Dissertations / Theses on the topic 'Perforin'
To see the other types of publications on this topic, follow the link: Perforin.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Perforin.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Kägi, David. "The role of perforin protein in lymphocyte mediated cytotoxicity /." [S.l.] : [s.n.], 1993. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10050.
Full text
2
Uhl, Dieter. "Einfluss körperlicher Ausdauerbelastung auf Perforin und Granzyme-B-exprimierende Lymphozytenpopulationen." [S.l.] : [s.n.], 2002. http://www.freidok.uni-freiburg.de/volltexte/440.
Full text
3
Semple, Patricia Lynn. "The role of the cytolytic mediators, granulysin and perforin, in tuberculosis." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/12403.
Full textAbstract:
Includes bibliographical references (leaves 150-175).Includes abstract.
Protective immunity against mycobacterial infection requires an effective cytolytic response, in addition to an intact Type l (Th1) cytokine pathway. Natural killer (NK) cells and cytolytic T-cells (CTL) are essential components of protective immunity against tuberculosis (TB) and mediate granule-dependent killing of infected cells. Granulysin, an antimicrobial protein, and perforin, a pore-forming molecule, have been found to co-localise in the granules of these two cell types. Granulysin has been shown to be directly cytotoxic to extracellular Mycobacterium tuberculosis (M.tb) and, together with perforin, is cytolytic against intracellular mycobacteria. This project evaluated the role of these two cytolytic mediators in TB.
4
Haeryfar, Seyed Mohammad Mansour. "Antiestrogens modulate the perforin/granzyme pathway of natural killer cell-mediated cytolysis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0001/MQ45052.pdf.
Full text
5
Fraser, Stephanie A. "Regulation of Perforin-mediated lysis by two endogenous grandule proteins, Calreticulin and Chymase I /." abstract and full text PDF (UNR users only), 1999. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:9961145.
Full text
6
Cartwright, Adam. "Investigating the gasket function and perforin secretion of the natural killer cell immune synapse." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/24104.
Full textAbstract:
Natural Killer (NK) cells interact with other cells through a structured interface, the immune synapse (IS). A balance of signals controls NK cell activity through ligation of activating and inhibitory receptors. If signaling favours activation, NK cells mediate the directed secretion of cytotoxic mediators, such as perforin (PFN). To test whether the IS also functions as a gasket to extracellular molecules, fluorescently labeled nanometer-scale dextrans of varying sizes were co-incubated with effector-target cell-cell conjugates. Quantitative fluorescence microscopy of synapses revealed that dextrans with hydrodynamic diameters ≥32 nm were excluded from activating synapses, whilst smaller dextrans could enter. Size-dependent exclusion required an intact filamentous actin scaffold, but not continuous reorganisation following synapse formation. Time-lapse microscopy further revealed that the synapse assembles in a zipper-like manner, clearing larger dextran from the synapse. In addition, monoclonal antibodies and low-density lipoproteins were also excluded from the IS, whereas smaller domain antibodies could penetrate. NK cells can lyse more than one target in series. Whilst it is known that, among other proteins, PFN is secreted to lyse diseased cells, the amount of PFN secreted by NK cells is currently unknown. To quantify PFN release following stimulation through NKG2D or CD16, NK cells were plated on protein-coated surfaces that could capture PFN. Quantification using fluorescence microscopy revealed that PFN secretion was analogue, varying with increased ligand density. Simulating serial killing, repeated stimulation decreased the amount of PFN secreted with sequential activation. Unexpectedly, CD16 stimulation following serial NKG2D ligation recovered this decrease in secretion, however a similar recovery was not seen under reciprocal conditions. These data show that the activating IS clears and excludes extracellular molecules, including antibodies, in a size-dependent manner. Further, NK cell PFN secretion is an analogue response that varies with both ligand density and the receptors ligated in series.
7
Tinangon, Maria M. "Strategies to identify granzyme J /." abstract and full text PDF (UNR users only), 2001. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1404986.
Full text
8
Bradley, Michael Joseph. "Role of CD44, Fas Ligand, and Perforin in the Cytotoxicity Mediated by Natural Killer Cells." Thesis, Virginia Tech, 1997. http://hdl.handle.net/10919/36792.
Full textAbstract:
Two important mechanisms of lymphocyte-mediated cytotoxicity, one perforin based and the other Fas ligand (FasL) based, have been characterized recently. It has also been shown that CD44, an adhesion molecule, can participate in signaling cytotoxic activity of cytotoxic T lymphocytes (CTLs). In the current study we tested the hypothesis that activation of natural killer (NK) or lymphokine activated killer (LAK) cells induces the expression of FasL, perforin, and CD44 which together contribute towards increased cytolytic activity. To this effect, we used wild-type mice, perforin-knockout mice, and mice lacking a functional FasL. We observed that both interleukin-2 (IL-2) and Poly I:C triggered NK/LAK cells to lyse targets through the perforin- and FasL- pathways. In addition, Fas+ tumor targets were more susceptible to lysis by poly I:C and IL-2 activated NK/LAK cells when compared to Fas- targets. Furthermore, Fas- tumor cells injected subcutaneously into syngeneic mice could grow and induce tumors, whereas, Fas+ tumors were rejected. IL-2 treatment increased the CD44 expression on NK cells, which was responsible for the lysis of endothelial cells through its ligand, hyaluronate. Upregulation of perforin and FasL in activated NK/LAK cells may explain why such cells can kill a wide variety of tumor cells efficiently. On the other hand, activated NK/LAK cells express increase increased levels of CD44 and use this molecule to mediate cytotoxicity of endothelial cells, which may account for the vascular leak seen during IL-2 therapy.Master of Science
9
Rafatpanah, Baygi Houshang. "Immunogenetic analysis of patients with HTLV-I infection : associations with HLA, cytokine and perforin gene polymorphisms." Thesis, University of Manchester, 2003. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488453.
Full textAbstract:
Human T lymphotropic virus type (HTLV-I) is associated with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia (ATL). Fewer than 2% of HTLV-I-infected individuals develop HAM/TSP. The different outcome of HTLV-I infection may be explained by the existence of viral agents, genetic background or even environmental factors. In the initial part of this study we determined if there was a correlation between cytokine gene polymorphisms, mainly Thl and Th2, in Iranian patients with HAM/TSP, asymptomatic HTLV-I carriers and healthy controls. It was shown that polymorphisms in the TNF-alpha gene promoter at position -308, in TGF-beta1 gene at codons 10_and 25, in IL-10 at positions -1082, -819, -592, in IFN-gamma at position +874, in IL-13 at position +2043 and in IL-4 at position -590 correlates with differential production of these cytokines in vitro. There was a significant difference between HAM/TSP patients and healthy controls in the distribution of IL-10 promoter polymorphisms at position -819 and -592 (p=0.01) and HTLV-I carriers and healthy controls (p=0.02). The frequency of the IL-10 low producer haplotype (ATA) was significantly associated with HAM/TSP compared with healthy controls (p=0.01) and HTLV-I carriers with healthy controls (p=0.02). These data suggest that IL-10 -819 and -592 polymorphisms are associated with HTLV-I infection. However, how this influences HAM/TSP patients and HTLV-I carriers remain unknown. In contrast, we failed to detect any differences in the frequencies of other cytokines between any of the three groups. In this part, we also analysed the influence of HLA class II DRB1 alleles and class I HLA-A2, A-30, CW8 and B54 alleles in all three groups. The frequency of the HLA-DRB1*01 allele was significantly increased in HAM/TSP patients compared with carriers (p=0.03). In contrast, the distribution of HLA-DRB1*014 was higher in HTLV-I carriers compared to HAM/TSP patients (p=0.03). There was also a significant difference in the frequency of HLA-CW8 between HAM/TSP patients and healthy controls (p=0.01). HLA typing suggests that HLA-DRB1*01 and HLA-CW8 are relative risk factors for development to HAM/TSP, whereas possession of the HLA-DRB1*014 allele decreases the risk of HAM/TSP. In this case, the role of other genetic backgrounds should be taken into account. The second part of this study was to define GM-CSF polymorphisms and to seek association between GM-CSF polymorphism and HTLV-I infection. The 5'-flanking region, promoter, exon 1 and 2 and 3'UTR of GM-CSF was screened for detection of polymorphism by SSCP and sequencing. Three novel polymorphisms were found in the 5'-flanking region of GM-CSF at positions -677*A/C, -1440*A/G and -1916*T/C, relative to the translation start site. Mitogenic stimulation of PBMCs from healthy controls showed no correlation between GM-CSF gene polymorphisms and protein level. However, a gel shift assay demonstrated that the -611*A allele binds the transcriptional factor TEF-2 better than the -677*C allele. The frequencies of GM-CSF polymorphisms were the same in all of the HTLV-I groups and controls. In the third part of our study, we screened the promoter and first intron of the perforin gene, as a key factor in elimination of viral-infected cells, to determine novel polymorphisms. A novel polymorphism at position +418 relative to the transcription start site was detected. Results from flow cytometry and Western blotting in non stimulated and stimulated PBMCs showed no association between perforin gene polymorphism and perforin expression. The frequency of the +418*C allele in HAM/TSP patients was significantly increased compared with healthy controls (p=0.015). There was also a difference in the distribution of +418*C allele between HAM/TSP patients and HTLV-I carriers, but this did not reach significant levels (p=0.09). This result suggests that the +418*C allele acts as genetic risk factor for development of HAM/TSP.
