Thèses : « Intestinal Health and Immunity »

1

Pascoal, Leonardo Augusto Fonseca [UNESP]. « Fontes de fibra para leitões recém desmamados ». Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/104920.

Texte intégral

Résumé :

Made available in DSpace on 2014-06-11T19:33:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-10-19Bitstream added on 2014-06-13T18:45:23Z : No. of bitstreams: 1 pascoal_laf_dr_jabo.pdf: 4325049 bytes, checksum: f0c924e1bbe52682097d3edf19366f63 (MD5)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Com o objetivo de avaliar os efeitos das inclusões de celulose purificada, casca de soja e polpa cítrica, como fontes de fibra nas dietas para leitões desmamados, foram realizados 4 ensaios. No ensaio I determinou-se as digestibilidades dos nutrientes e da energia das fontes de fibra e no II, as digestibilidades das dietas contendo esses ingredientes, utilizando-se o método de coleta total de fezes. No ensaio III avaliou-se o desempenho, o tempo de trânsito, a incidência de diarréia e a imunidade humoral e no IV, as características morfofisiológicas e microbiológicas do sistema digestório. As dietas experimentais utilizadas nos ensaios II, III e IV foram: DC - dieta controle — composta principalmente por milho, farelo de soja e fonte de lactose; CEL - dieta composta principalmente por milho, farelo de soja, fonte de lactose e 1,5% de celulose purificada; CS - dieta composta principalmente por milho, farelo de soja, fonte de lactose e 3% de casca de soja e PC - dieta composta principalmente por milho, farelo de soja, fonte de lactose e 9% de polpa cítrica. Utilizou-se o delineamento em blocos casualizados, para controlar diferenças no peso inicial. Com base nos resultados do ensaio I, verifica-se que a polpa cítrica apresenta melhor valor nutricional, e que as fontes de fibra podem ser utilizadas com o objetivo de modular a microbiota intestinal. Nos ensaios II e III, observa-se que as inclusões de celulose purificada, casca de soja e polpa cítrica, como fontes de fibra nas dietas de leitões desmamados, nä° afetam a digestibilidade da maioria dos nutrientes e da energia, o desempenho e o tempo de trânsito das dietas no trato gastrintestinal. Entretanto, a utilização de celulose purificada promove efeito benéfico no controle da diarréia e melhora alguns parâmetros imunológicos. No ensaio IV, nota-se que a adição de fontes de fibras solúveis, como casca de soja e...
A total of 4 assays were conducted to evaluate the effect of purified cellulose, soybean hulls and citrus pulp as fiber sources in diets for weaned pigs. In assay 1 it was determined the nutrient and energy digestibilities for each source of fiber. At assay 2 it was determined the digestibilities of diets added by fibrous ingredients using total feces collection method. In assay 3 It was evaluated the performance, transit time, diarrhea incidence and humoral immunity and in assay 4 the morphophysiological and microbiological characteristics of digestive tract. The experimental diets used in the assays 2, 3 and 4 were: DC — control diet, based on corn, soybean meal and lactose source; CEL — diet based on corn, soybean meal, lactose source and 1,5% of purified cellulose; CS — diet based on corn, soybean meal, lactose source and 3% of soybean hulls; PC — diet based on corn, soybean meal, lactose source and 9% of citrus pulp. It was used a randomized block a design according to control the differences of body weight of piglets. The results of assay I citrus pulp has higher nutritional values and than those fiber sources can be used to modulate intestinal microbiota. According to results of assays II and III, purified cellulose, soybean hulls and citrus pulp as fiber sources in diets for weaned pigs do not affect nutrients and energy digestibility, performance and gastrointestinal transit time. The use of purified cellulose can reduce diarrhea incidence and promotes better results in some immunological parameters. According to assay IV, the result indicates that soluble fiber sources, as soybean hulls and citrus pulp, promote a modification on morphophysiology and microbiology of tract, suggesting an adaptation on digestive system of weaned pigs by the presence of the fiber in diets

Styles APA, Harvard, Vancouver, ISO, etc.

2

Pascoal, Leonardo Augusto Fonseca. « Fontes de fibra para leitões recém desmamados / ». Jaboticabal : [s.n.], 2009. http://hdl.handle.net/11449/104920.

Texte intégral

Résumé :

