Dissertations / Theses: 'Visceral and Lymphoid organs'

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Taves, Matthew D. "Local glucocorticoid regulation in avian and murine lymphoid organs." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/54542.

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Glucocorticoids are steroid hormones that circulate in the blood to coordinate organismal physiology. They have pleiotropic effects, regulating metabolic, cardiovascular, neural, and immune function. While glucocorticoids are classically thought to be secreted exclusively by the adrenal glands, evidence suggests that different organs may be able to autonomously regulate their local glucocorticoid levels via local production. Local production may be important when circulating glucocorticoids are low or absent, such as in early life of altricial young, which are unable to care for themselves. Immune (lymphoid) organs are particularly interesting candidates for tissue-specific regulation of glucocorticoid levels, as glucocorticoids are necessary for early-life immune development in altricial young. In this dissertation, I present a series of studies using birds and mice to examine whether tissue- specific regulation of glucocorticoids occurs in lymphoid organs. In brief, I report that a) glucocorticoids are locally elevated in lymphoid organs of newly-hatched altricial but not precocial birds, b) glucocorticoids are locally elevated in lymphoid organs of neonatal altricial mice, and c) lymphoid organs of both neonatal and adult mice synthesize glucocorticoids from other steroid precursors. Local glucocorticoid production in lymphoid organs may function to ensure production of functional lymphocytes, and factors that alter lymphoid glucocorticoid levels may play a role in programming the overall immune reactivity. Science, Faculty of Zoology, Department of Graduate

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Steinthal, Nathalie Pauline Elizabeth. "Exploring the role of CD248/endosialin/TEM-1 on lymphoid stromal cells in secondary lymphoid organs." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7409/.

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CD248 is a pericyte-associated, mesenchymal stem cell (MSC) marker that is highly expressed during embryological life. This expression is down regulated during development, becoming restricted on lymphoid stroma to the capsule, but reappearing during inflammation, as well as in a number of disease states (Lax et al., 2007). CD248 has been shown to play a role in controlling the differentiation ofMSC to osteoblasts, both in vitro and in vivo, achieving this effect by modulating PDGFRsignalling, as treatment with the PDGFRinhibitor imatinib mesylate phenocopies the effects seen in the CD248·;. mouse (Naylor et al., 2012). Here we present evidence that CD248 is involved in the differentiation of MSC, via PDGFRsignalling, into lymphoid stroma progenitors both in vitro and in vivo. In adult mice expression of CD248 is detected on FDCs following immunisation. Using CD248·1- mice, we observe that FDC networks in CD248·1- mice do not form normally and lack the reticular, dendrite-like structure typical ofFDCs. This defect associates with a reduction in the functionality of the germinal centres. Embryonic development of lymph node stroma occurs in a stepwise manner with progressive upregulation of VCAM and ICAM on resident mesenchyme. In the adult stroma, recent work has established links between different stromal cell subtypes; Jarjour eta/. (2014) used a fate mapping technique to discover that marginal reticular cells are able to differentiate to follicular dendritic cells in response to immune challenge. Contrasting evidence shows that FDC in the spleen derive from ubiquitous perivascular precursors, likely to be pericytes (Krautler et al., 2012).

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Motallebzadeh, Reza. "Tertiary lymphoid organogenesis in solid organ transplantation." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608121.

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Andrade, Marina Elizabeth Barbosa. "Growth curves of the visceral organs of Saanen goats /." Jaboticabal, 2017. http://hdl.handle.net/11449/151571.

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Orientador: Izabelle Auxiliadora Molina de Almeida Teixeira Coorientador: Carla Joice Härter Banca: Rafael Fernandes Leite Banca: Kleber Tomas de Resende Resumo: Este trabalho foi realizado utilizando informações de 7 estudos, em que foram ajustadas curvas de crescimento ao desenvolvimento dos órgãos do sistema visceral de fêmeas, machos castrados e machos inteiros da raça Saanen de 0,5 a 19,5 meses de idade. Inicialmente, foram avaliados oito modelos: Regressão linear simples; Quadrático; Monomolecular; Brody; Von Bertalanffy; Logística; Gompertz; e Richards. Os dados dos órgãos viscerais (fígado, pâncreas, baço, rúmen-retículo, omaso, abomaso, intestino delgado e intestino grosso) e tecido adiposo mesentérico (TAM), foram ajustados nos modelos usando o procedimento NLMIXED do SAS. O melhor modelo ajustado foi escolhido com base no Critério de Informações Akaike corrigido para pequenas amostras (AICc) e nos coeficientes de correlação de concordância (CCC). Após a escolha do modelo que melhor ajustou a curva de crescimento dos órgãos viscerais avaliados, modelamos a variância buscando um melhor ajuste. Os parâmetros dos modelos para cada sexo foram comparados utilizando o comando CONTRAST (p < 0,10). Em geral, o modelo que melhor descreveu o crescimento de órgãos do sistema visceral foi o logístico (menor AICc e maior CCC). Quando os órgãos foram expressos em gramas, o sexo não influenciou os parâmetros das equações para predição do crescimento dos órgãos avaliados (p > 0,10), exceto o MAT (p < 0,02); em que as fêmeas apresentaram menor taxa de deposição comparada aos machos inteiros e castrados (0,318 ± 0,034 vs 0,659 ± 0,062), e um ... (Resumo completo, clicar acesso eletrônico abaixo) Abstract: This work was performed gathering information of 7 studies, in which growth curves were fitted to the visceral organs of female, intact male, and castrated male Saanen goats from 0.5 to 19.5 months old. Initially, eight models were assessed: Monomolecular; Simple linear regression; Quadratic; Monomolecular; Brody; Von Bertalanffy; Logistics; Gompertz; and Richards. Data of the visceral organs (liver, pancreas, spleen, rumen-reticulum, omasum, abomasum, small intestine, and large intestine) and mesenteric adipose tissue (MAT) were fitted in the models using NLMIXED procedure of SAS. The best fitted model was choosing based on the Akaike Corrected Information Criterion for small samples (AICc) and values and the concordance correlation coefficient (CCC). After choosing the model that best fitted the growth curve of the evaluated visceral organs, we modelled the variance seeking a better fit. Parameters of the models for each sex were compared using the CONTRAST statement (p < 0.10). Overall, the model that best described visceral organ growth was the logistic (i.e., lower AICc and higher CCC). When organs were expressed in grams, the sex did not influence the parameters of equations to predict the growth of the evaluated organs (p > 0.10), except for TAM (p < 0.02); females presented a lower deposition rate compared to intact males and castrated males (0.318 ± 0.034 vs 0.659 ± 0.062), and a inflection point higher than intact males and castrated males (7.65 vs 3.69 months). However, this difference between the sexes is not found when TAM is expressed in % to empty body weight (EBW). Irrespective of sex, at the beginning of growth, liver stood for 2.75 ± 0.113 % of EBW, grew (g) at a maximum rate of 0.531 ± 0.062, and its inflection point of the curve occurred at 1.7 months. The gastrointestinal t... (Complete abstract click electronic access below) Mestre

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Andrade, Marina Elizabeth Barbosa [UNESP]. "Growth curves of the visceral organs of Saanen goats." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/151571.

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Submitted by MARINA ELIZABETH BARBOSA ANDRADE null (marina.elizabeth.15@hotmail.com) on 2017-09-05T20:54:30Z No. of bitstreams: 1 Dissertacao_Marina_Elizabeth_Barbosa_Andrade.pdf: 1779690 bytes, checksum: 51b157ca3cbbdb6dc57ecd5a6207a396 (MD5) Rejected by Luiz Galeffi (luizgaleffi@gmail.com), reason: Solicitamos que realize uma nova submissão seguindo a orientação abaixo: A folha de aprovação deve ser inserida na página subsequente à ficha catalográfica. Corrija esta informação e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2017-09-06T16:31:12Z (GMT) Submitted by MARINA ELIZABETH BARBOSA ANDRADE null (marina.elizabeth.15@hotmail.com) on 2017-09-06T19:11:35Z No. of bitstreams: 1 Dissertacao_Marina_Elizabeth_Barbosa_Andrade.pdf: 1979789 bytes, checksum: e5046942b9fb3e5014e6fa1eadfcd9db (MD5) Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-09-11T19:35:47Z (GMT) No. of bitstreams: 1 andrade_meb_me_jabo.pdf: 1979789 bytes, checksum: e5046942b9fb3e5014e6fa1eadfcd9db (MD5) Made available in DSpace on 2017-09-11T19:35:47Z (GMT). No. of bitstreams: 1 andrade_meb_me_jabo.pdf: 1979789 bytes, checksum: e5046942b9fb3e5014e6fa1eadfcd9db (MD5) Previous issue date: 2017-07-10 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Este trabalho foi realizado utilizando informações de 7 estudos, em que foram ajustadas curvas de crescimento ao desenvolvimento dos órgãos do sistema visceral de fêmeas, machos castrados e machos inteiros da raça Saanen de 0,5 a 19,5 meses de idade. Inicialmente, foram avaliados oito modelos: Regressão linear simples; Quadrático; Monomolecular; Brody; Von Bertalanffy; Logística; Gompertz; e Richards. Os dados dos órgãos viscerais (fígado, pâncreas, baço, rúmen-retículo, omaso, abomaso, intestino delgado e intestino grosso) e tecido adiposo mesentérico (TAM), foram ajustados nos modelos usando o procedimento NLMIXED do SAS. O melhor modelo ajustado foi escolhido com base no Critério de Informações Akaike corrigido para pequenas amostras (AICc) e nos coeficientes de correlação de concordância (CCC). Após a escolha do modelo que melhor ajustou a curva de crescimento dos órgãos viscerais avaliados, modelamos a variância buscando um melhor ajuste. Os parâmetros dos modelos para cada sexo foram comparados utilizando o comando CONTRAST (p < 0,10). Em geral, o modelo que melhor descreveu o crescimento de órgãos do sistema visceral foi o logístico (menor AICc e maior CCC). Quando os órgãos foram expressos em gramas, o sexo não influenciou os parâmetros das equações para predição do crescimento dos órgãos avaliados (p > 0,10), exceto o MAT (p < 0,02); em que as fêmeas apresentaram menor taxa de deposição comparada aos machos inteiros e castrados (0,318 ± 0,034 vs 0,659 ± 0,062), e um ponto de inflexão superior ao dos machos inteiros e castrados (7,7 vs 3,7 meses). No entanto, essa diferença entre os sexos não é encontrada quando o MAT é expresso em % ao peso do corpo vazio (PCV). Independentemente do sexo, no início do crescimento, o fígado representou 2,75 ± 0,113 % do PCV, cresceu (g) a uma taxa máxima de 0,531 ± 0,062, e o ponto de inflexão de sua curva ocorreu em 1,7 meses. O trato gastrointestinal (TGI) representou 9,14 ± 0,493 % PCV, e à medida que os animais cresceram o TGI diminuiu sua porcentagem em relação ao PCV a uma taxa constante de 0,135 ± 0,046 %. Considerando o período avaliado, em geral, o rúmen-retículo e o intestino grosso aumentaram sua porcentagem em relação ao PCV e TGI, enquanto o abomaso e o intestino delgado diminuíram sua porcentagem em relação ao PCV e TGI, à medida que o animal crescia. O rúmen-retículo e o intestino grosso, que estão diretamente relacionados à digestão de alimentos sólidos, apresentaram maiores taxas de crescimento nos dois primeiros meses de vida. Os resultados evidenciaram que o sexo não afeta o crescimento de órgãos do sistema visceral (g), exceto para MAT, porém, quando olhamos em % PCV alguns órgãos mostram diferenças entre os sexos, como o fígado, abomaso, intestino delgado, intestino grosso e intestinos. O conhecimento da curva de crescimento dos órgãos viscerais pode ser muito útil para melhorar a compreensão de seu impacto sobre as exigências nutricionais desses animais, e ser utilizado para otimizar ou desenvolver um plano nutricional adequado para cada fase de crescimento, como também auxiliar os produtores a desenvolver planos estratégicos em um rebanho de caprinos, como a melhor idade para desmame e abate desses animais. This work was performed gathering information of 7 studies, in which growth curves were fitted to the visceral organs of female, intact male, and castrated male Saanen goats from 0.5 to 19.5 months old. Initially, eight models were assessed: Monomolecular; Simple linear regression; Quadratic; Monomolecular; Brody; Von Bertalanffy; Logistics; Gompertz; and Richards. Data of the visceral organs (liver, pancreas, spleen, rumen-reticulum, omasum, abomasum, small intestine, and large intestine) and mesenteric adipose tissue (MAT) were fitted in the models using NLMIXED procedure of SAS. The best fitted model was choosing based on the Akaike Corrected Information Criterion for small samples (AICc) and values and the concordance correlation coefficient (CCC). After choosing the model that best fitted the growth curve of the evaluated visceral organs, we modelled the variance seeking a better fit. Parameters of the models for each sex were compared using the CONTRAST statement (p < 0.10). Overall, the model that best described visceral organ growth was the logistic (i.e., lower AICc and higher CCC). When organs were expressed in grams, the sex did not influence the parameters of equations to predict the growth of the evaluated organs (p > 0.10), except for TAM (p < 0.02); females presented a lower deposition rate compared to intact males and castrated males (0.318 ± 0.034 vs 0.659 ± 0.062), and a inflection point higher than intact males and castrated males (7.65 vs 3.69 months). However, this difference between the sexes is not found when TAM is expressed in % to empty body weight (EBW). Irrespective of sex, at the beginning of growth, liver stood for 2.75 ± 0.113 % of EBW, grew (g) at a maximum rate of 0.531 ± 0.062, and its inflection point of the curve occurred at 1.7 months. The gastrointestinal tract (GIT) stood for 9.14 ± 0.493 % EBW, and as the goats grew the GIT decreased its percentage in relation to the EBW at a constant rate of 0.135 ± 0.046 %. Considering the evaluated period, in general rumen-reticulum and large intestine increased their percentage in relation to EBW and GIT, whereas abomasum and small intestine decreased their percentage in relation to EBW and GIT, as animal grew. The rumen-reticulum and large intestine, which are directly related to the digestion of solid foods, presented higher growth rates in the first two months of life. The results highlighted that sex does not affect the growth of visceral organs (g), except for TAM. However, when we look at % EBW, some organs show differences between the sexes, such as the liver, abomasum, small intestine, large intestine and Intestines. Knowledge of the growth curve of the visceral organs can be very useful in improving the understanding of their impact on the nutritional requirements of these animals and can be used to optimize or develop a nutritional plan suitable for each growth phase, but also to help producers develop strategic plans for a herd of goats, such as the best age for weaning and slaughtering these animals.