10
Woodsworth, Daniel. "Characterizing the granzyme-perforin pathway and its utility as a cell-to-cell delivery system for cellular therapeutics." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62073.
Full textAbstract:
Alongside small molecules and biologics, cell-based therapies are emerging as a third class of medical therapy. Additional sensors, actuators and control circuits would greatly expand the range of function and application of cellular therapeutics. To this end, a cell-to-cell delivery module has been developed by investigating and re-engineering the granzyme-perforin pathway of cytotoxic lymphocytes. A computational biophysical model of this process was developed and implemented using a spatial stochastic simulation algorithm, which indicated that hindered diffusion in the immune synapse is critical to ensure reliable granzyme internalization and that large amounts of granzyme escape the synapse, but should not have toxic effects due to rapid spatiotemporal dilution. Additionally, these results indicated that passive diffusion is sufficient for granzyme entry into the target cell, which motivated efforts to use granzyme as a molecular chaperone to transfer exogenous payloads from effector to target cells. Using a fluorescent protein payload, the subcellular localization of several granzyme B derived chaperones was characterized using fluorescence microscopy, and then their capacity to transfer the payload to target cells was evaluated in co-culture experiments. The results indicated that the motifs in granzyme B that are required for lytic granule loading are only functional and contiguous in the folded protein. Additionally, these experiments demonstrated that full length granzyme B is a suitable chaperone for delivering protein payloads to target cells via the granzyme-perforin pathway. Attempts were then made to use this system to deliver potent orthogonal toxins to apoptosis and lymphocyte resistant tumor cells. A range of granzyme B toxin fusion proteins were constructed, all of which retained toxic activity to varying degrees. To render target cells resistant to lymphocyte attack both small molecule and protein based inhibitors of apoptosis were tested in several cell lines, which delayed cell death, but did not stop it. Using effector target dose response curves, a moderate increase in target cell death was observed in cells targeted by lymphocytes expressing granzyme toxin fusion proteins, as compared to wild type lymphocytes, but the biological significance of this effect is uncertain. Approaches to improve this granzyme-perforin mediated delivery system and its therapeutic utility are discussed and explored.Science, Faculty of
Graduate
11
Natarajan, Kshama. "Part I- cluster assembly in protein bound iron-sulfur clusters ; Part II- solution structural studies on the N-terminus perforin /." The Ohio State University, 1998. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487951907957761.
Full text
12
Khazen, Roxana. "Dissecting early mechanism of melanoma cell resistance to cytotoxic T lymphocyte attack." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30007/document.
Full textAbstract:
Les cellules de mélanome humain expriment différents antigènes tumoraux qui sont reconnus par les lymphocytes T cytotoxiques CD8 + (CTL) induisant des réponses spécifiques de la tumeur in vivo. Cependant, chez les patients atteints de mélanome l'efficacité de la réponse naturelle des CTL ou stimulée par thérapie est limitée. Les mécanismes sous-jacents de l'échec de la phase effectrice des CTL contre les mélanomes sont encore largement méconnus. Notre hypothèse est que l'efficacité limitée des CTL dans leur combat contre les tumeurs est le résultat d'une balance défavorable entre la capacité des CTL à tuer les tumeurs et une résistance tumorale intrinsèque à l'activité cytolytique des CTL. Au cours de ma thèse je me suis concentrée sur la dynamique moléculaire qui se produit à la synapse lytique afin de pouvoir identifier un mécanisme précoce mis en place par les cellules de mélanome face à l'attaque des CTL. En combinant l'utilisation d'approches de microscopie de pointe et des outils moléculaires, j'ai pu montrer que, lors de l'interaction avec les CTL, les cellules de mélanome humain subissent une activation de leur trafic vésiculaire endosomal et lysosomal, lequel est intensifié à la synapse lytique et corrèle avec la dégradation par la cathepsine de la perforine et un défaut de pénétration d'entrée du granzyme B. De plus, j'ai démontré que le blocage du trafic lysosomal dépendant de SNAP23, la modification du pH (intra-vésiculaire) et l'inhibition de l'activité lysosomale protéotlytique des cellules de mélanome permet de restaurer leur sensibilité à l'attaque des CTL. Nos résultats révèlent une stratégie sans précédent d' " auto-défense " des cellules de mélanome à la synapse immunologique basée sur une sécrétion lysosomale massive et sur la dégradation de la perforine sécrétée par les CTL. Ainsi pouvoir interférer avec cette stratégie synaptique d'auto-défense des cellules de mélanome pourrait contribuer à potentialiser les réponses des CTL et les immunothérapies chez les patients atteints de mélanomeHuman melanoma cells express various tumor antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL) and elicit tumor-specific responses in vivo. However, natural and therapeutically enhanced CTL responses in melanoma patients are of limited efficacy. The mechanisms underlying the failure of CTL effector phase against melanomas are still largely elusive. Our hypothesis is that the limited efficacy of CTL in their fight against tumors is the result of an unfavorable balance between CTL ability to kill tumors and an intrinsic tumor resistance to CTL cytolytic activity. During my thesis I focused on the molecular dynamics occurring at the lytic synapse in order to identify possible "early response-mechanism" of melanoma cells to CTL attack. Using a combination of cutting edge microscopy approaches and molecular tools, I showed that upon conjugation with CTL, human melanoma cells undergo an exacerbated late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration. Abortion of SNAP-23-dependent lysosomal trafficking, pH perturbation or impairment of lysosomal proteolytic activity restores susceptibility to CTL attack. Our results reveal an unprecedented strategy of melanoma cell "self-defense" at the immunologic synapse based on a lysosome secretory burst and perforin degradation at the lytic synapse. Interfering with this synaptic self-defense strategy might be instrumental to potentiate CTL-mediated therapies in melanoma patients
13
Chang, Eddie. "The role of perforin and chemokines in the pathogenesis of chronic corneal inflammation induced by herpes simplex virus type-1 infection." free to MU Campus, others may purchase, 2003. http://wwwlib.umi.com/cr/mo/fullcit?p3091911.
Full text
14
Lage, Denise 1979. "Doenças liquenoides da pele e mucosa oral = análise histológica e imuno-histoquímica = Lichenoid diseases of the skin and oral mucosa : histological and immunohistochemical analysis." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312892.
Full textAbstract:
Orientador: Maria Letícia CintraTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-24T06:34:44Z (GMT). No. of bitstreams: 1 Lage_Denise_D.pdf: 12121159 bytes, checksum: f93ebe72b9dc8acf40f7ff2245de6a21 (MD5) Previous issue date: 2014
Resumo: O líquen plano (LP) pode afetar a pele e/ou as mucosas. Histologicamente apresenta infiltrado linfo-histiocitário na junção epitélio-tecido conjuntivo e apoptose de células epiteliais basais. No LP oral (LPO), ocorre erosão frequente pela maior intensidade da necrose. O LP cutâneo (LPC) e o LPO apresentam características histopatológicas similares, mas o curso clínico é diverso. O LPC costuma ter seu curso limitado, enquanto o LPO é frequentemente recidivante. A erupção liquenoide a droga (ELD) desenvolve-se após semanas da ingestão do medicamento e a resolução do quadro é lenta após a interrupção, dificultando o diagnóstico diferencial com o LP idiopático. Os achados clínicos e histológicos podem ser indistinguíveis daqueles do LP, mas a patogênese da ELD não é conhecida. Diferenças locais no sistema imune da mucosa oral e pele poderiam explicar a diversidade no comportamento clínico do LP. Quanto à ELD, há poucas publicações sobre as alterações imunes que atuam no seu desenvolvimento. A citotoxidade celular é mediada, dentre outros mecanismos, por grânulos contendo granzima B e perforina, produzidos por linfócitos T citotóxicos e células natural killers. Com o objetivo de estudar a citotoxicidade celular na patogênese destas doenças, foram analisadas 29 amostras de LPO, 16 de LPC e 6 de ELD. Os cortes foram corados pela H&E e técnica de imuno-histoquímica, para a demonstração de linfócitos CD4 e CD8, macrófagos HAM 56+ e MAC 387+, granzima B, perforina e ICAM-1. As amostras de LPO apresentaram maior densidade de células granzima B+ e perforina+, em comparação às do LPC. Nos dois grupos de doenças, quanto maior era o número de células perforina+, maior era o de células granzima B+. Maior número de células CD4-positivas foi encontrado nas lesões ativas, quando comparado com o das regressivas, no LPO, mas não no LPC. À comparação entre o LPC e a ELD, quanto maior o número de células CD8-positivas, maior era o número de células que expressavam a perforina no grupo LPC. Quanto maiores eram os valores da granzima B, maiores os da perforina, no grupo LPC. Quanto maiores eram os valores da granzima B, maiores os de células apoptóticas agregadas, no grupo da ELD. Nas amostras do LPC, quanto maiores os valores das células T, maiores os dos macrófagos HAM56-positivos e vice-versa. Nas amostras da ELD, foi encontrada correlação negativa entre o número de células T e o de histiocitos jovens (MAC 387+). Havia correlação positiva entre o número de células T e o de células CD8, no grupo da ELD. O mesmo não ocorreu, no grupo do LPC. Concluindo, a expressão aumentada dos grânulos citotóxicos no LPO pode estar associada à maior gravidade da doença na mucosa. Os resultados favorecem um papel mais importante da granzima B e linfócitos TCD8+, no mecanismo patogenético da ELD, comparativamente com o da perforina, de maior importância no LPC. É possível que a ação da granzima B esteja ligada ao número abundante de clusters encontrado na ELD. Embora o LPC e a ELD apresentem semelhanças clínicas e histológicas, a etiopatogênese parece ser distinta