Resumo: Com o objetivo de avaliar os efeitos das inclusões de celulose purificada, casca de soja e polpa cítrica, como fontes de fibra nas dietas para leitões desmamados, foram realizados 4 ensaios. No ensaio I determinou-se as digestibilidades dos nutrientes e da energia das fontes de fibra e no II, as digestibilidades das dietas contendo esses ingredientes, utilizando-se o método de coleta total de fezes. No ensaio III avaliou-se o desempenho, o tempo de trânsito, a incidência de diarréia e a imunidade humoral e no IV, as características morfofisiológicas e microbiológicas do sistema digestório. As dietas experimentais utilizadas nos ensaios II, III e IV foram: DC - dieta controle - composta principalmente por milho, farelo de soja e fonte de lactose; CEL - dieta composta principalmente por milho, farelo de soja, fonte de lactose e 1,5% de celulose purificada; CS - dieta composta principalmente por milho, farelo de soja, fonte de lactose e 3% de casca de soja e PC - dieta composta principalmente por milho, farelo de soja, fonte de lactose e 9% de polpa cítrica. Utilizou-se o delineamento em blocos casualizados, para controlar diferenças no peso inicial. Com base nos resultados do ensaio I, verifica-se que a polpa cítrica apresenta melhor valor nutricional, e que as fontes de fibra podem ser utilizadas com o objetivo de modular a microbiota intestinal. Nos ensaios II e III, observa-se que as inclusões de celulose purificada, casca de soja e polpa cítrica, como fontes de fibra nas dietas de leitões desmamados, nä° afetam a digestibilidade da maioria dos nutrientes e da energia, o desempenho e o tempo de trânsito das dietas no trato gastrintestinal. Entretanto, a utilização de celulose purificada promove efeito benéfico no controle da diarréia e melhora alguns parâmetros imunológicos. No ensaio IV, nota-se que a adição de fontes de fibras solúveis, como casca de soja e ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: A total of 4 assays were conducted to evaluate the effect of purified cellulose, soybean hulls and citrus pulp as fiber sources in diets for weaned pigs. In assay 1 it was determined the nutrient and energy digestibilities for each source of fiber. At assay 2 it was determined the digestibilities of diets added by fibrous ingredients using total feces collection method. In assay 3 It was evaluated the performance, transit time, diarrhea incidence and humoral immunity and in assay 4 the morphophysiological and microbiological characteristics of digestive tract. The experimental diets used in the assays 2, 3 and 4 were: DC - control diet, based on corn, soybean meal and lactose source; CEL - diet based on corn, soybean meal, lactose source and 1,5% of purified cellulose; CS - diet based on corn, soybean meal, lactose source and 3% of soybean hulls; PC - diet based on corn, soybean meal, lactose source and 9% of citrus pulp. It was used a randomized block a design according to control the differences of body weight of piglets. The results of assay I citrus pulp has higher nutritional values and than those fiber sources can be used to modulate intestinal microbiota. According to results of assays II and III, purified cellulose, soybean hulls and citrus pulp as fiber sources in diets for weaned pigs do not affect nutrients and energy digestibility, performance and gastrointestinal transit time. The use of purified cellulose can reduce diarrhea incidence and promotes better results in some immunological parameters. According to assay IV, the result indicates that soluble fiber sources, as soybean hulls and citrus pulp, promote a modification on morphophysiology and microbiology of tract, suggesting an adaptation on digestive system of weaned pigs by the presence of the fiber in diets
Orientador: Maria Cristina Thomaz
Coorientador: Jane Maria Bertocco Ezequiel
Banca: Jacinta Diva Ferrugem Gomes
Banca: Fábio Enrique Lemos Budiño
Banca: Nilva Kazue Sakomura
Banca: Otto Mack Junqueira
Doutor

Styles APA, Harvard, Vancouver, ISO, etc.

3

Lowe, Patrick P. « Inebriated Immunity : Alcohol Affects Innate Immune Signaling in the Gut-Liver-Brain Axis ». eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/987.

Texte intégral

Résumé :

Alcohol is a commonly consumed beverage, a drug of abuse and an important molecule affecting nearly every organ-system in the body. This project seeks to investigate the interplay between alcohol’s effects on critical organ-systems making up gut-liver-brain axis. Alcohol initially interacts with the gastrointestinal tract. Our research describes the alterations seen in intestinal microbiota following alcohol consumption in an acute-on-chronic model of alcoholic hepatitis and indicates that reducing intestinal bacteria using antibiotics protects from alcohol-induced intestinal cytokine expression, alcoholic liver disease and from inflammation in the brain. Alcohol-induced liver injury can occur due to direct hepatocyte metabolic dysregulation and from leakage of bacterial products from the intestine that initiates an immune response. Here, we will highlight the importance of this immune response, focusing on the role of infiltrating immune cells in human patients with alcoholic hepatitis and alcoholic cirrhosis. Using a small molecule inhibitor of CCR2/CCR5 chemokine receptor signaling in mice, we can protect the liver from damage and alcohol-induced inflammation. In the brain, we observe that chronic alcohol leads to the infiltration of macrophages in a region-specific manner. CCR2/CCR5 inhibition reduced macrophage infiltration, alcohol-induced inflammation and microglial changes. We also report that chronic alcohol shifts excitatory/inhibitory synapses in the hippocampus, possibly through complement-mediated remodeling. Finally, we show that anti-inflammasome inhibitors altered behavior by reducing alcohol consumption in female mice. Together, these data advance our understanding of the gut-liver-brain axis in alcoholism and suggest novel avenues of therapeutic intervention to inhibit organ pathology associated with alcohol consumption and reduce drinking.

Styles APA, Harvard, Vancouver, ISO, etc.

4

Al-Dahwi, Zaineb. « Impairment of protective immunity to intestinal helminthiases ». To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2007. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

5

Roach, Tamara I. A. « Immunity to Trichuris muris in the mouse ». Thesis, University of Nottingham, 1986. http://eprints.nottingham.ac.uk/12886/.