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Pham, Trung Hoang Minh. "Characterization of the mechanism for lymphocyte egress from secondary lymphoid organs." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3378503.

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鄺懿珩 and Yi-hang Agnes Kwong. "Spatial distribution pattern of murine CD34 mRNA+ cells in hematopoietic and lymphoid organs." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31237174.

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Kwong, Yi-hang Agnes. "Spatial distribution pattern of murine CD34 mRNA+ cells in hematopoietic and lymphoid organs /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19471087.

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Silva, Marco Antonio Ferreira da. "Ultrasonographic assessment in pregnant queens : study of fetal heart rate and lymphoid organs." reponame:Repositório Institucional da UFPR, 2017. http://hdl.handle.net/1884/53522.

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Orientadora : Profª. Drª. Tilde Rodrigues Froes Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Agrárias, Programa de Pós-Graduação em Ciências Veterinárias. Defesa: Curitiba, 29/03/2017 Inclui referências : f. 46-49 Resumo: O presente estudo baseia-se na análise ultrassonográfica no terço final da gestação em gatas, abordando avaliações que possa dar suporte ao médico veterinário imaginologista frente às mudanças da frequência cardíaca fetal e novos dados sobre à organogênese. O trabalho foi dividido em dois capítulos independentes. No primeiro capítulo o enfoque da pesquisa foi no monitoramento da frequência cardíaca fetal no terço final da gestação para detecção de acelerações e desacelerações, fenômeno este descrito em humanos e recentemente descrito em cães. Essas mudanças causadas na frequência cardíaca fetal podem estar relacionadas às contrações uterinas e estão fortemente conectadas ao momento pré-parto. Esse trabalho demonstrou que tais oscilações da frequência cardíaca fetal acontecem em fetos felinos e podem ser utilizados como uma ferramenta na previsão do parto. Devido a evolução dos aparelhos ultrassonográficos, a alta resolução melhora a avaliação de estruturas muito pequenas no feto, o que possibilitaria a identificação de órgãos ainda não descritos na literatura. Por esse motivo, o segundo capítulo descreve em qual fase gestacional da gata há o aparecimento de órgãos linfoides. Fizemos uma avaliação descritiva do timo e do baço, o que pode contribuir para avaliação desses órgãos em outras espécies. Palavras-chave: gata, gestação, ultrassonografia fetal, frequência cardíaca fetal, organogênese Abstract:The main of research is based on ultrasonographic analysis in the final third of gestation in cats, addressing evaluations that may support the veterinarian's radiologist in the fetal heart rate changes and new data of organogenesis. Therefore, the study was divided into two chapters. In the first chapter, the focus of the research was on the fetal heart rate monitoring in the final third of gestation to detect accelerations and decelerations, a phenomenon described in humans and recently described in dogs. These changes in fetal heart rate may be related to uterine contractions and are strongly connected to the prepartum time. This work has demonstrated that such fetal heart rate oscillations occur in feline fetuses and can be used as a tool in predicting delivery. Due to the evolution of ultrasound devices, the high-resolution image improves the evaluation of tiny structures in the fetus, which would allow the identification of organs not yet described in the literature. For this reason, the second chapter describes in which gestational phase of the cat there is the appearance of lymphoid organs. We made a descriptive evaluation of the thymus and spleen, which may contribute to the assessment of these organs in other species. Keywords: cat, pregnancy, fetal ultrasound, fetal heart rate, organogenesis

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Benechet, Alexandre. "Dynamic of the effector T cells egress from secondary lymphoid organs after infection." Paris 7, 2014. http://www.theses.fr/2014PA077126.

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Une réponse immunitaire efficace va dépendre de la migration des cellules immunitaires à l'intérieur et entre les tissus lymphoïdes. Notre compréhension des facteurs impliqués dans la migration des lymphocytes T effecteurs antigen-spécifiques après une infection reste incomplète. La sortie des T effecteurs du ganglion drainant est une des étapes essentielles dans l'éradication potentielle du virus au site de l'infection. Bien qu'il soit connu que le récepteur au shingosine-1- phosphate (S1PR1) contrôle la sortie des T naïfs, son influence sur l'émigration des T effecteurs après infection reste obscure. Dans cette étude, nous avons dans un premier temps utilisé la technique de marquage au complexe d'histocompatibilité majeur (CHM) Tétramérique in-situ, ainsi que l'imagerie intra vitale d'un modèle de souris rapporteur granzyme B (GzmB) YFP afin de décrire le panel migratoire des T antigène-spécifiques dans le ganglion drainant après une infection virale localisée. Les T effecteurs localisent premièrement au paracortex tôt après l'infection puis enfin migrent à la périphérie du ganglion. Une fois en périphérie, les effecteurs vont emprunter les sinus lymphatiques corticaux ainsi que medullaires pour émigrer du ganglion. De plus, afin d'investiguer le role de S1PR1 dans la dynamique des T effecteurs nous avons développé une souris déficiente spécifiquement dans les T effecteurs dont la délétion est contrôlée dans le temps après infection. En utilisant ce modèle unique nous avons clairement démontré que même, en l'absence de signaux de rétention comme CCR7 et CD62L, S1PR1 est le signal essentiel à la sortie des T effecteurs du ganglion drainant An effective immune response depends on the large-scale, but carefully regulated migration of cells within and between lymphoid tissues. Our understanding of the factors that regulate the anatomical program followed by antigen-specific T cells during an infection remains incomplete. Egress of effector T cell from the draining lymph node (dLN) is one of the essential steps for the eventual eradication of the pathogen at the infection site. Although it is known that sphingosine-1-phosphate receptor 1 (S1PR1) controls naive T cell exit, how S1PR1 influences the emigration of effector T cells after infection is not well understood. Herein, by using both in-situ major histocompatibility complex (MHC)-tetramer staining and intravital imaging of a granzyme B (GzmB) YFP reporter mouse, we mapped the endogenous antigen-specific CD8 T cell response after localized viral infection in the dLN. In fact, we observed the localization of effector T cells in the paracortex early after infection, followed by the migration to the periphery. Notably, they exit the dLN via the medullary and cortical lymphatic sinuses. Furthermore, to assess the role of S1PR1 in their dynamic behavior, we generated a conditional GzmB YFP deficient mice to disrupt S1PR1 signals specifically and temporally in effector CD8 T cells after infection. Using this unique model we clearly demonstrate that after infection, even in the absence of retention signals such as CCR7 and CD62L S1PR1 signaling is the overriding factor that regulates effector T cell emigration from the dLN

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Cui, Guangwei. "Characterization of the IL-15 niche in primary and secondary lymphoid organs in vivo." Kyoto University, 2015. http://hdl.handle.net/2433/199210.

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Leigh, Roger. "The role of soluble growth factors and inhibitors in the vascularisation of lymphoid organs." Thesis, University of York, 2011. http://etheses.whiterose.ac.uk/2248/.

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Lymph nodes contain complex vascular networks composed of lymphatic and blood vessels. The blood vasculature contains specialised high endothelial venules functioning to permit the efficient entry of blood-borne lymphocytes into the node, while the lymphatics contain antigen-presenting cells draining from tissues. In contrast to the well understood cellular interactions and signalling mechanisms driving development of the stromal networks upon which immune cell interactions occur, the processes by which the complex vascular networks develop are poorly characterised. This study aimed to determine the mechanisms by which vascularisation of lymph node anlagen occurs during development. The structure of developing lymph nodes was studied using confocal microscopy to observe the organisation of basement membranes and the different cell types involved in the process. Expression of angiogenesis-related genes was studied using quantitative real-time PCR and microarrays. No evidence for vascularisation of the anlagen was found, though the markers used may not have stained nascent vessels. The lymph sac surrounding the anlagen was shown to exist as a two-layered structure composed of anastomosing blood and lymphatic endothelium. In vitro models of vasculogenesis and angiogenesis were developed utilising human umbilical vein endothelial cells in three dimensional collagen gels, with and without smooth muscle coverage. A spheroid-based model of angiogenesis was used to study the net angiogenic environment in developing E14.5–E17.5 anlagen, which determined that a net anti-angiogenic environment existed at all timepoints in the lymph nodes and thymus, but not skin. Additionally, tensional forces were observed to affect angiogenic sprouting in addition to soluble growth factors. As a consequence of the double-layered lymph sac observed in vitro, and the influence of anti-angiogenic factors and tensional forces observed ex vivo, a model of lymph node development involving anlagen patterning and vascularisation as a result of condensation-induced tensional forces was proposed, complementary to soluble growth factor-driven angiogenesis.

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Dias, De Campos Joana. "The pleomorphic role of stromal cells in the formation and maintenance of tertiary lymphoid organs." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6994/.