Abstract: Lichen planus (LP) can affect the skin and/or mucous membranes. Histologically it presents lymphohistiocytic infiltrate in the epithelium-connective tissue junction and apoptosis of basal epithelial cells. In oral LP (OLP), erosion occurs frequently by higher intensity of necrosis. Cutaneous LP (CLP) and OLP present similar histopathological features, but the clinical course is diverse. Spontaneous remission is common in CLP, but OLP follows a prolonged course, with periods of remission and relapse. Lichenoid drug eruption (LDE) develops after weeks of drug intake and the resolution of lesions is slow after drug discontinuation, hampering the differential diagnosis with (idiopathic) LP. Clinical and histological findings of LDE may be indistinguishable from those of LP, but LDE pathogenesis is poorly understood Local differences in the immune system of the skin and oral mucosa could explain the diversity in the clinical behavior of CLP and OLP. Regarding LDE, there are few publications on the immune changes that act in its development. Cellular cytotoxicity is mediated, among other mechanisms, by granules containing perforin and granzyme B, produced by cytotoxic T lymphocytes and NK cells. In order to study cellular cytotoxicity in the pathogenesis of these diseases, we analyzed 29 samples of OLP, 16 of CLP and 6 of LDE. The sections were stained for H&E and immunohistochemically targeted with CD4, CD8, HAM 56, MAC387, granzyme B, perforin and ICAM-1. OLP specimens exhibited higher density of cytotoxic granules (perforin and granzyme B) when compared with CLP. In both groups of diseases, the greater the number of perforin+ cells, the greater was the number of granzyme B+ cells. Increased number of CD4+ cells was found in active lesions as compared with the regressive ones in OLP but not in the CLP. The comparison between CLP and LDE revealed that the greater the number of CD8+ cells, the greater the number of cells expressing perforin in CLP group. The higher were the values of granzyme B, the higher the perforin values in the CLP group; the higher were the values of granzyme B, the higher the number of clusters of apoptotic cells in the LDE group. Within CLP group, the higher were the values of T cells, the greater the number of HAM56+ macrophages and vice versa. In LDE samples, negative correlation was found between the number of T cells and young histiocytes (MAC 387+). There was a positive correlation between the number of T cells and CD8 cells in LDE group, but not in CLP group. Concluding, increased expression of cytotoxic granules in OLP may be associated with greater mucosa severity. The results favor a greater role of granzyme B and CD8+ lymphocytes in the pathogenic mechanism of LDE, when compared with perforin, of greater importance in CLP. It is possible that the action of granzyme B is connected to the abundant number of clusters found in LDE. Although CLP and LDE present clinical and histological similarities, the etiopathogenesis appears to be distinct
Doutorado
Anatomia Patologica
Doutora em Ciências Médicas
15
Camiña, Tato Montserrat. "Estudio del papel de los genes perforin 1 (PRF1), caspase 8 (CASP8) y B-cell translocation gene 1 (BTG1) en esclerosis múltiple." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/399348.
Full textAbstract:
El estudio de las bases genéticas de las enfermedades es clave para un diagnóstico mejor y más rápido de las patologías así como, para su mejor tratamiento. En los últimos años se han descubierto un gran número de genes que pueden generar susceptibilidad a la EM, sin embargo, hay muchos que aún están pendientes de replicación en otras poblaciones.
El objetivo principal de esta tesis es la confirmación de la participación en la susceptibilidad a padecer EM de tres genes. En concreto se trata de los genes PRF1, CASP8 y BTG1.
Tras realizar genotipado de SNPs por discriminación alélica y estudios de expresión mediante microarrays, entre otras técnicas, se han obtenido resultados que apuntan a que los tres genes podrían participar de forma moderada en la susceptibilidad a padecer EM.
En el caso del gen PRF1 se observa una fuerte asociación entre éste y la susceptibilidad a padecer la enfermedad, sobre todo en hombres con formas de EMPP.
Los resultados para el gen CASP8 muestran asociación entre este gen y la susceptibilidad a padecer la enfermedad en formas de EMPP. También se observa una asociación entre CASP8 y la progresión del curso de la enfermedad.
Por último, los resultados para el gen BTG1 muestran también asociación entre este gen y la susceptibilidad a padecer la enfermedad en formas de EMRR/SP.The study of the genetic basis of the diseases is key not only for a better and fast diagnostic of the diseases, but also for a better treatment. In recent years, many genes that confer susceptibility to MS have been discovered; however, many remain yet to be replicated in other populations. The main objective of this doctoral thesis is to confirm the involvement of the following genes in the susceptibility to MS: PRF1, CASP8 and BTG1. After performing SNP genotyping by allelic discrimination and expression studies by microarrays, among other studies, our results indicate that the three genes may contribute in a modest way to the susceptibility to MS. In the case of the PRF1 gene, we observed a strong association between this gene and the susceptibility to MS, mainly in males with PPMS forms. The results with the CASP8 gene suggest an association between this gene and the susceptibility to MS in patients with PPMS. In addition, we observed an association between the CASP8 gene and the course of MS. Finally, the results with the BTG1 gene suggest an association between this gene and the susceptibility to suffer MS in forms with relapse-onset course.
16
Mossu, Adrien. "Régulation de la survie des cellules dendritiques plasmacytoïdes dans un contexte inflammatoire non viral." Thesis, Besançon, 2015. http://www.theses.fr/2015BESA3011/document.
Full textAbstract:
Les cellules dendritiques plasmacytoïdes (pDC) sont spécialisées dans la lutte antivirale, notamment grâce à leur capacité à sécréter des IFN de type I. Néanmoins, elles sont aussi impliquées dans Pactivation des réponses immunitaires adaptatives, et des lymphocytes T (LT) en particulier. C'est pourquoi, lors d'épisodes inflammatoires chroniques ou incontrôlés, les pDC sont à l'origine de l'initiation ou du maintien de syndromes inflammatoires et du développement de pathologies auto-immunes. Il doit donc exister des mécanismes permettant de contrôler l'activité de ces cellules. À l'aide d'un modèle in vivo d'inflammation non virale induite par l'injection d'un anticorps anti-CD3 (Ac aCD3), nous avons observé une apoptose des pDC dans différents organes lymphoïdes, et ce de façon dépendante de l'activation des lymphocytes T. De plus, nous avons pu observer que la diminution de la survie des pDC dans ce contexte inflammatoire n'était pas associée à l'orage cytokinique induit par l'efièt mitogénique de l'Ac aCD3. En revanche nos résultats montrent que les LT CD8* et la voie cytotoxique de la perforine dans ce contexte inflammatoire aigu sont responsables de la déplétion des pDC. Nous avons également étendu ces résultats à d'autres situations inflammatoires stériles comme lors de la maladie du greffon contre l'hôte. Ces données suggèrent que cette voie de régulation pourrait être utilisée à des fins thérapeutiques, afin de contrôler la survie des pDC impliquées dans la physiopathologie de syndromes auto-immuns comme le lupus érythémateux disséminé, le psoriasis, la sclérose en plaques ou encore le diabète de type IPlasmacytoid dendritic cells (pDC) are specialized in type I interferons (IFN-I) secretion to control viral infections. However, these cells can also activate adaptive immune responses, and polarize T cells. Indeed, during chronic or uncontrolled inflammatory episodes, pDC can induce or maintain inflammatory syndromes and autoimmune diseases. So some mechanisms should exist to control the fonction of these cells. In an in vivo modcl of non viral inflammation induced by the injection a CD3-specific antibody (aCD3 Ab), we could observed pDC's apoptosis dependent of T cell activation in different lymphoid organs. Moreover, we could observe that this depletion of pDC was not associated with the cytokinic storm induced by the mitogenic effect after aCD3 Ab treatment. On the other hand our data shovved that CD8+ T cells and the perforin pathway in this acute inflammatory context are responsible for pDC depletion We also obtained the same results in other non viral inflammation settings such as graft versus host disease. Overall, these data suggesi that this regulation pathway could be used for therapeutic purposes, to control pDC survival and avoid their involvement in the physiopathology of autoimmune disorders like systemic lupus erythematosus, psoriasis, multiple sclerosis or type I diabetes
17
Novais, Fernanda Oliveira. "Avaliação do papel das células T CD8+ na infecção experimental por Leishmania braziliensis." reponame:Repositório Institucional da FIOCRUZ, 2011. https://www.arca.fiocruz.br/handle/icict/4200.