Texte intégral

Résumé :

Quantitative and qualitative analyses of the serum antibody responses of NIH, C57BL/10, BALB/c, DBA/2 and CFLP mice infected with Trichuris muris have been made using ELISA and immunoprecipitation techniques. No correlation was found between specific serum antibody titres measured using T. muris E/S products and the time of onset of expulsion in the different mouse strains examined. However, there were some differences in the antigen recognition profiles of some sera as determined by immunoprecipitation analyses. In all the strains of mice examined significant increases in detectable specific serum antibody to the parasite E/S products occurred around day 15 to 20 postinfection and continued to rise, as measured up to at least day 40 and even up to day 65. Cortisone acetate treatment during larval development, in infected CFLP mice, in order to establish heavy adult worm burdens, did not reduce specific antibody titres to T. muris E/S products. In responding and tolerant DBA/2 mice there was no marked difference in either the kinetics of specific serum antibody production during primary and secondary infections, or in the antigen specificities of secondary infection sera. The "defect" in mechanism in the tolerant DBA/2 mice, which allows primary infections of T. muris to develop to patency, was shown to be permanent as secondary infections with the parasite could also establish in these animals. An investigation was made of the phenomenon of tolerance in the DBA/2 model- system and in the cortisone treated CBA mice. The capacity of MLNC from different groups of animals to produce IL-2 in vitro upon mitogen stimulation was investigated, on the basis that IL-2 deficit during antigen presentation may result in immune tolerance. Although no differences were found in the responding and tolerant DBA/2 cell-Vpopulations, there was an apparently synergistic interaction between cortisone administration and T. muris infection which dramatically reduced the IL-2 producing capacity of the MLNC. However, IL-2 cannot yet be ruled out as a factor in the inherent tolerance of a proportion of the DBA/2 population as IL-2 receptor expression by the 2 groups of cells assayed was not examined. Basic analyses of the antigens of T. muris were performed. The major protein of adult male homogenate (AMA) was also the major protein of the excretory/secretory (E/S) products and the surface antigen preparations. In addition several common E/S and surface antigens were shown to have proteolytic enzyme activities against gelatin and/or casein. The relationship between T. muris and Trichinella spiralis was examined in greater detail, and the m. wts. of the cross-reacting antigens were determined. Evidence suggested that the stichosomes of these worms may be the source of these antigens. Both Trichuris muris adults and Trichinella spiralis infective larvae each had common major E/S and surface antigens, indeed, both were shown to have surface proteases. These studies were extended to examine the possibility of cross-reactivity between Trichuris muris and T. trichiura; mouse infection sera and human infection sera respectively were able to cross-react with heterologous antigen preparations. The demonstration that anti-Trichinella spiralis 48 kD and 50/55 kD stichocyte antigen MoAbs also reacted with Trichuris trichiura adult homogenate in ELISA supports the suggestion that common stichocyte antigens may exist amongst the trichuroid nematodes Trichuris muris, Trichuris trichiura and Trichinella spiralis. Monoclonal antibodies were produced against the E/S products of Trichuris muris, which were characterized in terms of isotype and antigen specificities. Initial experiments indicated that one of the IgA MoAbs recognizing 34,22,20 and 18 kD E/S proteins may be effective in the passive transfer of immunity.

Styles APA, Harvard, Vancouver, ISO, etc.

6

Brady, Jessica. « Protection and stimulation of intestinal innate immunity using mannan oligosaccharides ». Taylor & ; Francis, 2010. http://hdl.handle.net/1993/4774.

Texte intégral

Résumé :

Necrotic enteritis (NE) caused by Clostridium perfringens is a re-emerging disease of economic importance in areas of the world where antibiotic growth promoters have been banned. Various alternatives to antibiotic growth promoters are being tested including prebiotics known as mannan oligosaccharides (MOS) which have been shown to mitigate the effects of NE and potentially boost the immune system, though the mechanism is not completely understood. The objective of this study is to test the effectiveness of MOS on balance of microbial populations, gut morphology and immune system ability; specifically: C. perfringens genetic populations, villi architecture and TLR2 and TLR4 activity. This study focuses on organic broiler chickens fed MOS at 0, 2, 4, 6 and 8g/kg feed and challenged with an inoculation of C. perfringens isolated from an outbreak on a local organic farm. Toxinotype and 16S phylogenetic analysis of C. perfringens were reviewed as well as feed efficiency, gut morphology and gene expression of Toll Like Receptors 2 and TLR4 using qRT-PCR. All field isolates were found to be Type A C. perfringens, as were most experimental isolates except for two isolates taken pre-innoculation, which were more likely attributed to contamination of the experiment room by cattle which were housed there previously. No association between pathogenecity and toxin genes cpb2 or netB could be established during this study. 16S analysis found all C. perfringens isolates to be highly related, though there seemed to be a change in populations post inoculation which did match the field isolate used for inoculation. Gut morphology readings including villi height, width and area, crypt depth and lymphocyte and goblet cell concentrations showed some significant effect though it was not in a common area of the intestine and was often due to the interaction between treatments and time. These results also failed to reproduce effects found by other authors. TLR2 and 4 were not found to be significantly different between treatments, though certain trends were noted. The lack of significant treatment effects as well as the low reproducibility of these outcomes leads to the conclusion that, though MOS may contribute to gut health and maturity based on these and conclusions found by other authors, its effect is hinging on other factors such as management and nutrition.

Styles APA, Harvard, Vancouver, ISO, etc.

7

Sallam, Jamal A. « Intestinal humoral immunity in man : IgA and anti-salmonella antibodies ». Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20766.