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A large body of evidence supports the role of activated stromal cells in the persistence of inflammation. The switch from resting to pathogenic stroma appears to be associated with the development of tertiary lymphoid organs (TLOs) within sites of chronic inflammation. However little is known about the immunological function of the stromal component. We utilised a murine model of inducible TLO formation in inflamed salivary glands to investigate the role of activated stromal cells characterised by the expression of gp38 and FAP during TLO development. We demonstrated that during inflammation, stroma-derived ICOSL engages ICOS on T cells, necessary for the release of lymphotoxin α and consequent TLO formation. Whilst dissecting the role of stromal cells in this context, we demonstrate that gp38 expression is required for the upregulation of adhesion molecules involved in cell clustering. Depletion of gp38+FAP+ stromal cells led to a significant reduction in lymphoid chemokine production, a decreased number of infiltrating lymphocytes and severely compromised TLO formation. Collectively, we provide evidence that activated stromal cells express FAP, provide co-stimulatory signals, and are necessary for the establishment of viral-induced TLOs, highlighting a potential novel therapeutic target in TLO-associated autoimmune diseases.

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Allouche, Farouk. "Role of RANKL in the differentiation of B cell associated stroma in secondary lymphoid organs." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ002.

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RANKL (ligand du récepteur activateur de NF-KB) est un membre de la famille des TNF dont la signalisation passe par RANK et qui joue un rôle important dans la régulation immunitaire. Chez l'adulte, RANKL est exprimé constitutivement par des cellules réticulaires marginales (MRC) des ganglions lymphatiques. Comme les MRCs sont physiquement proches des lymphocytes B (LB) et ont été proposé d’être des précurseurs de cellules dendritiques folliculaires (FDC), RANKL pourrait jouer un rôle dans la différenciation du stroma associé aux LB et dans la réponse humorale. Afin de mieux comprendre la fonction de RANKL exprimé par les MRC, nous avons généré des souris déficitaires pour RANKL dans les cellules stromales. Nous avons constaté que la formation du follicule B était perturbée ainsi que le réseau FDC. Bien que RANKL ne soit pas requis pour la formation des MRC, il est nécessaire pour l'expression de la chimiokine CXCL13 par ces mêmes cellules. Parmi les TNFRSF dont la signalisation est requise pour l’expression de CXCL13 et la différenciation des FDC, le TNFR1 était significativement réduit dans les cellules stromales des souris dépourvues de RANKL stromal. Ainsi, RANKL pourrait constituer une nouvelle cible thérapeutique contre les immunopathologies des LB en agissant sur son stroma RANKL (receptor activator of NF-κB ligand), a member of the TNF family that signals via RANK, plays an important role for immune regulation. In the adult, RANKL is constitutively expressed by marginal reticular cells (MRCs) of the lymph nodes. Because MRCs are positioned in close vicinity to B cells and may be precursors of follicular dendritic cells (FDCs), RANKL could play a role in the differentiation of B cell-associated stroma and the humoral immune response. In order to better understand the role of RANKL expressed by the MRCs, we generated mice with conditional RANKL deficiency in the stromal compartment. We found that the B cell follicle structure was disrupted and FDC network formation was reduced. Although RANKL was not required for MRC formation, it was necessary for the expression of B cell attracting chemokine CXCL13. Among the TNFRSF members known to control CXCL13 expression and FDC formation, we found that TNFR1 was significantly reduced in the RANKL cKO mice. Thus, RANKL may present a novel therapeutic strategy against B cell-mediated immunopathologies by acting on its stroma

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Ali, Hekmat M. "The histogenesis of lymphoid organs in Tilapia mossambica and antibody responses in adults and fry." Thesis, Aston University, 1987. http://publications.aston.ac.uk/14527/.

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The thymic anlagen appears in Tilapia mossambica at 2 days post hatching and becomes lymphoid at 5 days. Lymphoid cells were first seen in the pronephros at 14 days and in the spleen at approximately five weeks of age. Differentiation into red and white pulp regions was seen by 10 weeks of age. Light and electron microscopic studies of adult lymphoid organ revealed increases in size and lymphoid cell numbers. Adult thymus develops a clearer corticomedullary differentiation of thymic corpuscles in the medulla and in the splenic red and white pulp became more distinct. Melanomacrophage centres were seen in spleen and pronephros. Adult fish gave primary and secondary antibody responses following challenge with sheep red bloods cells (SRBC), Escherichia coli (E. coli) and human gamma globulin (HGG). Plaque forming cell and immunocytoadherence assays revealed that head kidney and spleen were major sites for antibody production and development of antigen reactive cells. Proliferative activity in these organs was revealed using autoradiography and scintillation counting. Increased levels of pyroninophilia were also seen following antigenic challenge. Pilot studies on adults revealed that they were capable of rejecting first and second set allografts and leucocytes from spleen and head kidney proliferated in mixed leucocyte cultures. Antibody responses to SRBC, E. coli and HGG develop at about 10-12 weeks of age. Fry given either a single injection of SRBC at 10 weeks or two injections of the same antigen at 10 weeks and 12 days later, failed to respond to a further challenge with SRBC 56 days after the first injection (A time when animals would normally respond positively to this antigen). Injection of E. coli at the same times resulted in a prolonged antibody response.

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Nardiello, Tricia Lynn. "Protease activity in lymphoid organs of BALB/C and C57BL/6 mice following murine leukemia virus /." Connect to online version, 2007. http://ada.mtholyoke.edu/setr/websrc/pdfs/www/2007/214.pdf.

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17

van, Vreden CARYN. "The role of the Secondary lymphoid organs in West Nile virus encephalitis: Immune-modifying microparticle treatment." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14729.

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West Nile virus (WNV) is a neuroinvasive flavivirus initiating an immunopathological response that causes lethal encephalitis. Recently, in a mouse model of intranasal WNV infection we showed intravenous immune-modifying microparticles (IMP) reduce CNS infiltration of Ly6Chi inflammatory monocytes by 50%, resulting in >60% survival in this lethal model. IMP+ inflammatory monocytes are sequestered by the spleen in the red pulp, with many IMP in marginal zone macrophages (MZM). Depletion of MZM with clodronate during WNV infection did not impair IMP efficacy. However, splenectomy abrogated the survival effect of IMP treatment. Importantly, splenectomised survivors showed long-term WNV immunity. Thus, by a yet undefined mechanism, the spleen, but not MZM, mediates the efficacy of IMP treatment in WNV encephalitis, but is not crucial for immunity, suggesting a role for secondary lymphoid organs in generating the adaptive immune response and contributing to immunopathology. Investigating leukocyte population dynamics in this model, we showed significant clonal expansion in the cervical lymph node, while the mesenteric and inguinal nodes had reduced T cell numbers. Our data suggest that T cells migrate to the cervical lymph nodes to contribute to the T cell effector populations generated in the adaptive immune response to CNS infection.

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Park, Hyeongdong. "Brain-body interactions in conscious experience : linking subjectivity, neural maps of visceral organs, and visual consciousness." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066055.

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Rapporter 'j'ai vu le stimulus' est la marque de la vision consciente et implique deux caractéristiques fondamentales de l'expérience consciente, à savoir son aspect qualitatif et la subjectivité. L'aspect qualitatif correspond à la perception vive du stimulus, alors que la subjectivité correspond à la conscience implicite que j'ai fait l'expérience du stimulus. Afin de déterminer les bases neurales de la subjectivité, nous introduisons le concept de cadre neural subjectif ('neural subjective frame') qui correspond aux mécanismes biologiques définissant le sujet en tant qu'une entité biologique, un point d'ancrage à partir duquel des expressions relatives à l'expérience consciente à la première personne peuvent être formulées. De plus, je propose que la représentation neurale de l'information viscérale pourrait constituer ce cadre neural subjectif. Afin de tester expérimentalement cette hypothèse, à l'aide de la magnétoencéphalographie, nous avons enregistré les réponses neuronales aux battements cardiaques, pendant que les participants réalisaient une tâche de détection visuelle. Nous avons trouvé que les réponses neuronales aux battements cardiaques avant la présentation du stimulus, dans le cortex cingulaire ventral antérieur et le lobule postérieur intrapariétal droit, pouvaient prédire la détection d'un stimulus visuel de faible contraste. Les réponses neuronales aux battements cardiaques de plus forte amplitude s'accompagnaient d'un taux de détection et d'une sensibilité plus importants, sans changement du critère de décision. Ni les fluctuations des paramètres corporels ni l'excitabilité corticale générale ne semblent contribuer à ces résultats. Par ailleurs, le fait de voir consciemment le stimulus a ralenti le battement cardiaque après la réponse des participants et cet effet de décélération cardiaque pouvait être prédit par la réponse neuronale aux battements cardiaques du cortex cingulaire antérieur ventral, avant la présentation du stimulus. Ainsi, nos résultats sont en faveur de l’hypothèse selon laquelle la cartographie des afférents viscéraux façonne notre expérience subjective perceptive. Au-delà de la vision consciente, ces résultats suggèrent que les signaux internes du corps et leurs représentations neuronales peuvent être la source de fluctuations dans des aires corticales multi-fonctionnelles Reporting “I saw the stimulus” is the hallmark of conscious vision and implies two fundamental characteristics of conscious experience, namely qualitativeness and subjectivity. Qualitativeness refers to the vivid feeling of the stimulus, whereas subjectivity refers to the implicit awareness that the experience occurred for me. To account for the neural basis of subjectivity, we introduce a concept termed the neural subjective frame which corresponds to the basic biological mechanisms defining the subject as a biological entity, as an anchoring point from which the first-person statements of conscious experience can be expressed. I further propose that neural representation of visceral information could constitute the neural subjective frame. To experimentally test this proposal, using magnetoencephalography, we recorded neural events locked to heartbeats while participants conducted visual detection task. We found that neural responses to heartbeats before stimulus onset in ventral anterior cingulate and right posterior intraparietal lobule could predict the detection of faint visual stimulus. Larger amplitude of neural responses to heartbeats were accompanied by enhanced hit-rate and sensitivity, but without changes in decision criterion. Neither fluctuations in measured bodily parameters nor in overall cortical excitability could account for this finding. In addition, consciously seeing the stimulus decelerated heartbeat after participants responded and the heartbeat slowing effect could be predicted from the prestimulus neural responses to heartbeats in ventral anterior cingulate cortex. Our findings therefore support the hypothesis that neural mapping of visceral afferents shape perceptual subjective experience. Beyond conscious vision, our findings suggest that signals from internal body and their neural representations could be sources of fluctuations in multi-functional cortical areas

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Yamanokuchi, Satoshi. "Asialo GM1 positive CD8[+] T cells induce skin allograft rejection in the absence of the secondary lymphoid organs." Kyoto University, 2006. http://hdl.handle.net/2433/143849.

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20

Navarrete, Talloni María José Constanza [Verfasser]. "Gene expression profiling of peripheral lymphoid organs in a murine model for multiple sclerosis / María José Constanza Navarrete Talloni." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/1004263953/34.

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21

VITALI, CATERINA. "Divergent roles of dendritic cells in the induction and maintenance of T cell tolerance in different secondary lymphoid organs." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2010. http://hdl.handle.net/10281/10303.

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Dendritic cells (DCs) have the capacity to initiate immune responses. Some studies postulated that in the absence of costimulation, DCs induce abortive antigen-specific T cell activation followed by T-cell deletion or unresponsiveness. To examine the peripheral conditions of antigen presentation that could lead to T cell tolerance when DCs are the exclusive APCs, we took advantage of the 2aT transgenic model. In this model, transgenic T cells (2aT cells) recognize a portion of the IgG2ab, the Bpep, in association with the MHC molecule, I-Ad. We have generated a transgenic mouse model (DC-Tg) in which the I-Ad β chain is covalently linked to the Bpep and is expressed under the control of CD11c promoter. We obtained two different groups of founders showing high or low levels of Bpep presentation (DC-Tghigh and DC-Tglow). 105 2aT cells were adoptively transferred into both groups of mice and their fate was followed. After the injection, 2aT cells underwent a robust clonal expansion and IFNg serum levels increased. Then, the primary response was controlled and 2aT cells had different fate in the two groups of recipients: in DC-Tghigh mice, they rapidly downregulated the T cell receptor (TCR); alterenatively, part of the 2aT cells transferred into DC-Tglow mice differentiated into Tregs able to suppress the T cell response. Both these phenomena occurred in the lymph nodes, while the spleens appeared not to be sites of tolerization.