Full textAbstract:
Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-18T21:46:22Z
No. of bitstreams: 1
Fernanda Oliveira Novais Avaliacao do papel....pdf: 2271339 bytes, checksum: eee5aa084065678cf55651296f356919 (MD5)Made available in DSpace on 2012-07-18T21:46:22Z (GMT). No. of bitstreams: 1 Fernanda Oliveira Novais Avaliacao do papel....pdf: 2271339 bytes, checksum: eee5aa084065678cf55651296f356919 (MD5) Previous issue date: 2011
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil
Linfócitos T CD8+ são células do sistema imune adaptativo capazes de induzir a morte de células infectadas através de mecanismos citotóxicos. No modelo de infecção intradérmica por Leishmania revelou-se que os linfócitos T CD8+ são responsáveis tanto pela indução de patogênese bem como pela imunidade contra a infecção primária por L. major. Até o momento, o papel dos linfócitos T CD8+ não foi estudado na infecção experimental por L. braziliensis. Neste estudo, investigamos o recrutamento dos linfócitos T CD8+ para o sítio de infecção e determinamos a sua função. Cinco semanas após a infecção intradérmica por L. braziliensis, camundongos BALB/c apresentaram um aumento na porcentagem de linfócitos T CD8+ presentes na orelha infectada e estes produziram, principalmente, IFN-g e Granzima B. Já no linfonodo de drenagem, estas células não produzem granzima mas, sim, IFN-g e TNF-a. Utilizando o mesmo modelo de infecção, camundongos BALB/c ou C57BL/6 depletados de linfócitos T CD8+ ou camundongos deficientes em b2-microglobulina ou em CD8 apresentaram redução no tamanho da lesão ao longo da infecção e menor carga parasitária cinco semanas após a infecção. A depleção de linfócitos T CD8+ não induziu qualquer alteração no recrutamento e produção de IFN-g, TNF-a e IL-10 pelos linfócitos T CD4+ no sítio de infecção ou no linfonodo de drenagem. Além disso, a capacidade proliferativa ou a produção de citocinas específicas in vitro após estímulo com células dendríticas infectadas por L. braziliensis não sofreram alteração. A ausência de linfócitos T CD8+ após a 8 infecção por L. braziliensis também não alterou o recrutamento de monócitos inflamatórios nem a sua diferenciação em células dendríticas. Por último, a análise histológica e de citometria de fluxo mostrou aumento no recrutamento de neutrófilos para o sítio de infecção e este resultado pode ser correlacionado com o controle da doença. Para confirmar o envolvimento dos linfócitos T CD8+ no desenvolvimento de lesão por L. braziliensis, transferimos linfócitos T CD8+ de camundongos naïve ou imunes, bem como linfócitos T CD4+ somente ou linfócitos T CD8+ e T CD4+ para camundongos RAG-/-. Neste contexto, a transferência de linfócitos T CD8+ naïve ou imunes induziu uma intensa patologia no sítio de infecção bem como a disseminação de parasitas para outros sítios, como a orelha não infectada, pata e nariz. Camundongos RAG-/- controle e aqueles que receberam linfócitos T CD8+ naïve ou imunes apresentam a mesma quantidade de parasitas no sítio de infecção, embora o aspecto da lesão tenha sido muito diferente. A transferência de linfócitos T CD4+ foi capaz de controlar a carga parasitária nestes animais e o mesmo foi observado após transferência de linfócitos T CD4+ e T CD8+ em conjunto. Nestes animais não observamos lesões em outros sítios, indicando que os linfócitos T CD8+ contribuem para a disseminação dos parasitas. Por último, transferimos linfócitos T CD8+ provenientes de camundongos selvagens ou deficientes de IFN-g e perforina e observamos que, na ausência de perforina, a patologia e a disseminação parasitária são controladas. Portanto, este estudo sugere envolvimento dos linfócitos T CD8+ na patogênese induzida por L. braziliensis devido ao seu potencial citotóxico e, em paralelo, inibindo o recrutamento de neutrófilos para o sítio de infecção.
CD8+ T lymphocytes are part of the adaptive immune system and are considered cytotoxic because of their ability to induce death in infected cells. Using the intradermal model of Leishmania infection, it has been shown that CD8+ T cells play an essential role in both pathogenesis and immunity to primary infection with L. major in the skin. So far, the role of these lymphocytes in the experimental model of infection using L. braziliensis has not been evaluated. In this study we determined the recruitment and function of these cells upon infection with L. braziliensis. Five weeks after infection, the frequency of CD8+ T cells was increased in the dermal site and these cells produced mainly IFN-g and granzyme B in infected mice. In the draining lymph nodes, these cells produced high levels of IFN-g and TNF-a, but not granzyme B. Using the same intradermal model of infection, we analysed the outcome of infection in the absence of CD8+ T lymphocytes using both antibody depletion in BALB/c and C57BL/6 mice and mice deficient in b2- microglobulin and CD8. In all groups, the absence of CD8+ T cells was correlated with better control of lesion development and parasite load in both depleted BALB/c and in b2-microglobulin deficient mice. In the absence of CD8+ T cells, CD4+ T lymphocytes were recruited to the same extension and produced same levels of IFN-g, TNF-a and IL-10 both in the infected ear and in draining lymph nodes when compared to infected mice that were not depleted. Also, there was no change in the proliferative potential and in IFN-g production by these cells after re-stimulation with infected dendritic cells. Analysis of inflammatory monocyte recruitment and differentiation of these cells into dendritic cells were similar in both depleted and non-depleted mice. On the other hand, histological and flow cytometric analyses showed increased neutrophil recruitment to the site of infection and this can be correlated with disease control. To confirm the role of CD8+ T cells in the lesion development of L. braziliensis infected mice, we then transferred CD8+ T cells from naïve or immune mice, as well as CD4+ T cells alone or together with T CD8+ to RAG deficient mice. The transfer of CD8+ T cells from immune or naïve mice into RAG recipients induced an intense pathology upon infection with L. braziliensis in the infection site, but also in uninfected tissues such as the uninfected ear, nose and footpad. Evaluation of parasite numbers in the infected ear showed that RAG deficient mice without T cells and those transferred with CD8+ T cells from naïve or immune mice had similar number of parasites although the pathology was very different. The transfer of CD4+ T cells alone or in association with CD8+ T cells induced parasite control in the infection site. In these mice, we could not detect lesions in other sites and we concluded that the transfer of CD8+ T cells alone induces parasite dissemination in RAG deficient mice. Finally, the transfer of CD8+ T cells from perforin deficient mice led to control in lesion development and in parasite dissemination. In this study we can conclude that CD8+ T cells are involved in the pathogenesis of L. braziliensis due to their cytotoxic potential and by inhibiting neutrophil recruitment to the infection site.
18
Herrmann, Alexander Michael [Verfasser], and Heinz [Gutachter] Wiendl. "CD8+ Lymphozyten mediierter Angriff auf Neuronen des ZNS: Relevanz von Granzym B und Perforin für akute elektrophysiologische Veränderungen / Alexander Michael Herrmann. Gutachter: Heinz Wiendl." Würzburg : Universität Würzburg, 2015. http://d-nb.info/1108781152/34.
Full text
19
Sumaria, Nital. "The relevance of specific molecular and cellular effectors during murine cytomegalovirus infection." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0116.
Full textAbstract:
[Truncated abstract] The design and development of effective anti-viral immunotherapies requires a comprehensive understanding of the cellular and molecular processes that are involved in the generation and regulation of immune responses. The fundamental objective of the immune system is to successfully complete the task of eliminating/controlling the invading pathogen without causing overt pathology. Cytomegaloviruses (CMVs) are large DNA viruses that are able to evade immune attack and persist lifelong within the host. In a healthy host, CMV causes an asymptomatic infection, but in instances of decreased immune functions, such as in newborns, acquired immunodeficiency syndrome (AIDS) patients and transplant recipients, the infection can result in serious morbidity and mortality. Thus, human CMV (HCMV) is a clinically important pathogen and an understanding of the pathogenesis, mechanisms of immune subversion and, importantly the cascade of immune events that ensue following infection is highly relevant. The studies presented in this thesis have provided useful insight into various aspects of viral immunity and it is hoped that they will assist in the design of more effective therapies against viruses of clinical importance. Genetic variability in humans can greatly influence anti-viral immune responses and the outcome of viral infection. ... Furthermore, these studies provide novel evidence that NK cells are also crucial for the control of virus in some organs of susceptible mice during early acute infection. The data reveals that both NK cells and CD8+ T cells utilise perforin- and IFN-? dependent control of MCMV. Furthermore, these studies provide novel evidence that protection mediated by Ly49H+ NK cells in resistant mice is dependent on perforin. Chapter 3 focuses on the biological relevance of Grz during MCMV infection. These studies found that GrzA and GrzB are essential components of the machinery involved in limiting MCMV during acute infection. These analyses also provide the first evidence suggesting that GrzM plays a role, albeit minor, in controlling MCMV replication. Furthermore, the current studies suggest that Grz can mediate direct antiviral activities independent of the induction of cell death in conjunction with perforin. Interestingly, in the absence of both GrzA and GrzB (GrzAB), mice were as susceptible to MCMV infection as perforin-deficient mice. However, unlike perforin-deficient mice, GrzAB-deficient mice controlled and survived the infection. In Chapter 4 the roles of perforin, GrzA and GrzB in anti-viral immunity and immunopathology during MCMV infection were examined. These studies show that NK cell-derived perforin is required to eliminate infected targets as well as activated effector cells, suggesting that NK cells are crucial not only in defensive immunity but also in limiting the immune activation that follows MCMV infection. In summary, the studies presented in this thesis define the significant role played by specific effector molecules in limiting MCMV replication during different stages of this viral infection. Furthermore, these studies provide novel evidence that perforin, GrzA and GrzB play distinct roles in defensive immunity and limiting immunopathology during MCMV infection.
20
Musembi, Susan Mbithe. "Immunological assays relevant to definition of bovine theileria parva-specific cytotoxic CD8+ T cell responses." Thesis, Brunel University, 2012. http://bura.brunel.ac.uk/handle/2438/7171.