Texte intégral

Résumé :

Studies of gut immunity must be carried out on intestinal fluid and jejunal biopsies. Recent work from Edinburgh has shown that the use of Whole Gut Lavage (WGL) technique is a non-invasive, direct and reliable method of obtaining intestinal fluids. My thesis describes the use of WGL technique in a variety of studies on gastro-intestinal mucosal immunity. The effect of the newly licensed oral live typhoid vaccine Ty21a on gut immunity was investigated in a group of 22 healthy British volunteers. Later on, the intestinal immune responses to naturally acquired Salmonella infection were investigated in a group of patients who had had the infection within the preceding 12 months. Results obtained in these studies were compared with results obtained from healthy individuals, patients with inflammatory bowel disease (IBD) and African children from Sierra Leone. I investigated further the effect of heavy smoking and non-smoking in healthy volunteers on gut immunity and the effect of administration of the live oral vaccine Ty21a on the intestinal mucosal immune responses of smokers and non-smokers. I also studied agglutinating antibodies in WGL fluids and sera. Patients with a variety of GI diseases and patients who had had Salmonella infection were tested against a panel of 11 Salmonella antigens using a modified Widal test in microtitration plates. In the course of the above studies, I found that there were patients who had very low or absent intestinal IgA but had normal levels of IgA in the serum. Therefore, I investigated further this phenomenon by counting plasma cells in the lamina propria of intestinal biopsies from patients with "intestinal IgA deficiency" and normal controls using image analysis.

Styles APA, Harvard, Vancouver, ISO, etc.

8

Srinivasan, N. « The role of inflammasomes in intestinal inflammation ». Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:04ad577c-a8dd-46eb-811a-79a3980ff806.

Texte intégral

Résumé :

Single Nucleotide Polymorphisms (SNPs) in the intracellular pattern recognition receptor gene NLRP3 are associated with susceptibility to Crohn’s disease, a form of inflammatory bowel disease (IBD). Following cell damage or infection, NLRP3 triggers the formation of inflammasomes, a multimolecular protein complex containing NLRP3, ASC and caspase-1, which mediate secretion of IL-1β and IL-18. NLRP3 inflammasome activation in macrophages has been implicated in protection against several pathogens, but whether NLRP3 activation in tissue cells contributes to protective immunity against bacterial pathogens is unknown. We show that upon infection with the attaching/effacing (A/E) intestinal pathogen Citrobacter rodentium, Nlrp3-/- and Asc-/- mice displayed higher bacterial colonization, more weight loss and exacerbated intestinal inflammation. We further show that Nlrp3 inflammasome activation in intestinal epithelial cells (IECs) acts rapidly after infection to limit bacterial replication and penetration, and inhibits the development of inflammatory pathology in the gut. We also show that epithelial Nlrp3-mediated protection is independent of the classical inflammasome cytokines IL-1β and IL-18. Thus an Nlrp3-Asc circuit in IECs regulates early defense against a mucosal pathogen and limits inflammation in the intestine. Nlrp3 inflammasome activation has also been implicated in protection in acute models of experimental colitis, but its role in chronic models of colitis is unknown. We found that Asc signaling is necessary for the development of innate chronic intestinal inflammation driven by Helicobacter hepaticus. Thus while deficient inflammasome signaling in tissue cells increases susceptibility towards enteric pathogens, excessive inflammasome activation can drive chronic intestinal inflammation.

Styles APA, Harvard, Vancouver, ISO, etc.

9

Graham, Suzanne. « Intestinal immunity and pathology in animal models of type 1 diabetes ». Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402005.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

10

Bains, Manpreet. « Genetic Disruption of VIP Signaling Alters Intestinal Microbial Structure and Immunity ». Diss., North Dakota State University, 2018. https://hdl.handle.net/10365/28788.

Texte intégral

Résumé :

Vasoactive intestinal peptide (VIP) regulates clock gene expression in the brain that synchronizes diurnal feeding behaviors in mammals. In the gastrointestinal (GI) tissues, VIP influences host nutrient absorption from ingested food, and regulates host metabolic functions. VIP signaling ensures efficient nutrient absorption by influencing ghrelin and leptin expression to balance caloric intake. Importantly, obese humans have elevated plasma VIP levels, supporting its association with fat mass accumulation. In contrast, VIP deficiency leads to weight loss and reduced adiposity, while disrupting epithelial cell nutrient absorption, tight junctions and mucus secretion. Moreover, VIP regulates host glucose metabolism as VIP knockout mice are pre-diabetic with elevated blood glucose and insulin levels. In addition to metabolism, VIP is anti-inflammatory and when knocked out results in exacerbated inflammatory bowel disease (IBD) pathology. The GI track is also home to ?40 trillion bacteria, called the gut microbiota, which unlock additional calories from fiber for the host. Microbiota dysbiosis is caused by dysfunction in biological systems downstream from VIP signaling, including dysregulated expression of host clock genes, metabolic hormones, immune-relevant mediators and metabolic and inflammatory disease states, like obesity and IBD. It is not known, however, whether the VIP signaling axis contributes to the maintenance of the gut microbiota structure and diversity. We hypothesized that VIP deficiency will cause gut dysbiosis, lower bacterial diversity and reduce its energy extraction potential. To this end, we isolated fecal samples from VIP knockout mice (VIP-/-) and employed 16S rRNA sequencing. VIP deficiency (VIP-/- and VIP-/+) resulted in marked gut microbial compositional changes and reduced bacterial diversity compared to male and female VIP+/+ littermates (n=48). Increased abundance of Bacteroides, Parabacteroides and Helicobacter genera (gram-negative, GN), with reductions of Lachnospiraceae NK4A136, Oscillibacter and Ruminiclostridium genera (gram-positive, GP), were the driving force for the observed increase in the GN/GP ratio. A predicted algorithm program, called PICRUSt, showed changes in microbial metabolism consistent with elevated lipopolysaccharide metabolism and reduced intake of fiber in VIP-/- mice. These data support that VIP regulates intestinal homeostasis by maintaining microbiota balance, diversity and energy harvesting potential, while upholding an anti-inflammatory tone by limiting lipopolysaccharide biosynthesis.

