Tlaskalová, Helena ; Součková, Martina ; Kozáková, Hana
Germfree mice were monocolonized with recombinant Lactobacillus plantarum producing Bet v 1. Subsequently mice were sensitized by intraperitoneal injections to Bet v 1. We found out that monocolonization with recombinant L. plantarum reduced the level of specific Bet v 1 specific IgE antibody and stimulated production of INF-gamma in spleen cells supernatants. We conclude that monocolonization by recombinant L. plantarum shifts the immune response towards Th-1 direction and that it is a promising vaccine candidate against type I allergy
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