Full textAbstract:
A major objective in Theileria parva subunit vaccine development is to induce a vaccine antigen specific response mediated by cytotoxic CD8+ T cells (CTL). Therefore it is essential to be able to measure the frequency of the responding CD8+ T cells after vaccination and correlate it with a clinical outcome on challenge. Recently concluded immunogenicity and efficacy studies of T. parva specific CTL antigens showed successful induction of CTL responses in some animals, which correlated with reduced disease severity after challenge. To provide correlates of immunity antigen-specific CD8+ T cell mediated IFN-γ responses and CTL lytic responses were measured over the course of the experiments. Several challenges presented in these trials aimed at optimising vaccine efficacy. While the IFN-γ ELISPOT is a sensitive and reliable assay widely used in vaccine research, the use of chromium/indium release assay remains to be the only assay in use that measures T. parva-specific CTL activity. Hence the overall goal of the study was to develop novel reagents and novel assays to identify parasite-specific CD8+ T lymphocytes with lytic potential. To address this objective, bovine perforin, granzymes A and B, as specific effector proteins expressed in activated CTL were cloned and expressed using a baculovirus expression system. Sequence analysis of the cloned cDNAs showed the isolated cDNA belonged to the perforin and granzyme sub-families respectively. Perforin cDNA demonstrated 85% homology to human perforin with presence of conserved regions resembling calcium binding motif, membrane attack complex component as well complement protein. The sequences encoded by the cloned granzyme A and B cDNAs have the features of a trypsin like serine protease and demonstrates over 70% homology to the human cDNA over the active enzyme region as well catalytic residues characteristic of serine proteases. The expressed polypeptides of all three proteins were used to produce specific antibodies for use as reagents in immunoassays including ELISpot and intracellular staining for flow cytometric analysis. While the antibodies showed reactivity to the recombinant proteins, these reagents displayed different functionality in the recognition of the native protein. Peptide-major histocompatibility complexes (MHC) class I tetrameric complexes (tetramers) are proving invaluable as fluorescent reagents for enumeration, characterisation and isolation of peptide-specific CD8+ T cells and have afforded advantages to phenotype antigen-specific T cells with minimal in vitro manipulation. Fluorescent bovine tetramers were shown to specifically stain antigen-specific CTL by directly binding the T cell receptor (TCR). Analyses of CD8 T-cell responses in live-vaccine immunised cattle also showed that this method is robust and demonstrates changes in the kinetics and specificity of the CD8+ T cell response in primary and secondary infections with T. parva. On average, results of functional assays and tetramer staining followed parallel trends, measured roughly the same populations and allowed for surface and intracellular staining for CD8 T cell marker and perforin, respectively, demonstrating a method that reliably quantifies the frequency, phenotype and function of specific CD8+ T cells. The technical simplicity, rapidity and ability of the flow cytometric technique described in this thesis to measure low frequency antigen-specific responses suggests that tetramer staining, combined with functional assays could be broadly applicable to the valuation of vaccination efficacy to determine which protocols are most successful in inducing CTL responses.
21
Augustin, M. (Merja). "Cytotoxic lymphocytes in children's cow's milk sensitive enteropathy of delayed type." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514277244.
Full textAbstract:
Abstract
Food hypersensitivities are becoming increasingly common worldwide. Previous studies indicate that cell mediated immunity has a role in delayed paediatric gastrointestinal food hypersensitivities, but the exact pathogenetic mechanisms are unknown. Cytotoxic activation of T-lymphocytes is known to play an important role in the pathogenesis of celiac disease (CD). The pathogenetic mechanisms of cow's milk protein sensitive enteropathy (CMSE) are largely unknown. CMSE is a non-IgE related type of food hypersensitivity with variable gastrointestinal symptoms but no visible mucosal abnormalities on light microscopy. The diagnosis is based on an open or blinded elimination/challenge test, as the endoscopic, histological and laboratory findings are generally non-specific.
This thesis aims to characterize the role of lymphocyte cytotoxicity in the pathogenesis and diagnosis of CMSE in preschool and school aged children, including comparison with CD where the pathogenetic significance of cytotoxicity is well established. The study cohort consisted of 151 children, including 57 with untreated CMSE, 18 with treated CMSE, 24 with CD, and 52 controls. Using immunohistochemistry, the mucosal expressions of cytotoxic T cell-restricted intracellular antigen type 1 (TIA-1), perforin, granzyme A and B were analysed in the duodenal bulb and descending duodenum. Intraepithelial T-lymphocytes were labelled with CD3, alpha/beta and gamma/delta T cell receptor antigens. To determine the rates of overall and epithelial apoptosis as well as proliferation, the immunohistochemical TUNEL technique, M30 and Ki-67 antibodies were used. Serum levels of granzymes, CD30 and soluble Fas were studied using ELISA method.
The number of intraepithelial lymphocytes with TIA-1, perforin and granzyme A containing granules was increased in CMSE. This increase was related to antigen challenge and not a constitutional abnormality. The cytotoxic reaction in CMSE differed from that in CD by being of lesser magnitude, concerning predominantly the descending duodenum and not showing signs of cytotoxicity related epithelial destruction. The serum levels of GrA, GrB and CD30 were increased in both CMSE and CD, correlating with the number of duodenal CD3+, alpha/beta and gamma/delta+ intraepithelial lymphocytes.
The results strongly support the role of cell-mediated immunity in the pathogenesis of CMSE. Mucosal cytotoxic activation seems to be manifested by the release of cytoxicity related proteins in serum. This provides a new approach to the monitoring of intestinal immune activation which could help in diagnosis and in objectively monitored treatment response.
22
Masouris, Ilias [Verfasser], and Elfriede [Akademischer Betreuer] Nößner. "Verteilung und zytotoxische Qualität von T-Zellen und natürlichen Killerzellen im klarzelligen Nierenzellkarzinom : Gefäßsystem-bezogene Lokalisation und Ausstattung mit Perforin beeinflussen Metastasierung und Tumor-spezifisches Überleben / Ilias Masouris. Betreuer: Elfriede Nößner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1084582740/34.
Full text
23
Fauteux-Daniel, Sébastien. "Étude du rôle de l’inflammasome et de la kinase Styk1 dans la régulation des lymphocytes cytotoxiques." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1052/document.
Full textAbstract:
Le dysfonctionnement de l'exocytose des granules cytotoxiques est responsable d'une susceptibilité accrue aux pathogènes intracellulaires qui s'accompagne de l'activation continue et anarchique des lymphocytes cytotoxiques et des macrophages. Ce phénomène conduit à la lymphohistiocytose hémophagocytique (HLH), un syndrome auto-inflammatoire fatal en absence d'intervention thérapeutique. Les mutations des gènes codant pour la perforine (PRF-1) ou pour certaines des protéines impliquées dans la biogénèse ou le transport vésiculaire des granules cytotoxiques sont causales des formes familiales ou primaires de la HLH (FHL). La HLH fait également partie des complications secondaires aux infections à herpesviridae et à certains désordres immunologiques importants tels que l'arthrite juvénile idiopathique (SoJIA). Au moment d'entreprendre les travaux présentés dans ce manuscrit, le premier cas de HLH induite par une mutation menant à l'activation constitutive de la composante NLRC4 de l'inflammasome était décrit. L'inflammasome est une structure multimérique composée d'un récepteur cytosolique, de la protéine échafaud ASC et de la Caspase-1. Son activation mène à la maturation des pro-formes de l'IL-1β et l'IL-18 ainsi qu'à leur sécrétion. L'activation constitutive de NLRC4 étant suffisante au déclenchement de la HLH, nous avons tenté de comprendre si cette structure y était essentielle dans le cadre des défauts génétiques de cytotoxicité. Nous avons donc invalidé la protéine ASC ou Caspase-1 dans le modèle murin de HLH déficient pour la perforine (PRF1 -/-). Nous avons également testé l'hypothèse qu'un déficit de cytotoxicité pouvait expliquer le développement de la HLH chez les patients souffrant de SoJIA. Nos résultats montrent que l'inflammasome est nécessaire à la production d'IL-18 lors de la HLH mais qu'il n'est pas essentiel au développement de la maladie dans le cadre des FHL. Par ailleurs, nous montrons que la cytotoxicité des cellules NK semble normale chez les patients atteints de SoJIA, ce qui suggère que les mécanismes immunologiques à l'origine de la HLH dans les FHL et dans les maladies autoinflammatoires comme la SoJIA sont distincts. Dans la seconde partie de ce manuscrit, nous avons étudié sur le rôle de la sérine/thréonine/tyrosine kinase Styk1 dans la régulation des lymphocytes cytotoxiques NK. Ces derniers sont responsables du contrôle immunitaire précoce des pathogènes intracellulaires et contribuent à l'immunosurveillance des cellules tumorales. Suite à leur activation, ils relâchent de très grandes quantités d'IFN-y et de TNF-α, faisant ainsi le lien entre l'immunité innée et adaptative. La reconnaissance des cellules cibles par les lymphocytes NK est gouvernée par l'expression d'un éventail de récepteurs qui transduisent des signaux, activateurs ou inhibiteurs, et dont la balance se traduit par l'activation ou la tolérance. Ces récepteurs sont codés au sein de deux complexes génétiques très denses, le complexe de cytotoxicité naturelle (NCR) et le complexe des récepteurs des leucocytes (LRC). Au moment de commencer ces travaux, nous avions révélé que l'expression de la kinase Styk1 fait partie de la signature transcriptionnelle des lymphocytes NK. Sa fonction dans le système immunitaire demeure toutefois inconnue. Néanmoins, la localisation génétique favorable de Styk1, près du NCR, ainsi que son implication dans la voie PI3K-AKT, en faisaient un candidat potentiel de régulation des lymphocytes NK. Afin de connaître le rôle de Styk1 dans le développement et les fonctions effectrices des lymphocytes NK, nous avons donc généré une souris pour laquelle Styk1 est invalidé. Nos résultats confirment que Styk1 est exprimée de façon spécifique par les cellules NK. Nous avons également détecté une diminution de l'activité constitutive de la voie AKT/mTOR dans les cellules NK, mais le développement, l'homéostasie et la fonction des cellules NK sont cependant normaux dans les souris déficientes en Styk1Upon recognition of infected or target cells, CD8+ T and Natural Killer (NK) lymphocytes initiate a