Styles APA, Harvard, Vancouver, ISO, etc.

11

Bours, Martijn Jan Leo. « Role of extracellular ATP in immunity and intestinal defence effects on intestinal permeability and enterocyte-driven inflammatory response / ». Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Universiteit Maastricht [host], 2007. http://arno.unimaas.nl/show.cgi?fid=9328.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

12

Lenoir, Loïc. « Effet protecteur des polyphénols de la verveine odorante dans un modèle d'inflammation colique chez le rat ». Phd thesis, Université d'Auvergne - Clermont-Ferrand I, 2011. http://tel.archives-ouvertes.fr/tel-00719693.

Texte intégral

Résumé :

La consommation de polyphénols, micronutriments largement répandus dans lesaliments d'origine végétale, a été associée à la diminution du risque de développement denombreuses pathologies telles que maladies cardiovasculaires, maladies neurodégénérativesou cancers. Cet effet des polyphénols s'explique en partie par leurs propriétés antioxydanteset anti-inflammatoires. Du fait de leur faible absorption au niveau de l'intestin grêle, lespolyphénols sont présents en grande quantité dans le côlon où ils peuvent exercer cespropriétés. L'inflammation intestinale fait interagir le système immunitaire intestinal avecde nombreux facteurs environnementaux et est fréquemment associée à une augmentationdu stress oxydant via la production d'espèces réactives de l'oxygène par les cellulesimmunitaires. De nombreuses études ont montré, sur des modèles animaux d'inflammationintestinale, les effets protecteurs de certains polyphénols. La verveine odorante (Aloysiatriphylla (L'Hérit.) Britton) est une plante médicinale connue pour ses vertus thérapeutiquesdigestives et anti-spasmodiques et couramment consommée en infusion. L'infusé deverveine odorante contient de grandes quantités de polyphénols (acides phénoliquescomplexes et dérivés de flavones) et ses propriétés antioxydantes ont été mises en évidenceaussi bien in vitro qu'in vivo.L'objectif de cette thèse a donc été d'évaluer l'effet d'une consommation préventived'un infusé de verveine odorante à dose nutritionnelle (40 g/l et 4 g/l) sur le développementd'une inflammation intestinale modérée chez le rat. Des rats Wistar ont consommé commeboisson l'infusé de verveine seul pendant deux semaines puis associé à un agentinflammatoire, le sulfate de dextran sodique (DSS), à 4% pendant 7 ou 9 jours. L'effet de laverveine a été évalué sur différents paramètres cliniques (diarrhée, saignements rectaux,poids corporel), marqueurs de l'inflammation (longueur du côlon, score histologique,activité myéloperoxydase, cytokines) et du stress oxydant (peroxydation lipidique,glutathion, défenses antioxydantes enzymatiques). Les cellules immunitaires ont étéidentifiées dans le sang ainsi que dans les structures lymphoïdes secondaires par cytométrieen flux. Enfin l'étude du métabolisme des polyphénols en situation inflammatoire ou non aété initiée par l'analyse de l'excrétion urinaire des dérivés polyphénoliques.Lors d'une inflammation de 7 jours, la consommation préventive d'infusé deverveine à 40 g/l et 4 g/l retarde l'apparition de diarrhée et de saignements rectaux, limite larétraction du côlon et la diminution de la prise de poids des rats. Malgré l'absence d'effetsur l'activité myéloperoxydase, l'infusé à 40 g/l atténue les altérations histologiques de lamuqueuse colique induites par l'inflammation. L'infusé à 4 g/l stimule l'activité de lasuperoxyde dismutase et réduit la peroxydation lipidique. Les deux infusés modulent lespopulations de cellules immunitaires dans les structures lymphoïdes secondaires (ganglionsmésentériques et plaques de Peyer), en particulier les lymphocytes B et les lymphocytes Tcytotoxiques. L'excrétion urinaire des polyphénols de la verveine est faible et n'est pasaffectée par l'inflammation. Lors d'une inflammation de 9 jours, les deux infusés limitentl'augmentation d'activité de la myéloperoxydase. Seul l'infusé à 40 g/l limite la rétractiondu côlon, stimule l'activité de la glutathion réductase et diminue les taux d'IL-6 et deTNF-α. Ainsi, nous avons montré qu'une consommation préventive d'un infusé de verveineodorante offre des effets protecteurs lors de l'inflammation intestinale en agissant àdifférents niveaux. L'exploration des voies de signalisation impliquées pourrait permettre demieux comprendre les effets protecteurs de cette boisson de consommation courante.

Styles APA, Harvard, Vancouver, ISO, etc.

13

Harrison, Oliver J. « The role of IL-18 in intestinal immune regulation ». Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:adcd849b-6a08-4ba9-b7db-0743a29cb377.