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22

Munford, Nanci Derevtsoff. "Alterações histopatológicas em cães com leishmaniose visceral naturalmente infectados do município de Jequié-Ba (Brasil)." reponame:Repositório Institucional da FIOCRUZ, 2016. http://www.arca.fiocruz.br/handle/icict/16104.

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Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-10-05T18:21:34Z No. of bitstreams: 1 Nanci Derevtsoff Munford Alterações... 2016.pdf: 3140719 bytes, checksum: 5a6dfaa344823e60c8a3fa04f9a40b45 (MD5) Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-10-05T18:28:26Z (GMT) No. of bitstreams: 1 Nanci Derevtsoff Munford Alterações... 2016.pdf: 3140719 bytes, checksum: 5a6dfaa344823e60c8a3fa04f9a40b45 (MD5) Made available in DSpace on 2016-10-05T18:28:26Z (GMT). No. of bitstreams: 1 Nanci Derevtsoff Munford Alterações... 2016.pdf: 3140719 bytes, checksum: 5a6dfaa344823e60c8a3fa04f9a40b45 (MD5) Previous issue date: 2016-06-20 Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil INTRODUÇÃO: Leishmaniose visceral é uma zoonose grave que acomete uma gama de animais. O cão é considerado o principal reservatório urbano da Leishmania infantum e pode ser clinicamente assintomático ou sintomático na infecção. Poucos estudos abordam os aspectos clínicos e histopatológicos na leishmaniose visceral, sobretudo estudos sistemáticos, que fazem descrição detalhada dos achados de histopatologia e façam a correlação desses aspectos na doença. A hipótese da pesquisa é que cães naturalmente infectados com L. infantum apresentam alterações histopatológicas distintas que se relacionam com as manifestações clínicas, tendo significados diagnóstico e prognóstico. OBJETIVO: O objetivo do trabalho foi a descrição sistemática das alterações histopatológicas encontradas nos diversos órgãos de cães com leishmaniose visceral naturalmente infectados, correlacionando com diferentes manifestações clínicas. MÉTODOS: Para este estudo foram coletados amostras e dados provenientes de 58 cães do município de Jequié-Ba, área endêmica para leishmaniose. Os cães foram submetidos a exame clínico, eutanásia e coleta de material para PCR, ELISA e cultura, além de fragmentos de fígado, baço, linfonodo, pele, intestino, rins e pulmões. Os animais foram classificados em assintomáticos, quando apresentaram até dois sinais, e sintomáticos, quando exibiram mais de dois sinais. Cães com positividade simultânea nos testes de cultura esplênica, ELISA e PCR tiveram cortes dos tecidos submetidos a procedimento imunoistoquímico para avaliação da carga parasitária em linfonodo, baço e fígado. Lâminas dos fragmentos obtidos foram avaliadas sob microscopia óptica para análise das alterações. RESULTADOS: Ao todo, nove animais foram classificados como assintomáticos e 49 sintomáticos. Os 58 cães da pesquisa foram positivos em pelo menos um dos testes realizados para diagnóstico da infecção: PCR (n=91,38%), ELISA (n= 84,48%) ou cultura esplênica (n= 34,48%). No fígado, a linfocitose intrassinusoidal moderada se mostrou mais frequente no grupo dos sintomáticos (p=0,008). Nos demais parâmetros hepáticos, os grupos não obtiveram diferenças estatisticamente significantes. No baço, linfonodo, intestino, pele, rins e pulmões, as alterações se comportaram de forma semelhante entre as manifestações clínicas. A maior carga parasitária foi encontrada no baço. CONCLUSÃO: As alterações histopatológicas não mostraram diferenças entre as manifestações clínicas. INTRODUCTION: Visceral leishmaniasis is a serious zoonosis that affects a range of animals. The dog is considered the main urban reservoir of Leishmania infantum and may be clinically asymptomatic or symptomatic in infection. Few studies address the clinical and histopathological aspects in visceral leishmaniasis, especially systematic studies, which are detailed description of histopathology findings and making the correlation of these aspects of the disease. The hypothesis of the research is that dogs naturally infected with L. infantum have distinct histopathologic changes that relate to the clinical manifestations, diagnosis and prognosis. OBJECTIVE: The objective was the systematic description of histopathology found in the various organs of dogs with visceral leishmaniasis naturally infected, correlated with different clinical manifestations. METHODS: For this study were collected samples and data from 58 dogs in the city of Jequié-Ba, endemic area for leishmaniasis. The dogs underwent clinical examination, euthanasia and collection of material for PCR, ELISA and culture, as well as fragments of liver, spleen, lymph nodes, skin, intestine, kidneys and lungs. The animals were classified as asymptomatic when presented two signs, and symptomatic when exhibited more than two signals. Dogs with positive symptomatology for splenic culture, ELISA and PCR were subjected to cuts tissue immunohistochemical procedure for evaluating the parasite load in the lymph node, spleen and liver. Blades fragments obtained were evaluated by optical microscopy for analysis of changes. RESULTS: In all, nine animals were classified as asymptomatic and 49 symptomatic. The 58 dogs of the survey were positive in one of the tests for the diagnosis of infection: PCR (n = 91.38%), ELISA (n = 84.48%) or splenic culture (n = 34.48%). In the liver, moderate sinusoidal intra lymphocytosis was more frequent in the symptomatic group (p = 0.008). In other hepatic parameters, the groups no revealed statistically significant differences. In spleen, lymph nodes, intestines, skin, kidneys and lungs, the changes are similarly between the clinical manifestations. The largest parasitic load was found in the spleen. CONCLUSION: The histopathological changes showed no differences between the clinical manifestations

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23

Costa, Gerlane de Medeiros. "Estudo histomorfológico e análise dos perfis celulares do rim cefálico, fígado, baço e timo do Piaractus mesopotamicus (Holmberg, 1887, Teleósteo, Characidae), pacu." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-14022008-131838/.

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O pacu, Piaractus mesopotamicus, é um teleósteo da Família Characidae, intensivamente cultivado no Brasil por causa de sua rusticidade, crescimento rápido e fácil adaptação, além de seu excelente sabor. Para uma melhor produção de peixes, informações sobre seu sistema imunológico incluindo a histologia dos órgãos linfóides se faz necessária. Sendo assim, o objetivo deste estudo foi descrever histomorfologicamente os órgãos linfóides: rim cefálico, fígado, baço e timo do Piaractus mesopotamicus, analisando os perfis celulares de cada órgão. Foram utilizados 30 animais juvenis, com idade que variaram entre 5 meses a um ano, com peso médio de 588.1 g e comprimento total médio de 27,51 cm. Os órgãos foram pós-fixados em solução de paraformaldeído 4% e Karnovsky, depois desidratados, diafanizados em xilol e incluídos em parafina. Os cortes foram obtidos com uma espessura de 4µm e corados em hematoxilina-eosina. Os esfregaços sanguíneos foram corados em Giemsa-May Grünwald para microscopia de luz. Para microscopia eletrônica de transmissão as amostras fixadas em Karnovsky foram lavadas em sacarose e pósfixadas em tetróxido de ósmio 1%, desidratadas e emblocadas em resina Spurr. O resultado da análise macroscópica mostra que a distribuição do rim, rim cefálico, timo, fígado e baço são as mesmas encontradas na maioria dos teleósteos. Quanto à forma desses órgãos, o fígado apresentou uma variação anatômica na forma e números de lobos, sendo constituído por três lobos. O rim apresentou uma forma em \"H\", onde a região central deste se expandia sobre a bexiga natatória. O rim cefálico, em animais com idade mais avançada, se apresentou como uma dilatação na região cranial do rim, se mostrando bem visível. O timo e o baço apresentaram localização e forma similares aos de outros teleósteos. A microscopia mostrou similaridades entre os órgãos do Piaractus mesopotamicus e outros teleósteos. Na microscopia eletrônica de transmissão foram observadas similaridades ultraestruturais das células encontradas no rim cefálico, fígado, timo e baço e as já descritas em peixes teleósteos. Hemácias, trombócitos, linfócitos, eosinófilos e células granulocíticas especiais encontrados no sangue periférico, tanto de animais jovens quanto dos animais com idade mais avançada, foram os mesmos tipos celulares descritos na literatura de teleósteos. Observando nossos resultados concluímos que histologicamente os órgão linfóides de Piaractus mesopotamicus são similares aos de outros teleósteos e comparando os resultados de microscopia de transmissão concluímos que as estruturas encontradas nas nossas análises são as mesmas das descritas em outras espécies. Os resultados das nossas observações macroscópicas mostraram que o pacu é uma espécie que apresenta algumas características morfológicas singulares e que podem estar ligadas ao tipo de alimentação e a adaptações evolutivas. Esses achados demonstram que a anatomia dos órgãos de peixes e suas variações precisam ser analisados e correlacionados com suas funções e forma de vida de cada espécie. Piaractus mesopotamicus (Pacu) is a fish from the Characidae Family, it is intensively culture in Brazil because of its rusticity, easy raising and adaptation, besides its excellent flavour. In order to produce a healthy fish, information on its immunological system, including the histology of the lymphoid organs is needed. Therefore, the objective of this study is to describe histomorphologicaly the lymphoid organs: head kidney, liver, spleen and thymus of the Piaractus mesopotamicus, analyzing the cellular profiles of each organ. Thirty young animals, with age varying between 5 months to a year, with average weight and total length of 588.1 g and a 27.51 cm, respectively, were used. The organs were fixed in 4% paraformaldehyde solution, and Karnovsky, afterwards dehydrated, diafanized in xilol and included in paraffin. Four µm sections were obtained and stained with hematoxilin-eosin. Blood smears were stained with Giemsa-May Grünwald for light microscopy. Samples for transmission electric microscopy were fixed in Karnovsky, washed in sacarose and post-fixed with osmium tetroxide 1%, dehydrated and embedded in resin Spurr. The macroscopic analysis show that the localization of the kidney, head kidney, thymus, liver and spleen are very similar to most of the teleosts. Some particularities were observed in the liver, which presented an anatomical variation in the shape and number of lobes, being constituted by three lobes. The kidney presented existe \"H\" shape, where the central region overlaps the swimming bladder. The head-kidney, in adult animals, presented an evident dilation in the cranial region of the kidney. The thymus and spleen presented a similar location and shape to that of the teleosts. The light microscopy studies showed similarities between the organs of the Piaractus mesopotamicus and other teleost fishes. The transmission electron microscopy studies showed ultrastructural similarities, of the cells from the head kidney, liver, thymus and spleen with the literature. Eritrocytes, trombocytes, lymphocytes, eosinophils and special granulocytic cells were found in peripheral blood of both juvenile and adult animals and were similar to the cellular profiles described in the literature to the other teleost fishes. Our studies were successful in describing the macro, micro and ultrastructure of Piaractus mesopotamicus organs and may be used as reference for further research aiming the improvement of fish health status in aquaculture.

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Elefson, Sarah K. "DEVELOPMENTAL CHANGES IN THE PIG FROM BIRTH TO 42 DAYS POST-WEANING (1.5 – 25 KILOGRAMS BODYWEIGHT)." UKnowledge, 2019. https://uknowledge.uky.edu/animalsci_etds/112.