polarized degranulation of vesicle storing cytotoxic molecules (perforin: PRF1 and granzyme B). By altering the target cell’s cellular membrane integrity, perforine allows granzyme B to translocate to its cytosol. Genetic anomalies may affect normal cytotoxic functions and severely hamper the control of intracellular pathogens. In this context, the pathogenic signal remains uninterrupted and both cytotoxic lymphocytes and macrophages are continuously stimulated. This auto-inflammatory pathological condition is named hemophagocytic lymphohistiocytosis (HLH) and is fatal without therapeutic intervention. HLH can also occur secondary to infection with viruses from the herpesviridae family, or be concomitant to important immune alterations such as systemic onset juvenile idiopathic arthritis (SoJIA), with no clear etiological cause identified. In 2014, a case of HLH mediated by the constitutive activation of the NLRC4 inflammasome receptor was first described. The inflammasome is a multimeric structure involving a cytosolic receptor, a scaffold protein – ASC – and Caspase-1. In the immune system, the inflammasome is expressed in macrophages and dendritic cells and senses pathogenic (PAMP) and danger (DAMP) associated signals. Once activated, inflammasome’s protein Caspase-1 catalyzes the maturation of pro-IL-1b and pro-IL-18 and leads to their secretion. Since NLRC4 constitutive activation appears to be sufficient for triggering HLH, we aimed to understand if the inflammasome structure was essential to the development of the syndrome. In order to address this question, we invalidated the inflammasome through the abrogation of ASC or Caspase-1 in PRF1 -/- HLH mouse model. We also tested the hypothesis that an altered cytotoxic function could explain the high prevalence of HLH in the proinflammatory context of SoJIA. The results we present here show that the inflammasome is responsible for the elevated levels of IL-18 in the serum of HLH patients. However, the inflammasome is facultative for its development. We also demonstrate that in patients suffering from SoJIA, NK cells show normal cytotoxicity, suggesting that immunological mechanisms involved in FHL and secondary HLH are distinct. In the second part of this manuscript, we aim at understanding the role of Styk1 serine/threonine/tyrosine kinase in NK cells’ regulation. NK cells are in charge of eliminating stressed, virally infected or transformed cells. Upon activation, they secrete large amounts of IFN-γ and TNF-α, thus bridging innate and adaptive immunity. Capabilities for recognition of target cells is endowed by the expression of numerous stochastically expressed activating and inhibitory receptors. The balance between activating and inhibitory signal allows for self-tolerance or activation upon engagement of abnormal cells. Activating and inhibitory receptor are germline encoded in two dense, large complexes, the Natural Killer Complex (NKC) and the Leukocyte Receptor Complex (LRC). At the moment of starting this work, we had recently identified that Styk1 was a signature transcript of NK cells. However, its function in NK cells and more generally in the immune system remains unknown. Nevertheless, its genetic localisation near the NKC and its potential implication in the PI3K-AKT pathway prompt that it may play a role in NK cell development and/or functions. In order to evaluate the role of Styk1 in NK cells’ regulation, we generated a mouse model in which its expression is abrogated. Our data confirms that amongst all immune subsets, Styk1 is specifically expressed by NK cells. Styk1 was also able to discriminate NK cells from other ILCs. In this study, we show that Styk1 invalidation lead to a decrease of activity in the AKT/mTOR pathway. However, NK cells development, homeostasis and function were surprisingly normal in Styk1 -/- mice
24
Sleater, Michelle Leigh. "Cellular and molecular effector mechanisms of islet allograft rejection /." Connect to full text via ProQuest. IP filtered, 2006.
Find full textAbstract:
Thesis (Ph.D. in Immunology) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 151-168). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
25
Wang, Xisheng. "Mechanisms of IFN-gamma-mediated Resistance against Development of Toxoplasmic Encephalitis." Diss., Virginia Tech, 2006. http://hdl.handle.net/10919/30268.
Full textAbstract:
Toxoplasma gondii, an obligate intracellular protozoan parasite, establishes a latent, chronic infection by forming cysts preferentially in the brain after replication of tachyzoites in various organs during the acute stage of infection. Chronic infection with T. gondii is one of the most common parasitic diseases in humans. The immune system is required for maintaining the latency of chronic infection. Reactivation of infection can occur in immunocompromised individuals, such as AIDS patients, which results in the development of life-threatening toxoplasmic encephalitis (TE). IFN-gamma-dependent, cell mediated immune responses play an essential role in preventing the reactivation of chronic infection of T. gondii in the brain. In my dissertation study, we examined the mechanisms of IFN-gamma-mediated prevention of TE by using models of reactivation of chronic infection in BALB/c mice. This strain of mouse is genetically resistant to T. gondii infection and establishes a latent chronic infection as do immunocompetent humans, and therefore provides an excellet model for this purpose.
Our laboratory previously demonstrated that both T cells and IFN-gamma-producing non-T cells are required for genetic resistance of BALB/c mice against development of TE. However, the function of T cells required for the resistance is still unclear. Therefore, in the present study, we examined whether IFN-gamma production or perforin-mediated cytotoxicity of T cells play an important role in their protective activity against TE. Immune T cells were obtained from infected IFN-gamma-knockout (IFN-g-/-), perforin-knockout (PO), and wild-type (WT) BALB/c mice, and transferred into infected, sulfadiazine-treated athymic nude mice which lack T cells but have IFN-gamma-producing non-T cells. Control nude mice that had not received any T cells developed severe TE due to reactivation of infection and died after discontinuation of sulfadiazine treatment. Animals that had received immune T cells from either PO or WT mice did not develop TE and survived. In contrast, nude mice that had received immune T cells from IFN-gamma-/- mice developed severe TE and died as early as control nude mice. T cells obtained from spleens of the animals that had received either PO or WT T cells both produced large amounts of IFN-gamma following stimulation with T. gondii antigens in vitro. In addition, the amounts of IFN-gamma mRNA expressed in the brains of PO T-cell recipients did not differ from those of WT T-cell recipients. These results indicate that IFN-gamma production, but not perforin-mediated cytotoxic activity, by T cells is required for prevention of TE in genetically resistant BALB/c mice.
In our attempt to identify a T cell population(s) that produces IFN-gamma in the brain and plays an important role for prevention of TE, we analyzed T cell receptor (TCR) Vb chain usage in T cells expressing IFN-gamma in the brains of infected BALB/c mice. We found T cells bearing TCR V beta8 chain to be the most frequent IFN-g-producing population in the brains of infected animals. To examine the role of IFN-gamma production by this T cell population for prevention of TE, V beta8+ immune T cells purified from spleens of infected BALB/c and IFN-g-/- mice were transferred into infected, sulfadiazine-treated athymic nude mice. After discontinuation of sulfadiazine treatment, control nude mice that had not received any T cells and animals that had received Vb8+ T cells from IFN-g-/- mice all died due to reactivation of infection (TE). In contrast, animals that had received the cells from WT mice survived. These results indicate that IFN-gamma production by Vb8+ T cells in the absence of any other T cell population can prevent reactivation of infection. Thus, V beta8+ T cells play a crucial role in genetic resistance of BALB/c mice to TE through their production of IFN-gamma. When V beta8+ immune T cells were divided into CD4+ and CD8+ subsets, a potent protective activity was observed only in the CD8+ subset whereas a combination of both subsets provided greater protection than did the CD8+Vb8+ population alone. These results indicate that CD8+ subset of V beta8+ T cells is a major afferent limb of IFN-gamma-mediated resistance of BALB/c mice against TE, although the CD4+ subset of the T cell population works additively or synergistically with the CD8+V beta8+ population.
T cells need to enter into the brains of infected mice to demonstrate their protective activity against TE. This migration is mediated, in part, by endothelial adhesion molecules. Since IFN-gamma is essential for preventing reactivation of chronic infection with this parasite in the brain, we examined whether this cytokine plays an important role in expression of lymphocyte and endothelial adhesion molecules and recruitment of T cells into the brain during chronic infection with T. gondii using IFN-g-/- and WT BALB/c mice. Although the number of cerebral vessels expressing intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) increased in both WT and IFN-g-/- mice following infection, there were more VCAM-1+ vessels in brains of infected WT than infected IFN-g-/- mice; in contrast, numbers of ICAM-1+ vessels did not differ between strains. We did not detect endothelial E-selectin, P-selectin, MAdCAM-1 or PNAd in any of the brains. Significantly fewer CD8+ T cells were recruited into brains of infected IFN-g-/- than WT mice. Treatment of infected IFN-g-/- mice with recombinant IFN-gamma restored the expression of VCAM-1 on their cerebral vessels and recruitment of CD8+ T cells into their brains, confirming an importance of this cytokine for up-regulation of VCAM-1 expression and CD8+ T cell trafficking. In infected WT and IFN-g-/- animals, almost all cerebral CD8+ T cells had an effector/memory phenotype (LFA-1high, CD44high and CD62Lneg) and approximately 38% were positive for a4b1 integrin (the ligand for VCAM-1). In adoptive transfer of immune spleen cells, pre-treatment of the cells with a monoclonal antibody against a4 integrin markedly inhibited recruitment of CD8+ T cells into the brain of chronically infected wild-type mice. These results indicate that IFN-g-induced expression of endothelial VCAM-1 and its binding to a4b1 integrin on CD8+ T cells is important for recruitment of the T cells into the brain during the chronic stage of T. gondii infection. Since we found strong expression of ICAM-1 on endothelia and LFA-1 on T cells in the brains of infected mice, LFA-1/ICAM-1 interaction, in addition to a4b1 integrin/VCAM-1 interaction, may also be involved in this process. As mentioned earlier, CD8+ T cells are crucial for prevention of TE in BALB/c mice. Therefore, IFN-gamma-mediated expression of VCAM-1 and its binding to a4b1 integrin for recruitment of CD8+ T cells may play a critical role in genetic resistance of BALB/c mice to development of TE.Ph. D.