Texte intégral

Résumé :

Elevated levels of the cytokine interleukin-18 (IL-18) are found in many chronic inflammatory disorders, including inflammatory bowel disease (IBD). However, the role of IL-18 in mucosal immunity and inflammation is not well understood. At mucosal and environmental interfaces, Th17 cells have been shown to contribute to protection from pathogenic infection. In contrast, regulatory T (Treg) cells maintain intestinal homeostasis by preventing aberrant inflammatory responses to the resident microbiota. We demonstrate that under homeostatic conditions, colonic Th17 cells highly express IL-18 receptor (IL-18R1) and that intestinal epithelial cell production of IL-18 acts directly on CD4⁺ T cells to limit colonic Th17 differentiation. Furthermore, whilst IL-18R1-signalling is dispensable for induction of colitis, we observed a critical role for IL-18R1-signalling in Foxp3⁺ Treg mediated control of colitis. Together, these studies demonstrate that the intestinal epithelium regulates colonic CD4⁺ T cell responses through production of the cytokine IL-18.

Styles APA, Harvard, Vancouver, ISO, etc.

14

Harvey, Joanna E. « T cell and macrophage differentiation markers in the normal and inflamed human intestine ». Thesis, University of Southampton, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236511.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

15

Echeverry, Andrea. « Innate and Adaptive Immunity in Murine Neonates Infected with the Intestinal Pathogen Yersinia enterocolitica ». Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/480.

Texte intégral

Résumé :

Neonates are generally thought to be more likely to suffer from gastrointestinal disease, owing in part to diminished immune cell function. To gain insight into the development of mucosal immune responses during early life, we developed a model of orogastric infection with the Gram-negative bacterium Yersinia enterocolitica using murine neonates. Remarkably, neonatal mice of either the BALB/c or C57BL/6 mouse strains showed markedly enhanced survival after infection compared to adult mice. Both innate and adaptive immune components appear to contribute to this phenomenon. First, the increased resistance of neonates coincided with containment of the bacteria in the intestinal tissue with low dissemination into the spleen and liver. In contrast, the bacteria readily disseminated to the peripheral tissues in adult mice. Flow cytometric and histological studies revealed increased levels of neutrophils and macrophages in the neonatal mesenteric lymph nodes (MLN) compared to adult mice. Similar results were obtained using two different high virulence Y. enterocolitica strains. The rapid mobilization of innate cells sequestered the bacteria to the intestinal tissue, since in vivo neutrophil depletion led to efficient dissemination of Y. enterocolitica to the spleen and liver of neonates. Together, these results support the hypothesis that the neonatal intestinal immune system is competent to mount a strong antibacterial response by rapidly mobilizing innate phagocytes and thereby confining the bacterial infection to the gut, resulting in a high level of resistance. Second, we have also demonstrated that the adaptive immune system was mobilized during primary and secondary infection with this pathogen and that some of these factors may contribute to the enhanced resistance of neonatal mice to infection. Primary infection in neonates led to increased levels of antigen presenting cells, B and T cells with an activated phenotype in the MLN. MLN CD4+ Th cells from infected neonates were found to produce greater levels of IFN-gamma and IL-17A, compared to CD4+ Th cells from adult mice. These Th responses are likely to be functionally significant because neonatal mice deficient in CD4+ T cells were found to be more susceptible than adult mice to primary infection. CD4+ T cells adoptively transferred into CD4 deficient mice rescued the majority of mice from lethal infection and led to the production of IFN-gamma and IL-17A by MLN cells. In addition, primary T cell-dependent IgG1 and IgG2a serum antibodies specific for the Yersinia immunogen LcrV were increased compared to adult mice, and the absence of B cells partially increased the susceptibility of neonatal mice to primary infection. During secondary infection, however, neonatal and adult mice mounted quantitatively and qualitatively similar Yersinia-specific memory antibody responses, demonstrating that infection with Y. enterocolitica promotes mature B cell responses in neonatal mice. Finally, primed neonatal and adult mice were protected from colonization of the Peyer's patches, weight loss and mortality after a lethal infection in adulthood, demonstrating the development of long-lived protective memory responses at the intestinal interface. Together, these results indicate that both B and T cell responses, in particular Th1 and Th17 associated immunity, are important for the development of long lasting immunity to this pathogen in early life. Third, infection of neonatal mice with a Y. enterocolitica strain deleted of the anti-inflammatory protein YopP led to massive infiltration and/or accumulation of innate phagocytes in the intestine and MLN. This effect was not detectable in infected adult mice. Thus, we have identified a novel negative regulator of intestinal inflammation which might be valuable in preventing or ameliorating inflammatory conditions. This model system has revealed the unprecedented potential of neonatal mice to develop protective inflammatory innate and adaptive immunity at mucosal surfaces. The combined results presented here demonstrate that neonatal mice may be well equipped to mount robust innate and adaptive intestinal inflammatory responses that are highly protective toward Y. enterocolitica. These findings have implications for understanding how pediatric intestinal adaptive immune responses develop in response to naturally occurring gastroenteric pathogens and offer a new biological platform for development of vaccines aimed at improving mucosal and systemic immunity in early life.

Styles APA, Harvard, Vancouver, ISO, etc.

16

Roberts, Morgan. « The role of the Lyn tyrosine kinase in innate immunity and intestinal inflammation ». Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/54079.