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This study evaluated the changes in body composition, glycogen tissue reserves, visceral organ growth, and small intestine morphology in the young pig. A total of 96 crossbred pigs were euthanized at birth (pre-suckle), days 1, 2, 3, 5, 7, 14 postpartum, weaning at day 21, and days 1, 2, 3, 5, 7, 14, 28, and 42 post-weaning. Body composition of the pig had increasing dry matter and fat, decreasing ash, calcium and phosphorus, and relatively static protein percentage over the course of the study. Liver and muscle glycogen was greatest at birth. Following birth and weaning there was a distinct decrease in the amount of liver glycogen, while there was only a clear decrease in muscle glycogen at birth. Absolute measures of the visceral organs increased in a variety of manners (linear, quadratic and/or cubic); relative measures of visceral organs responded in different manners to increasing age. In the suckling period, villous height, villous height:crypt depth ratio, and goblet cell count was greater than in the post-weaning period. Crypt depth continued to increase through the entire study. Villi measurements of the middle and distal portion of the small intestine taken via scanning electron microscope, revealed different responses to increasing age, but numerically, villi width increased, villi density, enterocyte width, and microvilli density decreased, and microvilli diameter was relatively static. Villi, on average, increased the absorptive area of the small intestine 18 fold and microvilli increased the surface area on average 400 fold. This study provided a vast amount of biometric information on the development of the young pig from birth to 42 d post weaning.

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Klosterhoff, Marta da Costa. "Desenvolvimento ontogênico do rim, timo e baço e expressão fenotípica dos receptores CD3 e CD4 em linfócitos do bijupirá Rachycentron canadum." reponame:Repositório Institucional da FURG, 2012. http://repositorio.furg.br/handle/1/2527.

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Dissertação(mestrado)- Universidade Federal do Rio Grande, Programa de Pós-Graduação em Aqüicultura, Instituto de Oceanografia, 2012. Submitted by Cristiane Silva (cristiane_gomides@hotmail.com) on 2012-08-29T19:19:57Z No. of bitstreams: 1 dissertao verso final-martaklosterhoff.pdf: 1924880 bytes, checksum: bc195444bdcc5176b1707b88f00b25c1 (MD5) Approved for entry into archive by Bruna Vieira(bruninha_vieira@ibest.com.br) on 2012-09-18T03:14:20Z (GMT) No. of bitstreams: 1 dissertao verso final-martaklosterhoff.pdf: 1924880 bytes, checksum: bc195444bdcc5176b1707b88f00b25c1 (MD5) Made available in DSpace on 2012-09-18T03:14:20Z (GMT). No. of bitstreams: 1 dissertao verso final-martaklosterhoff.pdf: 1924880 bytes, checksum: bc195444bdcc5176b1707b88f00b25c1 (MD5) Previous issue date: 2012 O bijupirá Rachycentron canadum, apresenta várias características favoráveis para a aquicultura, como alta taxa de crescimento, bons coeficientes de eficiência alimentar e carne de excelente qualidade, entre outras. No presente estudo foi realizada uma análise do sistema imune do bijupirá através de técnicas de histologia e imunohistoquímica. A ontogenia dos órgãos imunocompetentes (rim anterior, timo e baço) em larvas e juvenis de bijupirá, desde a eclosão até 53 dias após a eclosão (dae), foi realizada através da análise histológica. O rim foi o primeiro órgão linfohematopoiético a aparecer, presente no 1º dia após eclosão (dae) (3,8 ± 0,04mm), o surgimento do baço foi no 5º dae (4,8 ± 0,2mm) e no 7º dae (5,4 ± 0,2 mm) o timo; conforme análise os órgãos linfóides tornaram-se evidente com o avanço da idade do peixe. Foi possível também estabelecer a presença de receptores específicos de linfócitos através da imunomarcação com anticorpo monoclonal anti-CD3 e anti-CD4. Foi encontrado no timo os primeiros receptores linfocitários CD3 ao 7º dae com 27% mm² e 99% mm² de tecido tímico aos 53 dae (154 ± 4,6mm). A expressão fenotípica dos receptores CD3 no rim foi destacada no 8º dae (6,5 ± 0,1mm) com uma expressão de 10% mm² e 32% mm² de tecido renal aos 53 dae. A imunomarcação dos receptores linfocitários CD4 foi destacada inicialmente no timo com 7 dae, com 5% mm² e aos 53 dae com 63% mm² de linfócitos imunomarcados com anti-CD4. No Rim, a população de linfócitos T4 foi registrada primeiramente aos 13º dae (12,4 ± 0,7 mm) com 9% mm² e aos 53 dae com 28% mm² da população linfocitária CD4 do tecido renal, definindo o desenvolvimento funcional do sistema específico, associada a capacidade da memória imunológica. Também foi possível estabelecer que ocorre uma repovoação de linfócitos T no rim anterior, os linfócitos que migram do rim anterior para o timo e adquirem receptores específicos de células T, retornando ao rim anterior e mantendo suas atividades imunes. O estudo dos mecanismos do sistema imune são importantes para o sucesso de um cultivo, pois as doenças são uma das principais causas de perdas econômicas na aquicultura em todo mundo. The cobia Rachycentron canadum has several desirable traits for aquaculture, most importantly a rapid growth rate, good feed conversion ratio and good flesh quality. In the present study, the immune system of cobia was evaluated through histology and immunohistochemistry. Ontogeny of immunocompetent organs (head kidney, thymus and spleen) in cobia larvae and juveniles from hatching to 53 days after hatching (dah) was histologically described. The first lymphohematopoietic organ to appear was the kidney, at 1 dah (3.8 ± 0.04 mm), followed by the spleen at 5 dah (4.8 ± 0.2 mm) and the thymus at 7 dah (5.4 ± 0.2 mm); the lymphoid organs became evident as the fish grew older. It was also possible to establish the presence of specific lymphocyte receptors through immunolabeling with the monoclonal antibodies anti-CD3 and anti-CD4. The first evidence of CD3 lymphocyte receptors was found at 7 dah with 27% mm² of thymic tissue and at 8 dah (6.5 ± 0.1 mm) in the kidney, expressed in 10% of the kidney tissue. Initially, 5% mm2 of lymphocytes with CD4 lymphocyte receptors were initially immunolabeled in the thymus. In the kidney, T4 lymphocyte population was registered to be present at 13 dah (12.4 ± 0.7 mm) with 9% mm², defining the functional development of the specific system, associated to immunological memory capacity It was also possible to establish a repopulation of T lymphocytes in the head kidney; lymphocytes migrate from the head kidney to the thymus and acquire specific T-cell receptors, returning to the head kidney and maintaining their immune activities. The knowledge about the immune system mechanisms is important for farming activities, as diseases are the major causes of economic losses in global aquaculture.

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Roubanis, Aristeidis. "Investigating the metabolism of regulatory T cells in non-lymphoid tissues using a genetic approach and an in vivo adaptation of SCENITH." Electronic Thesis or Diss., Sorbonne université, 2024. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2024SORUS321.pdf.

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La régulation du métabolisme cellulaire est un élément central gouvernant le destin et la fonction des cellules T. Parmi les cellules T, les cellules T régulatrices CD4+ Foxp3+ (Tregs) sont essentielles pour le maintien de la tolérance au soi et de l'homéostasie immunitaire. Les Tregs sont présentes dans les tissus lymphoïdes où elles contrôlent les réponses immunitaires et dans divers tissus non-lymphoïdes où elles maintiennent l'homéostasie tissulaire. Les précurseurs des Tregs colonisant les tissus non-lymphoïdes sont présents dans la rate et les ganglions lymphatiques et subissent des étapes de différenciation développementale. Cependant, les mécanismes par lesquels les Tregs colonisent les tissus non-lymphoïdes et comment les Tregs tissulaires s'adaptent métaboliquement aux différents microenvironnements tissulaires restent mal compris en partie à cause des difficultés expérimentales à évaluer les profils métaboliques de cellules rares dans des conditions physiologiques. Pour étudier le métabolisme des Tregs, des souris knock-out conditionnelles pour le point de contrôle métabolique Liver kinase B1 (LKB1) (cKO) ont été générées. Ces souris ont une durée de vie significativement réduite en raison d'un trouble hyperinflammatoire systémique, malgré un nombre relativement normal de Tregs dans la rate et les ganglions lymphatiques. LKB1, principalement connu pour activer AMPK et moduler le métabolisme mitochondrial, semble crucial pour la colonisation des tissus non-lymphoïdes par les Tregs. Une analyse plus approfondie a révélé l'absence des précurseurs des Tregs tissulaires matures dans la rate des souris cKO, suggérant un blocage de la différenciation des Tregs tissulaires en l'absence de LKB1.Des avancées récentes, telles que la technique SCENITH, permettent d'étudier le métabolisme des cellules rares en mesurant la traduction des protéines comme indicateur de la consommation d'énergie par cytométrie en flux. Cependant, cette technique nécessite traditionnellement que les cellules soient cultivées ex vivo ou in vitro, ce qui peut altérer leur métabolisme. Pour résoudre ce problème, une méthode innovante dérivée de SCENITH a été mise en œuvre pour investiguer le métabolisme cellulaire des cellules T dans la rate et les poumons à l'état stationnaire. Comparée à la SCENITH classique, cette nouvelle technique aide également à améliorer la viabilité des cellules, en particulier pour les Tregs. Les résultats obtenus avec la SCENITH in vivo ont révélé que les cellules T conventionnelles et les Tregs partagent des profils métaboliques similaires dans la rate et les poumons. Notamment, le métabolisme des cellules T pulmonaires repose principalement sur la phosphorylation oxydative à l'état stationnaire, tandis que les cellules T spléniques utilisent également la glycolyse. De plus, le maintien de l'expression de Foxp3 dans les Tregs est influencé par les inhibiteurs métaboliques affectant la traduction des protéines et la disponibilité énergétique. Nos résultats soulignent le rôle de LKB1 dans la différenciation et la colonisation des Tregs tissulaires et mettent en avant l'importance de l'adaptation métabolique dans la différenciation des Tregs tissulaires. La nouvelle technique SCENITH in vivo pourrait fournir des informations précieuses pour évaluer l'état métabolique des cellules T rares dans leurs environnements naturels Regulation of cellular metabolism is a central element governing the fate and function of T cells. Among T cells, CD4+ Foxp3+ regulatory T cells (Tregs) are critical for the maintenance of self-tolerance and immune homeostasis. Tregs are present in lymphoid tissues where they control immune responses and in various non-lymphoid tissues where they maintain tissue homeostasis. Precursors of Tregs colonising non- lymphoid tissues are present in the spleen and lymph nodes and undergo developmental differentiation steps. However, the mechanisms by which Tregs colonise non-lymphoid tissues and how tissue Tregs metabolically adapt to varying microenvironments across tissues remain poorly understood partly because of experimental difficulties in assessing the metabolic profiles of rare cells in physiological conditions. To investigate the metabolism of Tregs, mice conditionally knocked out for the metabolic checkpoint Liver kinase B1 (LKB1) (cKO) were generated. These mice have a significantly reduced lifespan due to a systemic hyperinflammatory disorder, despite having relatively normal numbers of Tregs in the spleen and lymph nodes. LKB1, primarily known for activating AMPK and modulating mitochondrial metabolism, appears crucial for the colonisation of NLT by Tregs. Further analysis revealed the absence of the mature tissue Treg precursors in the spleen of cKO mice, suggesting a block of tissue Treg differentiation in the absence of LKB1.Recent advances, such as the SCENITH technique, allow the study of the metabolism of rare cells by measuring protein translation as an indicator of energy consumption by flow cytometry. However, this technique traditionally requires cells to be cultured ex vivo or in vitro, which can alter their metabolism. To address this issue, an innovative method derived from SCENITH was implemented to investigate the cellular metabolism of T cells in the spleen and lungs at steady state. Compared to classical SCENITH, this new technique also helps improve cell viability, in particular for Tregs. Results obtained with the in vivo SCENITH revealed that conventional T cells and Tregs share similar metabolic profiles in the spleen and lungs. Notably, lung T cell metabolism relies mainly on oxidative phosphorylation at steady state, while spleen T cells also utilise glycolysis. Additionally, maintaining Foxp3 expression in Tregs is influenced by metabolic inhibitors affecting protein translation and energy availability. Our findings highlight the role of LKB1 in the differentiation and colonisation of tissue Tregs and underscore the importance of metabolic adaptation in tissue Treg differentiation. The new in vivo SCENITH technique may provide valuable insights to assess the metabolic status of rare T cells in their natural environments

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Yang, Liqun. "Characterization of the Physiologic Function of NF-κB2 p100". University of Toledo Health Science Campus / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=mco1263334529.