26
Talbot-Honeck, Carole. "Excellence in the performing arts: A study of elite musicians' mental readiness to perform." Thesis, University of Ottawa (Canada), 1994. http://hdl.handle.net/10393/10348.
Full textAbstract:
Sixteen elite classical musicians from six countries were interviewed to explore and document their mental readiness to excel and to assess the relevance of Orlick's model of excellence (1989) to musical excellence. Five of Orlick's components were found to be common among elite musicians: an extremely high level of commitment, a clear focus on the music, an ability to refocus, highly developed imagery (or visualization) skills and constructive performance evaluation. Musicians do not have very specific or detailed mental preparation plans for practicing or for performing; they prefer to follow general guidelines. Three qualities were added to the list of skills/qualities required to excel in music: spontaneity, creativity and flexibility. Other determining factors in the musician's level of excellence were the nature of their goals, the perspective they carry into their musical endeavours and their abiding love and enjoyment of music. Problems encountered are discussed and future avenues of research are suggested.
27
Vasireddi, Mugdha. "Subversion of Natural Killer Cell Defenses Induced by a Deadly Zoonotic Virus." Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/biology_diss/65.
Full textAbstract:
B virus (Macacine herpesvirus 1, Cercopithecine herpesvirus 1, herpes B virus) is an Old World monkey simplex virus endemic in macaques. B virus infection in its natural host, macaque, is very similar to HSV-‐1 infection in humans causing mild or asymptomatic infection. On the other hand, zoonotic infection in humans results in death in the absence of early initiation of antiviral drugs. Viruses evade host immune responses in order to survive and propagate. Most herpes viruses including HSV-‐1 down-‐regulate major histocompatibility complex class I (MHC class I) surface expression on infected cells in order to prevent CD8+ T-‐cell recognition and subsequent cell lysis. MHC class I molecules bind to the inhibitory receptors of NK cells and prevent NK cell activity. Thus, this mechanism protects HSV-‐1 infected cells from CD8+ T-‐cell lysis, making them sensitive to natural killer (NK) cell cytotoxicity. To investigate if B virus pathogenicity is a result of novel immune evasion mechanisms employed by B virus, we determined NK cell regulation during B virus infection. To this end, our experiments demonstrate that B virus does not down-‐ regulate MHC I expression as effectively as HSV-‐1, leading us to hypothesize that B virus in-‐ fected cells are resistant to NK cell activity. We examined the expression of MHC I chain related genes (MICA/ MICB), which are activation ligands to NKG2D receptors on NK cells. Our results show that there is no significant difference in MICA and MICB expression between HSV-‐1 and B virus infected cells. Furthermore, we tested for the up-‐regulation of cytokines and chemokines responsible for NK cell activation and migration. Our results indicate a significant up-‐regulation of IFN-‐α from PBMCs co-‐cultured with HSV-‐1 infected cells, which plays an important role in activating NK cells. NK cells within these PBMCs up-‐regulate perforin release indicative of NK cell activity. PBMCs co-‐cultured with B virus infected cells do not up-‐regulate any cytokines or chemokines responsible for NK cell activity. As a result the NK cells within these PBMCs do not significantly up-‐regulate perforin release. These results demonstrate that B virus employs a novel immune evasion mechanism to subvert NK cell activity.
28
Kinney, Daryl Wayne. "The Effect of School Performing Ensemble Participation on the Ability to Perform and Perceive Expression in Music." The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1392813859.
Full text
29
Andrews, Stuart L. "Performing histories : the politics of performing the past." Thesis, Lancaster University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420696.
Full text
30
Kelly, Traci. "Performing Intersubjectivity." Thesis, University of Reading, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525121.
Full text
31
Cornea, Christine. "Performing cyborgs." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364752.
Full text
32
Reynoso, Humberto. "Performing Binaries." CSUSB ScholarWorks, 2015. https://scholarworks.lib.csusb.edu/etd/252.
Full textAbstract:
I take a critical view of sociopolitical and cultural issues dealing with homoeroticism andgay politics. I explore gender theories in order to further understand what it means to bemasculine or feminine and how it affects my placement in society. I use art as a tool forexpressing sexual freedom while questioning traditional sexual identity. I'm interested in exploring ideas of the oppressor and the oppressed, and how power becomes an inevitable force (in every society) that creates a hierarchy, consequently establishing control. But what is power? According to various definitions, power is an entity that possesses and or exercises authority or influence. I want to focus on this idea of exercising authority, which one can argue we need, but why? To prevent chaos or is it to control a society? What about exercising influence? Do we need an influence exercised upon us? Or does that make us subjected to another person's subjective point of views? These are questions that I directly or indirectly ask with my work in relationship to gender, gender roles, and sexual orientation. I am interested in Judith Butler's theory in performing gender, and how in performing gender, one assumes social hierarchy of power depending on what gender we are performing. If I am a man performing as a man then I am treated differently by society than if I am a woman performing as a woman. But what happens if I am a man performing as a man who prefers men as lovers, or a woman who prefers other woman as lovers? In what context is this situation accepted by our society? And is it different for men and women? And why? What does it mean to be a man? What does it mean to be a woman, within the context of performance? Then taking it a step further and argue that we are all performing subjective ideas constructed by social norms.
33
Fine, Jenny. "Performing Tenderness." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1276799884.
Full text
34
Scott, Jessica Mae. "A Comparison of Attitudes Towards Time Management, Usage of Time, and Self-Expression by High-Performing and Low-Perfoming Students at Brigham Young University." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3365.
Full textAbstract:
Time log data (time-spent and adjective evaluations), a six question survey about time management attitudes, and the Adult Self Expression Scale (behavioral and situational subscales), were examined regarding how well each predict GPA. This paper contains two studies. The first study uses canonical correlations to examine the natural relationships between GPA and the five sets of predictor variables. The second study is hypothesis testing with regard to four groups: males and females on academic probation, and males and females with high GPAs. The effects of academic probation and gender on the same four sets of variables are examined: time spent on selected activities, adjective evaluations of activities, a six question survey, and the behavioral and situational dimensions of the ASES. The six question survey shows the strongest connection with GPA. The time log data, while not very compelling, shows promise for future research. Of all of the variable sets, the ASES is the weakest predictor of GPA.
35
Onaisi, Atef. "Mécanismes de rupture d'une plaque percée en mécanique des roches en relation avec un forage pétrolier." Châtenay-Malabry, Ecole centrale de Paris, 1989. http://www.theses.fr/1989ECAP0108.
Full textAbstract:
On a cherche les mécanismes de rupture d'une plaque de roche munie d'un trou cylindrique et soumise à un chargement uniaxial. La connaissance des mécanismes nous est nécessaire lorsqu'on veut simuler la rupture sous des conditions de chargement plus complexes (un forage pétrolier par exemple) à l'aide des modèles de calcul numérique. Le travail comporte un examen des travaux antérieurs sur la rupture en parois des puits, des essais triaxiaux sur un grès et une roche calcaire, des essais de chargement uniaxial sur plaque percée et une interprétation des essais triaxiaux et des essais sur plaques. Les déformations des plaques ont été mesurées expérimentalement au moyen de jauges extensometriques (4 à 17 jauges). La rupture des plaques a été examinée sur des plaques minces prélevées dans les zones fissurées ou rompues
36
Larsen, Jonas. "Performing tourist photography /." Roskilde : Department of Geography and International Development Studies, Roskilde University, 2004. http://hdl.handle.net/1800/788.
Full text
37
Correro, Augustine III. "Performing Tennessee Williams." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2713.
Full textAbstract:
This thesis is dedicated to illustrating the unique challenges of staging works by the playwright Tennessee Williams, and to making suggestions on how to avoid common pitfalls in production, performance, and direction of his plays. It uses evidence from the playwright’s various biographical works as well as insight and conjecture from the author’s experience to illuminate these challenges and help the reader to avoid hackneyed or ineffective staging practices. It touches on the effect of film adaptations on stage performances; the typical portrayal of American Southern characters onstage; the aural ramifications of Williams’s poetry to a now-visually-centered audience; stylistic elements similar to Williams’s contemporaries, including Rice, Brecht, O’Neill, and others; the delicacy of Williams’s signature meter and rhythm in his plays; dramaturgical groundwork in the playwright’s intentions; and a systemization of archetypical Williams characters. This thesis does not prescribe a cut-and-dried set of rules and regulations for performing Williams’s works, for the simple reason that the Williams canon is so diverse that no singular set of “tricks” will be effective in every play. Furthermore, the author understands that a producer, director, or actor will not find use in all facets of a rigid “system”. The thesis does outline a number of practices whose aims are to make productions more effective from an integral perspective. There are exercises to attempt, questions to pose, and matters to consider in the staging of Williams’s plays during any part of production—from in-class reading to designing the scenery, and from deciding why to put a Williams play in a season to the living moments of an actor’s performance. The thesis aims to be helpful, informative, and accessible, rather than doctrinaire: much like the playwright’s works, its purpose is to illuminate dark corners of something that viewers think they already fully understand.