Texte intégral

Résumé :

The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
Science, Faculty of
Microbiology and Immunology, Department of
Graduate

Styles APA, Harvard, Vancouver, ISO, etc.

17

Wang, Gaochan. « Diarrheagenic Escherichia coli signaling and interactions with host innate immunity and intestinal microbiota ». Diss., Kansas State University, 2017. http://hdl.handle.net/2097/35735.

Texte intégral

Résumé :

Doctor of Philosophy
Department of Diagnostic Medicine/Pathobiology
Philip R. Hardwidge
Diarrheagenic Escherichia coli (E. coli) strains are common etiological agents of diarrhea. Diarrheagenic E. coli are classified into enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC or enterohemorrhagic E. coli [EHEC]), enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), diffuse-adherent E. coli (DAEC), and adherent invasive E. coli (AIEC). In addition to encoding toxins that cause diarrhea, diarrheagenic E. coli have evolved numerous strategies to interfere with host defenses. In the first project, we identified an ETEC-secreted factor (ESF) that blocked TNF-induced NF-[kappa]B activation. One of the consequences of TNF-induced NF-[kappa]B activation is the production of pro-inflammatory cytokines that help to eliminate pathogens. Modulation of NF-[kappa]B signaling may promote ETEC colonization of the host small intestine. In this study, we fractionated ETEC supernatants and identified flagellin as necessary and sufficient for blocking the degradation of the NF-[kappa]B inhibitor I[kappa]B[alpha] in response to TNF[alpha]. In the second project, we attempted to identify an ETEC cAMP importer. ETEC diarrhea leads to cAMP release into the lumen of the small intestine. cAMP is a key secondary messenger that regulates ETEC adhesin expression. We hypothesized that a cAMP importer is present in ETEC, accounting for its hypersensitivity to extracellular cAMP. We used Tn5 transposome-mediated mutagenesis to construct a mutant library and screen for cAMP-hyporesponsive mutants. However, none of the 17,956 mutants we screened were cAMP-hyporesponsive. In the third project, we focused on gut microbiota and the T3SS effector NleH. We used the mouse-specific pathogen C. rodentium and transplanted performed microbiota between different mouse strains. We evaluated microbiota populations as a function of infection with WT and [Delta]nleH C. rodentium strains before and after microbiota transplantation. Microbiota transfer altered the resistance to WT C. rodentium infection in C57BL/10ScNJ mice and the NleH effector promoted host resistance to C. rodentium.

Styles APA, Harvard, Vancouver, ISO, etc.

18

Wang, Xin. « INTESTINAL IMMUNITY AND GUT MICROBIOTA IN ALDO-KETO REDUCTASE 1 B8 DEFICIENT MICE ». OpenSIUC, 2019. https://opensiuc.lib.siu.edu/dissertations/1723.

Texte intégral

Résumé :

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death in the United States. Aldo-keto reductase 1 B10 (AKR1B10) is highly expressed in colon and small intestine of normal humans, but its expression is lost or markedly down-regulated in tissues of patients with ulcerative colitis (UC) and CRC. AKR1B10 is a monomeric cytosolic enzyme with strong enzymatic activity to α, β-unsaturated carbonyl compounds, protecting cells from carbonyl lesions; AKR1B10 also mediates de novo synthesis of long chain fatty acids and membrane lipids, such as phosphatidylinositol 4,5-bisphosphate (PIP2). To study the etiopathogenic role of AKR1B10 in UC and CRC, our lab generated AKR1B8 deficient (AKR1B8 -/-) mice. AKR1 B8 is the orthologue in mice of human AKR1B10,

Styles APA, Harvard, Vancouver, ISO, etc.

19

Ambrose, Timothy James William. « Serine hydrolase activity and roles for monoacylglycerol lipase in innate immunity and intestinal inflammation ». Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:f7a12796-ae8f-4121-ab1a-26778261ac78.

Texte intégral

Résumé :

Detection of evolutionarily conserved pathogen motifs by pattern recognition receptors (PRRs), particularly on dendritic cells (DCs), is crucial for adequate immune responses. Defects in DC function are known to be associated with inflammatory bowel disease (IBD). The endocannabinoid system (ECS) is the system through which exocannabinoids such as Δ⁹-tetrahydrocannabinol and cannabidiol signal. Regarding inflammation, cannabinoids generally exert anti-inflammatory effects, including on experimental colitis. However, most work has been performed in animal models and less is known about the function of this system in human immune cells, particularly DCs. Monoacylglycerol lipase (MGLL) is the key enzyme for hydrolysis of the endocannabinoid 2-arachidonoylglycerol, and a member of the serine hydrolase enzyme superfamily. This thesis defines the activity of serine hydrolase enzymes for the first time in human DCs upon stimulation by NOD2/TLR2 ligands using activity-based protein profiling (ABPP). MGLL is shown to be ubiquitously upregulated upon stimulation of DCs and in monocyte-derived macrophages. Through pharmacological inhibition studies, MGLL is demonstrated to regulate cellular and secreted lipids, not limited to endocannabinoids. However, overall DC function is independent of this enzyme suggesting that the effects of lipid modulation may be on bystander cells. Challenging the current literature, MGLL inhibition with a novel inhibitor worsens murine Citrobacter rodentium colitis. Finally, ABPP demonstrates a rich serine hydrolome in colonic tissue from human IBD with many enzymes previously undefined in this disease. Gene expression of ECS components suggests the enzymes ABHD12 and DAGLα/β may be potential markers of field change in IBD.