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Hörnblad, Andreas. "Imaging the pancreas : new aspects on lobular development and adult constitution." Doctoral thesis, Umeå universitet, Umeå centrum för molekylär medicin (UCMM), 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-50601.

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The mouse pancreas is a mixed exocrine and endocrine glandconsisting of three lobular compartments: the splenic, duodenal and gastric lobes. During embryogenesis, the pancreas forms from two progenitor populations located on the dorsal and ventral side of the primitive gut tube. These anlagen are brought in close proximity as the gut elongates and rotates, and fuse to form a single organ. The splenic and duodenal lobes develop from the dorsal and ventral anlagen, respectively. In the adult pancreas, exocrine tissue secretes digestive enzymes intothe gut lumen to support nutrient uptake. The endocrine Islets of Langerhans are scattered throughout the exocrine tissue and aid in regulation of energy homeostasis through the secretion of hormones. One of the key players in energy homeostasis is the pancreatic ß-cell, which is the most abundant cell type of the islets. The β-cells regulates blood glucose levels through the action of insulin. Conditions where this regulation does not function properly are gathered under the common name of Diabetes mellitus. Type 1 diabetes (T1D) is characterized by insulin deficiency due to autoimmune destruction of the ß-cells. Using recently developed protocols for optical projection tomography (OPT) whole-organ imaging, we have revealed new spatial and quantitative aspects on ß-cell mass dynamics and immune infiltration during the course of T1D development in the non-obese diabetic (NOD) mouse model. We show that although immune infiltration appears to occur asynchronously throughout the organ, smaller islets, mainly located in the periphery of the organ, preferentially loose their ß-cells during early stages of disease progression. Larger islets appear more resistant to the autoimmune attack and our data indicate the existence of a compensatory proliferative capacity within these islets. We also report the appearance of structures resembling tertiary lymphoid organs (TLOs) in association with the remaining islets during later phases of T1D progression. OPT has already proven to be a useful tool for assessments of ß-cellmass in the adult mouse pancreas. However, as with other techniques, previous protocols have relied on a tedious degree of manual postivacquisition editing. To further refine OPT-based assessment of pancreatic ß-cell mass distribution in the murine pancreas, we implemented a computational statistical approach, Contrast-Limited Adaptive Histogram Normalisation (CLAHE), to the OPT projection data of pancreata from C57Bl/6 mice. This methodology provided increased islet detection sensitivity, improved islet morphology and diminished subjectivity in thresholding for reconstruction and quantification. Using this approach, we could report a substantially higher number of islets than previously described for this strain and provide evidence of significant differences in islet mass distribution between the pancreatic lobes. The gastric lobe stood out in particular and contained a 75% higher islet density as compared to the splenic lobe. Although the development of the early pancreatic buds has been relatively well studied, later morphogenetic events are less clear and information regarding the formation of the gastric lobe has largely been missing. Using OPT we have generated a quantitative three-dimensional road map of pancreatic morphogenesis in the mouse. We show that the gastric lobe forms as a perpendicular outgrowth fromthe stem of the dorsal pancreas at around embryonic day (e) 13.5, which grows into a mesenchymal domain overlaying the pyloric sphincter and proximal part of the glandular stomach. By analyzing mutant mice with aberrant spleen development, we further demonstrate that proper formation of the gastric lobe is dependent on the initial formation of the closely positioned spleen, indicating a close interplay between pancreatic and splenic mesenchyme during development. Additionally, we show that the expression profile of markers for pancreatic multipotent progenitors within the pancreas is heterogenous with regards to lobular origin. Altogether, our studies regarding the morphogenesis and adult constitution of the mouse pancreas recognize lobular heterogeneities that add important information for future interpretations of this organ.

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Audemard-Verger, Alexandra. "Caractérisation des lymphocytes T résidents des organes lymphoïdes secondaires à l’état basal." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB260/document.

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Une résidence à long terme de lymphocytes T (LTs) au sein de la plupart des tissus non lymphoïdes a été récemment décrite, notamment à la suite d’infections. Ces cellules confèreraient à l’hôte une meilleure protection en cas de réinfection. À l'aide de deux approches expérimentales différentes, l'injection d'anticorps bloquant l’entrée des LTs dans les ganglions lymphatiques (LNs) et la génération de parabioses par chirurgie, nous avons pu mettre en évidence, à l’état basal, la résidence d’une proportion significative des LTs αβ mémoires CD4+, des LTs αβ régulateurs CD4+ et d’une sous-population des LTs γδ dans les organes lymphoïdes secondaires. Les LTs CD4+ régulateurs et mémoires résidents ont en commun de nombreuses caractéristiques phénotypiques et fonctionnelles, et partagent avec leurs homologues issus de tissus non lymphoïdes une signature transcriptionnelle commune de résidence. Les LTs γδ résidents, quant à eux, arborent des caractéristiques phénotypiques et fonctionnelles proches de celles des cellules du système immunitaire inné. Si le microbiote semble jouer un rôle important dans la résidence des LTs αβ CD4+ des plaques de Peyer (PPs), son rôle ne semble pas être prépondérant dans la résidence de ces cellules au sein des LNs. Comme dans de nombreux tissus non lymphoïdes, la sous-expression de S1PR1 pourrait en partie expliquer la résidence des LTs αβ CD4+. Par contre, les LTs γδ seraient, eux, retenus dans les tissus lymphoïdes de par des interactions étroites avec les macrophages. Enfin, la résidence des LTs αβ augmente avec l'âge au point que la majorité des LTs CD4+ régulateurs et mémoires des LNs et des PPs sont en fait résidents chez des souris âgées. Nos résultats montrent que la résidence des cellules T n'est pas seulement une caractéristique des tissus non lymphoïdes mais qu’elle peut être étendue aux organes lymphoïdes secondaires. Le rôle respectif de ces différentes populations de LTs devra être exploré In the last decade, numerous data have demonstrated the existence of T cells residing in non-lymphoid tissues, mostly after infectious diseases. These resident memory T cells may represent a first line of defense against pathogens at front-line sites of microbial exposure upon reinfection. Using two different experimental approaches such as the injection of integrin-neutralizing antibodies that inhibits the entry of circulating lymphocytes into lymph nodes and long-term parabiosis experiments, we have highlighted the long-term residence of a substantial proportion of regulatory and memory CD4 αβ T cells and γδ T cells within the secondary lymphoid organs of specific pathogen free mice. Resident γδ T cells display innate-like characteristics. Lymph node-resident regulatory and memory CD4 αβ T cells share many phenotypic and functional characteristics, including a core transcriptional profile, with their cell-counterparts from non-lymphoid tissues. Microbiota plays an important role in αβ T-cell residence in Peyer’s patches but only a small one if any in lymph nodes. Like in many non-lymphoid tissues, S1PR1 down-regulation may account forαβ T-cell residency within secondary lymphoid organs although other mechanisms may account for this especially in the case of lymph node memory CD4 T cells. Specific in vivo cell-depletion strategies have allowed us to demonstrate that macrophages are the main actors involved in the long-term retention of γδ T cells in secondary lymphoid organs. Strikingly, T-cell residence increases with age to the point that the majority of regulatory and memory CD4 αβ T cells from LNs and Peyer’s patches are in fact resident T cells in old mice. Altogether, our results show that T-cell residence is not only a hallmark of non-lymphoid tissues but can be extended to secondary lymphoid organs

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Winter, Susann. "Funktionale Bedeutung der homöostatischen Chemokinrezeptoren CCR7 und CXCR5 im Verlauf von mukosalen Immunantworten." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16328.

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Die kontinuierliche Rezirkulation von Immunzellen durch periphere und sekundäre lymphatische Organe (SLOs) ist Bestandteil der Immunüberwachung und wichtig für die Aufrechterhaltung und Funktionsbereitschaft des Immunsystems. Der homöostatische Chemokinrezeptor CCR7 vermittelt dabei nicht nur die Rezirkulation von Lymphozyten durch SLOs, sondern scheint auch an der homöostatischen Rezirkulation von Lymphozyten durch nicht-lymphoide periphere Gewebe beteiligt zu sein. Im Rahmen dieser Arbeit wurde mithilfe von CCR7-defizienten Mäusen die funktionale Bedeutung von CCR7 für die homöostatische Rezirkulation von Lymphozyten durch das Peritoneum untersucht und nachgewiesen, dass CCR7 der dominante Chemokinrezeptor ist, der unter physiologischen Bedingungen die Transitzeit von Lymphozyten durch das Peritoneum festlegt. Die gestörte Rezirkulation von Lymphozyten begünstigte außerdem die Entstehung von tertiären lymphoiden Organen (TLOs) in der Magenschleimhaut von CCR7-defizienten Mäusen. Untersuchungen zur zellulären und molekularen Grundlage dieser und weiterer pathomorphologischer Veränderungen in der Magenschleimhaut von CCR7-defizienten Mäusen verdeutlichten die Funktion von CCR7 für die Etablierung von zentraler und peripherer Toleranz gegenüber gastrischen Antigenen. Fehlt CCR7, dann entwickelten Mäuse eine spontane Autoimmungastritis, welche durch gastritogene CD4+ T-Zellen verursacht wurde, deren Aktivierung auch unabhängig von Lymphknoten und TLOs erfolgte. Die Entstehung von TLOs wird auch bei einer durch Helicobacter pylori ausgelösten chronischen Gastritis beobachtet. Die Expression des homöostatischen Chemokinrezeptors CXCR5 und seines Liganden CXCL13 ist mit der Entwicklung dieser TLOs korreliert worden. Unter Verwendung eines Mausmodells für H. pylori-induzierte chronische Gastritis konnte gezeigt werden, dass CXCR5 die Ausbildung von TLOs vermittelt und eine Rolle für die Induktion von H. pylori-spezifischen T-Zell- sowie humoralen Immunantworten spielt. Homeostatic recirculation of immune cells through peripheral and secondary lympoid organs (SLOs) is required for immune surveillance and the maintenance and functionality of the immune system. The homeostatic chemokine receptor CCR7 controls not only lymphoid cell trafficking to and within SLOs, but also seems to be involved in the homeostatic recirculation of lymphocytes through non-lymphoid peripheral tissues. Within the scope of this work we investigated the functional relevance of CCR7 for the homeostatic recirculation of lymphocytes through the peritoneal cavity and could show, that CCR7 is the dominant chemokine receptor which defines the transit time of lymphocytes in the peritoneal cavity under physiological conditions. Impaired recirculation of lymphocytes also promoted the development of tertiary lymphoid organs (TLOs) in the gastric mucosa of CCR7-deficient mice. Analysis of the cellular and molecular mechanisms underlying these and other pathomorphological alterations in the gastric mucosa of CCR7-deficient mice provided further evidence regarding the function of CCR7 for the establishment of central and peripheral tolerance towards gastric antigens. Mice that lack CCR7 spontaneously developed autoimmune gastritis, which was caused by gastritogenic CD4+ T-cells. Such autoreactive T cell responses were also initiated in the absence of lymph nodes and TLOs in CCR7/LT-alpha double-deficient mice. Development of TLOs is also observed during chronic gastritis induced by Helicobacter pylori. The expression of the homeostatic chemokine receptor CXCR5 and its ligand CXCL13 has been correlated with the development of these TLOs. Using a mouse model for H. pylori-induced chronic gastritis, we could show that CXCR5 is responsible for the development of TLOs and also plays a role for the induction of H. pylori-specific T and B cell responses.

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Mensen, Angela. "Funktionelle Charakterisierung der Chemokinrezeptoren CXCR7 und CCR7 in der Pathogenese lymphatischer Erkrankungen." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16391.