38
Gonzales, Melinda Arteaga. "Performing Culture, Performing Me: Exploring Textual Power through Rehearsal and Performance." Thesis, University of North Texas, 2005. https://digital.library.unt.edu/ark:/67531/metadc4965/.
Full textAbstract:
This thesis project explores Chicana feminist Gloria Anzaldúa's notion of a new mestiza consciousness, in which the marginalized ethnic American woman transcends her Otherness, breaks down the borders between her different identities, and creates a Thirdspace. Through the rehearsal and performance process, three ethnic American women employed Robert Scholes' model of textuality-the consumption and production of texts-as a framework to construct a new mestiza consciousness, and create a Thirdspace. The project set to determine what strategies were significant rehearsal techniques for encouraging the cast members to exercise textual power and claim a new mestiza identity, a Thirdspace. The results reveal four overarching factors involved in assuming textual power through rehearsal and performance in the production-building trust, having appropriate skills, assuming ownership and responsibility, and overcoming performance anxiety. The discussion addresses the direct link between Thirdspace and Scholes' notion of production of original texts.
39
Esquibel, Elena. "Performing Race, Performing History: Oral Histories of Sundown Towns in Southern Illinois." OpenSIUC, 2011. https://opensiuc.lib.siu.edu/dissertations/356.
Full textAbstract:
Sundown towns are communities with a history of excluding African Americans and that are predominantly White on purpose. Although sundown towns have inevitably changed over time, a number of them continue to be alarmingly White, and their reputations continue to persist. Sundown towns are widespread across the U.S. and despite their prevalence, very little research exists on the topic. Furthermore, sundown towns were largely maintained through oral tradition. In this dissertation, I explore oral history interviews with community residents about the history of sundown towns in southern Illinois. Based on over two years of fieldwork, I examine how community narratives construct present realities of sundown towns in new and nuanced ways. I am also interested in how these narratives function. I argue that race is central to investigating the history of sundown towns and use performance as an analytical tool to understand racial dimensions in community members' stories. I examine how everyday community narratives reveal racialized performances and construct current manifestations of sundown towns. I further examine the process of translating these narratives into a staged performance. Ultimately, I argue that exploring everyday community narratives from the field to the stage allows a heuristic view of the living history of sundown towns. My approach to this study is deeply informed by critical performance ethnography and Critical Race Theory. These methods work together as modes of inquiry that enable analysis of community narratives as well as my role as a researcher, with the aspiration of social change. I enter this research with the agenda to deconstruct racist structures and add to social justice discourses. In this dissertation, I strive to create space for dialogue about sundown towns, race, and racism with various audiences and create possibilities for disrupting this history.
40
Richards, Alison 1951. "Bodies of meaning : issues of field and habitus in contemporary Australasian theatrical performance practice." Monash University, School of Literary, Visual and Performance Studies, 2003. http://arrow.monash.edu.au/hdl/1959.1/7815.
Full text
41
O'Shea, Margaret. "Embodying and performing sustainability." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43179.
Full textAbstract:
This dissertation explores the theoretical and methodological implications of including embodiment and performance theory in sustainability theory and practice, and demonstrates the advantages and difficulties of embodied sustainability research in two case studies of communities performing sustainability practices. The potential influence of an embodied approach to participatory governance theory in light of the anticipated sustainability transition is also investigated. The fundamental characteristics of embodiment are determined and a performance typology derived from performance theory is developed to help guide case study analysis and interpretation. The first case study investigates the perceptions, actions, and possible transformations of members of a theatrical group who tour British Columbia by bicycle. The second case study recruits the creative participation of members of a recycling initiative in Vancouver’s Downtown Eastside in a photographic project designed to elicit their embodied experiences of sustainability within their daily actions.
This research is premised on the argument that sustainability can be usefully conceived of as a property that emerges from collaborative practices and dialogue (i.e., procedural sustainability), rather than simply as a set of expert-defined imperatives (i.e., substantive sustainability). Incorporating the embodiment paradigm into research on sustainability suggests that such research should be interactive by way of active and creative participation by citizens. Furthermore, embodiment and sustainability are experienced as deeply socially and culturally embedded phenomena, which should be reflected in sustainability research through a strong integration of ecological, economic, social, and cultural concerns. Performance theory provides a theoretical frame and methodological direction that centres on the socially- and culturally-mediated experiencing body. Findings from the case studies, and application of findings to participatory governance theory, confirm that: framing sustainability as a procedurally emergent property of social practices is appropriate and productive at the community-scale; applying a performance lens to sustainability practices reveals complex performative dimensions of socially-situated embodied experience; and participatory processes for embodied engagement, specifically arts-based methods, have great potential to provide novel opportunities for engagement with governments and policy processes.
42
Schindeler, Marda, and University of Lethbridge Faculty of Arts and Science. "Alberta performing arts policy." Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 1998, 1998. http://hdl.handle.net/10133/77.
Full textAbstract:
Alberta's first arts legislation, the Cultural Development Act, was passed in 1946. It was followed by numerous policy initiatives to support the arts, including creation of facilities for training of artists, development of agencies and agreements to deal with arts funding, enactment of regulations to guide arts institutions, and creation of various Departmental structures depending on organizational location of this policy sector. The thesis examines the historical evolution of performing arts policy in Alberta from 1905 to 1997 to identify government activities, shifts in policy-making, and methods of implementation. The study utilizes Paul Sabatier's advocacy coalition approach, which treats public policy as determined by the dynamics of the advocacy coalition within a policy sector and the manner in which external factors and system parameters steer policy development. This study concludes that Alberta performing arts policy has largely developed within the context of meta public policies emphasizing economic development and provincial statebuilding.iii, 97 leaves : ill. ; 28 cm.
43
Schindeler, Marda. "Alberta performing arts policy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape15/PQDD_0006/MQ38440.pdf.
Full text
44
Cheng, Kai-mau Joe, and 鄭佳茂. "Chaozhou Opera performing centre." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1995. http://hub.hku.hk/bib/B3198230X.
Full text
45
Cheng, Kai-mau Joe. "Chaozhou Opera performing centre." Hong Kong : University of Hong Kong, 1995. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25945981.
Full text
46
Human, Martie. "Encore - performing arts centre." Diss., Pretoria : [s.n.], 2003. http://upetd.up.ac.za/thesis/available/etd-11212003-110815.
Full text
47
Nordenlöw, Frida. "The Everyday Performing Textiles." Thesis, Konstfack, Textil, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:konstfack:diva-7820.
Full textAbstract:
Living as a human being in the 21st century is a more or less constant three-dimensional textile experience. Textiles have a continuous proximity to our bodies as clothing but also as an essential material in our dwellings, both with practical and emotional functions. The Everyday Performing Textiles derives from my deep interest in the qualities and embedded connotations of textiles, the stuff that affectively shapes our material reality. These soft things play different roles in our lives, as parts of a web of function and meaning. In this thesis I focus on the unobtrusive position of everyday textiles, searching to reflect upon the significance and substance they have within our homes. I predicate that our wellbeing is deeply dependent and connected to the comfort of textiles – it being an emotional material as much as a physical. I use the expectations of materiality as a method, balancing between the familiar and the strange, to challenge and expand our perception of cloth, both as a statement and a query of its value in modern society. I depict everyday textiles in a skewed way, mixing the realistic and the unrealistic, to create an expanded perception of them – playing with their immanent, possibly unspoken, expectations. The Everyday Performing Textiles is an acknowledgement of our textile reality – the existence of this interactive, interdependent relationship in our everyday practice of living.
48
Bouchard, Gianna. "Performing the anatomised body." Thesis, University of Roehampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.722582.
Full text
49
Harkin, Patrick. "Prime, Perform, Recover." VCU Scholars Compass, 2017. https://scholarscompass.vcu.edu/etd/5276.
Full textAbstract:
This thesis examines the formal and conceptual framework of my artistic practice as it culminated in the installation of my thesis exhibition, Prime, Perform, Recover. My exhibition seeks to operate as an analysis and critique of the separation inherent in media presentation and rhetoric surrounding natural disasters.
I utilize the aesthetics and vocabulary of disaster capitalism and prepping culture in order to pose direct questions about ecological and social change. I examine the role of images within mass media image production as an all encompassing Now-Time. In this paper I describe frameworks that my practice proposes as potential solutions to these problems, and I position my research in the context of artists and artworks that have influenced me and operate within similar channels as my own.
50
Gill, Zachary Whitman. "Soldiers performing/performing soldiers spectacular catharsis, perpetual rehearsal, and theatricality in the US infantry /." Diss., [La Jolla] : [Irvine] : University of California, San Diego ; University of California, Irvine, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3359846.
Full textAbstract:
Thesis (Ph. D.)--University of California, San Diego and the University of California, Irvine, 2009.Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 239-249).