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Die Expression homöostatischer Chemokinrezeptoren auf hämatopoetischen Neoplasien wird zunehmend mit tumorpathogenen Funktionen in Zusammenhang gebracht. In der Arbeit wurden Funktionen der Rezeptoren CXCR7 und CCR7 in der Pathogenese lymphatischer Erkrankungen anhand von Mausmodellen charakterisiert. Für CXCR7 konnte in der normalen Differenzierung von T-Zellen eine schwache Expression in murinen Thymozyten, dagegen eine verstärkte, vor allem intrazellulär lokalisierte Expression in peripheren aktivierten T-Zellen identifiziert werden. Eine aberrante Überexpression lag in humanen Zelllinien, aber auch in primären Fällen von T-ALL und klassischen Hodgkin-Lymphomen vor. Die Analyse eines retroviralen Überexpressionsmodells ergab für CXCR7 die Funktion als anti-apoptotischer Kostimulator während der thymischen beta-Selektion. Im Signaltransduktionskomplex mit CXCR4 und dem präTCR vermittelte CXCR7 einen effizienteren DN3-zu-DN4 Übergang. Unreife Thymozyten waren durch eine verstärkte Apoptoseresistenz und Expression von anti-apoptotischen Bcl2-Molekülen charakterisiert. Dies könnte CXCR7 überexprimierende Thymozyten putativ empfänglicher für die Entwicklung von T-ALLs machen. Für CCR7 konnten in der Arbeit bedeutende Funktionen in der organspezifischen Dissemination von B-Zelllymphomen identifiziert werden. Unter Verwendung des Eµ-Myc-Mausmodells wurde gezeigt, dass Eµ-Myc Lymphomzellen CCR7-abhängig in die T-Zellzone von Milz und Lymphknoten einwandern und dort durch reziproke Interaktionen mit gp38+ FRCs und DCs entscheidende Überlebenfaktoren, darunter Ihh, Igf-1 und VCAM-1, erhalten. Die Lymphomzellen vermittelten darüber hinaus eine aktive Veränderung der Stromazellzusammensetzung, welche durch ein expandiertes FRC-Netzwerk, durch die Induktion putativ immunsupprimierender DCs und durch ein inflammatorisches Milieu charakterisiert war. Eine Inhibition der Lymphom-Stroma-Interaktionen könnte daher eine neue Strategie der Lymphomtherapie darstellen. In recent years the expression of homeostatic chemokine receptors on hematological tumors was increasingly associated with tumor pathogenic functions. Within this thesis, functions of the chemokine receptors CXCR7 und CCR7 in the pathogenesis of lymphoid diseases were characterized using different mouse models. For CXCR7, low expression levels were detected in murine thymocytes during normal T cell development. Enhanced expression was found mainly intracellularly in peripheral activated T cells. An aberrant overexpression was identified in human cell lines and primary cases of T-ALL and classical Hodgkin lymphoma. The analysis of a retroviral overexpression model suggested a function of CXCR7 as an anti-apoptotic costimulator during thymic beta-selection. In a functional complex with CXCR4 and the preTCR CXCR7 mediated a more efficient DN3-to-DN4 transition. CXCR7 expressing thymocytes were characterized by enhanced apoptosis resistance and expression of anti-apoptotic Bcl2-family genes. Thus, CXCR7 could putatively make immature thymocytes more susceptible to develop T-ALL. In addition, new insights into the function of CCR7 in the context B cell lymphoma dissemination were gained within this thesis. Applying the Eµ-Myc mouse model, CCR7 was shown to mediate the specific homing of Eµ-Myc lymphoma cells into the T cell zone of spleen and lymph nodes. Here, lymphoma cells received pivotal survival signals following reciprocal interactions with gp38+ FRCs and DCs, amongst them Ihh, Igf-1 and VCAM-1. Moreover, the lymphoma cells induced a survival promoting active remodelling of the T cell zone stroma, which was characterized by the expansion of the FRC network, by the induction of putatively immune suppressive DCs and by the induction of a pro-inflammatory milieu. Therefore, an inhibition of lymphoma-stroma interactions could provide a new strategy in lymphoma therapy.

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Fletcher, Carrie-Anne St Vincent's Clinical School UNSW. "The role of secondary lymphoid organs in baff induced autoimmune disease." 2007. http://handle.unsw.edu.au/1959.4/40867.

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Systemic lupus erythematosus (SLE) and Sj?gren?s syndrome (SS) are both heterogeneous autoimmune diseases with strong B cell aspects. A proportion of SLE and SS patients exhibit elevated serum BAFF (B cell activating factor of the TNF family); BAFF plays a key role in B cell homeostasis, survival and tolerance. BAFF transgenic (Tg) mice develop nephritis and salivary gland destruction that resemble aspects of SLE and SS respectively. Autoimmune disease development in BAFF Tg mice correlates with marginal zone (MZ) B cell expansion and the abnormal presence of MZ-like B cells outside of the spleen. The role of MZ B cells in BAFF induced autoimmune disease was analysed by crossing BAFF Tg mice with Lymphotoxin-β knockout mice (creating LTβ-BTg mice) which lack most peripheral lymph nodes, and also lack MZ B cells as a result of disrupted splenic architecture. LTβ-BTg mice were not protected against nephritis but exhibited reduced salivary gland infiltration and destruction. Indicating that the development of sialadenitis but not nephritis in BAFF Tg mice is MZ B cell dependent. Nephritis development in LTβ-BTg mice was associated with the detection of B-1 B cells in the inflamed kidneys. As B-1a B cell survival is dependent on the spleen, the contribution of B-1a B cells to nephritis development in BAFF Tg mice was assessed by crossing BAFF Tg mice to congenitally asplenic Hox11-/- mice (creating Hox11 -BTg mice). The absence of a spleen and B-1a B cells in Hox11-BTg mice delayed the nephritis development. In contrast, splenectomy of BAFF Tg mice at 12 weeks of age did not alter nephritis onset. In these mice B-1a B cells persisted in the peritoneal cavity and MZ-like B cells were detected in the periphery 8 months after surgery. In summary, nephritis development in BAFF Tg mice is unaltered by the absence of MZ B cells, but delayed in the absence of a spleen, MZ and B-1a B cells. Thus, B-1a and B-1b B cells may be potential targets for the treatment of nephritis in SLE patients with elevated BAFF.

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Antão, Ana Isabel Vieira. "In vitro infection of lymphoid tissues by HIV-2." Master's thesis, 2016. http://hdl.handle.net/10451/28421.

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Tese de mestrado, Ciências Biofarmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2016 Lymphoid organs constitute an optimal environment for the defense against the invasion of pathogens by promoting immune responses. They are the major reservoirs of human immunodeficiency virus (HIV) infection, however their infection has only been focused in the context of HIV-1. HIV-2 represents a more attenuated form of HIV disease, characterized by slower CD4+ T cell decline and progression to AIDS, that doesn’t have the same impact worldwide as HIV-1. Nevertheless, HIV-2 constitutes a unique naturally occurring model of attenuated HIV disease valuable for the study of HIV pathogenesis. Understanding the impact of HIV-2 infection on lymphoid organs will provide new insights regarding the ability of the tissue to promote immune responses. Here we investigated the impact of HIV-2 in human tonsillar tissue, a secondary lymphoid organ (SLO). Tonsil organ cultures (TOCs) were infected with HIV-2 or HIV-1 primary isolates using either CCR5 (R5) or CXCR4 (X4) coreceptors. All viruses were able to replicate in the tissue, as revealed by immunohistochemistry. In addition, we found that HIV-2-infected lymphocytes from TOCs presented similar levels of total HIV DNA as HIV-1. Surprisingly, Gag mRNA and protein levels were significantly higher in tissue infection by HIV-1 X4 as compared to R5-tropic HIV-1 or HIV-2, suggesting that the viral production observed in TOCs may be due to the infection of other cells in the tissue, and that viral transcriptional regulation may be altered in X4-tropic HIV-2. Interestingly, despite the lower lymphocyte-associated viral replication observed with X4-tropic HIV-2, the impact on the viability of CD4+ T cells and on the memory CD4+ T cell compartment was similar to that observed with HIV-1 X4. Moreover, we found that infection of TOCs with X4-tropic viruses resulted in a higher frequency of cells expressing Foxp3, a molecule related with the regulatory phenotype. This was particularly observed for X4-tropic HIV-2 infection and was not related with cell proliferation. In addition, we observed a significantly higher depletion of follicular cells within Foxp3+ cells in TOCs infected with X4-tropic HIV-2, indicating higher persistence of Foxp3+ Tregs. Finally, we observed that all viruses were able to deplete the T follicular helper (TFH) subset, a subset that is essential for B cell differentiation. In conclusion, our data showed that HIV-2 is able to infect lymphoid tissue in a coreceptor-dependent manner, but that the replication cycle was impaired in lymphocytes at the transcriptional level. These findings on in vitro infection of lymphoid tissues by HIV-2 will provide new insights regarding HIV immunopathogenesis. Os órgãos linfóides proporcionam respostas imunitárias contra patogénios e é onde estão a maior parte dos linfócitos existentes no corpo humano. Estes órgãos são os maiores reservatórios da infeção pelos vírus de imunodeficiência humano (VIH), no entanto o impacto da infeção é maioritariamente estudado no contexto do VIH-1. O VIH- 2 representa uma forma atenuada da doença, caracterizada pela lenta diminuição de linfócitos CD4+ e progressão para SIDA. Para além disso, o impacto na sociedade é muito menor que o do VIH-1. Contudo, o VIH-2 é um modelo único de ocorrência natural valioso para o estudo da patogénese do VIH. Por esta razão, compreender o impacto da infeção por VIH-2 em órgãos linfóides poderá levar a novas descobertas relativas à habilidade destes tecidos proporcionar respostas imunitárias. Neste projeto, investigámos o impacto do VIH-2 em tecido de amígdala humana, um órgão linfóide secundário. Culturas de amígdala foram infetadas com isolados primários de VIH-1 ou VIH-2 que usam ou o corecetor CCR5 (R5) ou o CXCR4 (X4). Demonstrámos que ambos os vírus são eficientes a infetar o tecido, tendo sido evidenciado por imunohistoquímica. Para além disso, demonstrámos que os linfócitos derivados da cultura de amígdala infetados por VIH-2 tinham uma quantidade de ADN viral integrado semelhante ao das infetadas por VIH-1. Surpreendentemente, a quantidade de mRNA e proteína Gag produzidos mostrou ser significativamente mais elevada na infeção do tecido pelo VIH-1 X4 comparativamente ao VIH-1 R5 e ao VIH-2, sugerindo que o vírus observado no tecido poderá estar relacionado com infeção de outras células, e que a transcrição do vírus X4 HIV-2 poderá estar alterada. No entanto, apesar da baixa replicação associada aos linfócitos observada no tecido infetado por VIH-2 X4, o impacto na viabilidade de linfócitos T CD4+ e no compartimento de linfócitos T CD4+ memória foi semelhante ao observado com o VIH-1 X4. No entanto, a infeção pelos vírus que usam o coreceptor CXCR4 resultou no aumento da expressão de Foxp3 nas células dos tecidos, uma molécula associada ao fenótipo regulador, e tal não se deveu a um aumento da proliferação destas células. Observámos ainda que o VIH-2 X4 depletou significativamente as células Foxp3+ foliculares, persistindo preferencialmente linfócitos T reguladores Foxp3+. Por último, observámos uma depleção dos linfócitos T foliculares por parte de todos os vírus. Em conclusão, os nossos dados mostram que o VIH-2 é capaz de infetar o tecido dependentemente do corecetor, mas o ciclo de replicação foi diminuído nos linfócitos a um nível transcricional. Estes resultados relativos à infeção de órgãos linfóides in vitro por VIH-2 permitirão novas descobertas sobre a imunopatogénese do VIH.

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Wu, Chun-Shiu, and 吳淳繡. "Zebrafish Cdx1b regulates left-right asymmetry in the brain and visceral organs by modulating Nodal signaling." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/5v46au.

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博士 國立臺灣大學 生化科學研究所 105 Left-right asymmetric patterning is important for proper development of visceral organs and neurogenesis that is dependent on the appropriate activity of Nodal signaling. In zebrafish, after breaking the left-right symmetry by nodal flow inside Kupffer''s vesicle (KV), ndr3 (Nodal-related 3) is asymmetrically expressed in the left lateral plate mesoderm (LPM) and turns on downstream genes encoding the Nodal ligands (ndr2 and ndr3 itself), the antagonists of Nodal ligands (lft1 and lft2), and the downstream effector of Nodal signaling (pitx2). This Self-Enhancement and Laterality Inhibition system of Nodal signaling are considered as a conserved molecular cascade across species to control their temporal and spatial expression precisely. Zebrafish caudal-related homeobox 1b (cdx1b) belongs to the caudal type homeobox (cdx) gene family, which has been implicated in anterior-posterior axial patterning and intestinal development across diverse bilaterians. Previous studies have shown that zebrafish Cdx1b regulates early endoderm formation and differentiation of various intestinal cell lineages. In this thesis, a new role of Cdx1b in left-right asymmetrical patterning was discovered. Knockdown of cdx1b by specific antisense morpholino oligonucleotides (MOs) caused the loss of left-laterality in the epithalamus, the failure of heart looping, and isomerism or situs inversus of visceral organs. In the cdx1b-knockdown embryos (cdx1b morphants), left-sided expression of Nodal signaling genes (ndr3, lft1, lft2, and pitx2c)were altered in the LPM, and expressions of ndr2, lft1 and pitx2c were not detected in the left dorsal diencephalon during the late somite and early pharygula stages (18-26 hpf). During the early- somite stages (4-6 somite stages), the cilia of KV were shortened and the Nodal flow was weakened in the cdx1b morphants. The symmetric right-sided expression of charon (the antagonist of Nodal around KV) was also altered in the cdx1b morphants. Knockdown of cdx1b reduced the expression of ndr2, lft1, and pitx2c in the prechordal plate and the anterior ventral neuroectoderm at the bud stage. In addition, decreased expression of gsc, a downstream target of Nodal signaling in the prechordal plate and ventral neuroectoderm, and shh, a structure marker of these tissues, were observed in the cdx1b morphants. These results indicate that Cdx1b is important for patterning of the Nodal-induced anterior mesendoderm and the anterior ventral neuroectoderm. Based on motif predictions by the JASPAR and UCSC websites, chromatin immunoprecipitation results showed that Cdx1b can bind on the conserved promotor/enhancer region of ndr2 (chr12:49,427,858-49,428,038) and lft1 (chr20:35,102,628-35,102,818). Together, these results suggest that Cdx1b may regulate transcription of ndr2 and lft1 to maintain proper activity of Nodal signaling that is essential for the mesendoderm induction, the anterior neurulation and subsequent establishment of laterality of epithalamus in the zebrafish embryo.

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JIAN, SHIN-YUNG, and 簡欣永. "Automatic measurement of adipose tissue inside visceral cavity and organs using MRI and visible human data." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/94926722047881734505.

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碩士 中原大學 電機工程研究所 98 This thesis hopes to present a convenient way to calculate the magnetic resonance imaging of intra-abdominal fat area and liver fat area and fat area of the spine, so that doctors can more easily make the diagnosis, and can save medical human resources, do not let doctors waste time in visceral fat rendering work. Magnetic resonance imaging of this paper is from the diaphragm to the pelvic floor. Which contains three different PROTOCOL, liver, abdomen and pelvis. The thesis of seven patients about each data contains 70 images. In this thesis, morphology, histogram equalization and the POWELL algorithm and other methods, supplemented by visible human data for each image to calculate an area of intra-abdominal fat, liver fat, and spine fat. The results and the error rate using the correct statistics, the accuracy and sensitivity shown by three parameters. This paper uses histogram equalization and morphological patterns and other methods supported by the successful development of a convenient can be calculated within the human abdominal adipose tissue magnetic resonance imaging, with an average error of 24.4%, in the future may be able to assist doctors to diagnose the intra-abdominal fat on cardiovascular disease or help to the study.

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Lin, Chun-Ming, and 林俊明. "Characterization of porcine circovirus type 2 infection in immune cells and lymphoid organs by using in vitro and in vivo models." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/24526321160918095898.

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博士 國立臺灣大學 獸醫學研究所 100 Porcine circovirus type 2 (PCV2) is a small, non-enveloped, single-stranded, circular DNA virus, and the infection of PCV2 is distributed in swine population worldwide. Experimental and field studies indicate that PCV2 is a required but insufficient causative agent of postweaning multisystemic wasting syndrome (PMWS), a disease that has a significant impact on swine production. The characteristic feature of PMWS is the presence of high levels of PCV2 antigens and nucleic acid in the lymphoid system along with variable lymphoid depletion and granulomatous inflammation. Until now, the precise mechanism regarding the replication of PCV2 in immune cells and the pathogenesis of PMWS are remained to be elucidated. Therefore, serial in vitro (Chapters II and III) and in vivo (Chapters IV, V and VI) models were performed in the present study to clarify above issues. In the first portion of the present study, it is hypothesized that immune activation induces PCV2 replication in activated lymphocytes. Therefore, concanavalin A (Con A)-stimulated peripheral blood lymphocytes (PBLs) was used as an in vitro model to clarify the susceptibility of swine lymphocytes to PCV2 (Chapter II). Subsequently, this model was further expanded by the addition of monocyte-derived dendritic cells (MoDCs) and recombinant cytokines, including interleukin 2 (IL-2), IL-4, and interferon γ, to determine the correlations between lymphocyte activation and PCV2 replication (Chapter III). The evidences of increase in cellular PCV2 antigen- and/or nucleic acid-containing rates, PCV2 genome copy number, and titer of infectious PCV2 in mitogen-stimulated, PCV2-infected PBLs support that PCV2 infects and replicates in activated swine lymphocytes. By phenotyping the PCV2 antigen-positive cells, it was revealed that T and B lymphocytes as well as monocytes were susceptible to PCV2 infection; however, IgM-positive B lymphocytes appeared to have a relatively higher PCV2-positive rate (Chapter II). While lymphocytic cells served as a major site of PCV2 replication, MoDCs harbored a significant amount of PCV2 antigens but did not actively sustain the replication of PCV2. Further study has demonstrated that IL-2 and the accessory cell function of DCs were key factors required for cell proliferation and PCV2 replication in PCV2-infected lymphocytes (Chapter III). In the second portion of the present study, serials in vivo studies were conducted to characterize the changes in inguinal LNs in the naturally PCV2-infected pigs (Chapters IV and V) and to infer the possible mechanism of PCV2-associated lymphoid lesion developed (Chapter V and VI). It is speculated that limited by their sensitivity, conventional in situ hybridization (ISH) and/or immunohistochemical (IHC) staining may not be sufficient to detect few copies of PCV2 contained in a portion of immune cells. Therefore, a more sensitive method, indirect in situ polymerase chain reaction PCR (ISPCR), was developed through the combination of PCR and ISH procedure (Chapter IV). Using the indirect ISPCR, signals of PCV2 nucleic acid, especially those in germinal centers, could be more effectively detected. In addition, a detailed grading system was proposed to categorize the pattern of natural PCV2 infection in lymphoid follicles (Chapter IV) and used as criteria for sample selection in the following studies (Chapters V and IV). To obtain tissue-based information effectively, a new model of high-throughput tissue microarray (TMA) in conjunction with semi-quantified ISH/IHC staining and statistic analysis was established (Chapter V). The results of multiple regression analysis showed that each of PCV2, porcine respiratory and reproductive syndrome virus (PRRSV), and porcine parvovirus (PPV) had its own contributions on the development of lymphoid lesions in PMWS with PCV2 as the major causative agent. B lymphocyte depletion and macrophage proliferation and infiltration are the two hallmarks of PCV2-associated lymphoid lesions. Apart from blood recruitment, local T cell and macrophage proliferation may play a crucial role on the development of granulomatous inflammation (Chapter V). Furthermore, the expressions of 92 selected immune genes in 7 and 35 inguinal LNs obtained from healthy subclinically PCV2-infected and PMWS-affected pigs were assessed by the integration of several quantitative reverse transcription polymerase chain reaction experiments (Chapter IV). Using hierarchical cluster analysis, the gene expression profiles in these PCV2-infected LNs were generally compatible with the divergent functions of different immune cell populations. Aberrant immune activation and imbalanced Th1/Th2 orientation are considered to contribute to the development of PCV2 infection-associated lymphoid lesions. Principle component analysis of the expression profile of the 92 selected immune genes in the 42 above mentioned LNs revealed that 52.23% of the total data variants could be explained by the top-3 principle components, suggesting that the disease development of PCV2 infection may be associated with a few major and some minor factors (Chapter VI). In conclusion, evidences from the present study suggest that lymphocytes are indeed susceptible to PCV2 (Chapters II, III and IV). Immune activation modulated by DCs and cytokines triggers the replication of PCV2 in lymphocytes (Chapter III). Subsequently, the perturbation of immune regulation by PCV2 facilitates the co-infection of other pathogens. Due to the persistent or repeated episodes of antigenic stimulation, the balance between immune suppression and activation is further perturbed (Chapter VI). As the progression of PMWS development, lymphoid depletion and granulomatous inflammation occur in the LNs bearing heavy PCV2 load (Chapter V).

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Cheng, Shu-Yun, and 鄭淑云. "Studies on the growth of lymphoid organs in cobia and molecular cloning of the lipopolysaccharide biosynthesis regulator protein gene of Photobacterium damselae subspecies piscicida." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/99579121286794596579.

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碩士 國立屏東科技大學 獸醫學系 92 Cobia Rachycentron canadum (Linnaeus) culture offers great possibilities in aquaculture, because of its fast growth rate and its commercial interest. Recently farmers are facing problems in cobia culture due to disease outbreak and cause mass mortalities in cage cultured juvenile cobia, especially cobia photobacteriosis (junior synonym pseudotuberculosis or pasteurellosis). The photobacteriosis pathogen is Photobacterium damselae subsp. piscicida, have 50 to 60﹪mortalities in cobia. This study presents basic data on the growth of the lymphoid organs (include head kidney, spleen and thymus) in cobia, from 1 to 8 months. The growth and cellular composition of the kidney, spleen and thymus were detected in cobia. The age showed a higher imperfect correlation to body fork than body weight (γ=0.9961 and γ=0.9073). All lymphoid organ weight showed a higher imperfect correlation to body weight than they did to age and body fork (γ=0.9995, γ=0.9993 and γ=0.9968). In the other hand, all organs grew as the fish grew, but they attainted their maximum relative weights (expressed as a percentage of body weight) at 2-3 months of age. The total number of leucocytes in the lymphoid organ tissue, and per gram of tissue per gram of fish, decreased with age. The blood picture showed no obvious fluctuations with age. Lysozyme activity of all lymphoid organ and serum from 3-8 months of age, results showed no significant different (p＞0.05). Lipopolysaccharides (LPS, endotoxin) are associated with the cell walls of Gram-negative bacteria, often play a important virulence factor in bacterial pathogenicity. So, studies on molecular cloning of the LPS biosynthesis regulator protein gene of P. damselae subsp. piscicida by using E. coli expression system and pRSET vector, expect it could be potential used as a candidate antigen for development of subunit vaccine against P. damselae subsp. piscicida in the near future. The purified expressed recombinant fusion protein was abtained by using 6×His affinity column and was strongly reactive to rabbit-P. damselae subsp. piscicida ECP-antibody by using Western blotting assay in terms of antigenicity.

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