Styles APA, Harvard, Vancouver, ISO, etc.

20

Ou, Gangwei. « Human intestinal epithelial cells in innate immunity : interactions with normal microbiota and pathogenic bacteria ». Doctoral thesis, Umeå : Umeå University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-18388.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

21

Cima, Igor. « Glucocorticoid synthesis in the intestinal mucosa and its role in local T cell immunity / ». [S.l.] : [s.n.], 2005. http://www.zb.unibe.ch/download/eldiss/04cima_i.pdf.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

22

Platt, Andrew M. « Intestinal macrophages in health and inflammation ». Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/690/.

Texte intégral

Résumé :

The healthy large intestinal mucosa contains a vast pool of macrophages (mφ) that are close to the local bacterial flora and have several unique phenotypic and functional properties compared with other mφ populations. Although human colonic mφ retain some of the hallmark functions of mφ, such as the ability to phagocytose particulate material and exert bactericidal activity, they are unable to produce pro-inflammatory mediators. Thus it has been suggested that intestinal mφ are functionally adapted to the microbe-rich, immunostimulatory environment of the gut, where strong inflammatory responses to harmless commensal bacteria would lead to continuous inflammation and ultimately tissue pathology. Indeed, there is mounting evidence that mφ play an essential role in maintaining homeostasis and epithelial renewal in the normal intestine. In contrast, mφ from the intestine of patients with inflammatory bowel disease (IBD) differ markedly from those present physiologically, exhibiting heightened inflammatory and bactericidal activities, and contributing to the tissue damage. How these differing properties of colonic mφ are controlled and how this potentially dangerous population is kept quiescent under physiological conditions are important questions. Most existing information comes from either simple, observational studies of human tissue, or from work on cell culture systems which aim to reproduce the unusual phenotype of resident intestinal mφ in vitro. Importantly analogous experiments of resident and inflammatory mφ have not been carried out in murine systems, where it would be possible to characterise the cells fully and explore their origin, function and role in inflammatory processes. Therefore, the aims of this thesis were first to characterise mφ in the resting murine colon both functionally and phenotypically, focussing particularly on their expression of toll-like receptors (TLR) and responsiveness to TLR ligation and on their population dynamics in vivo. By comparing colonic mφ with other tissue mφ populations, I hoped to gain an understanding of how resident gut mφ might have adapted to their local environment. In the second part of my work, I examined how the properties of colonic mφ altered in inflammation, employing a well-established experimental model of colitis, with the aim of determining how resident and inflammatory mφ might relate to each other. Lastly, I explored the effects of the ES-62 parasite product, known to have potent anti-inflammatory effects on mφ, on experimental colitis in vivo. Experiments detailing my initial characterisation of the myeloid cells expressing the F4/80 mφ marker in the colon of normal mice are described in Chapter 3. These revealed that the F4/80+ population in the gut is extremely heterogeneous compared with other mφ populations in the body. Virtually all in vitro-differentiated BM mφ (BMM) and mφ from the resting peritoneum (PEC mφ) exhibited the conventional F4/80+CD11b+CD11c- phenotype of classical mφ and upregulated costimulatory molecules in response to TLR ligation. In stark contrast, the colon contained three F4/80+ subsets, one F4/80+CD11b+CD11cint, one F4/80+CD11b+CD11c- and a smaller population of F4/80+CD11b-CD11c- cells. None of these subsets expressed co-stimulatory molecules, even after LPS stimulation, but unlike other mφ, the majority of colonic mφ expressed high levels of class II MHC without stimulation. BMM and PEC mφ also produced several pro-inflammatory cytokines and chemokines following stimulation, whereas colonic mφ showed no mediator production under these conditions. Nevertheless, colonic mφ did retain avid endocytic and phagocytic activities, indicating that colonic mφ may engulf bacteria without initiating inflammation. In Chapter 4, I explored the unresponsiveness of resting colonic mφ to microbial stimuli in more detail and found that the TLR refractoriness is associated with reduced expression of TLR2, 3, 4 and 9. Apart from a small proportion of mφ that retained TLR2 expression, TLR expression was downregulated both at the protein level and to some extent also at the mRNA level; TLRs were not re-expressed following ex vivo culture of purified mφ. This global downregulation of TLRs could not be reproduced in BMM by treatment with TLR ligands, and was also present in colonic mφ taken from mice unable to signal via TLR2 or TLR4, suggesting it was not simply a form of endotoxin “tolerance”. However, the mechanism seemed to involve IL-10, as colonic mφ from IL-10-deficient animals displayed a heightened level of TLR expression and responsiveness, even prior to the onset of intestinal inflammation. In Chapter 5, I examined the phenotype and function of mφ during the experimental colitis induced by feeding dextran sodium sulphate (DSS). During inflammation, the absolute number of F4/80+ mφ increased 6-fold, the majority of which now expressed TLR, CD11b and low levels of CD11c. This new population of colitic mφ also expressed class II MHC, low levels of co-stimulatory molecules and produced large amounts of TNFα. In Chapter 6, I went on to examine the population dynamics of colonic mφ under resting conditions and during inflammation, showing that the overall turnover rate of the total mφ population was increased during colitis, as assessed by uptake of BrdU in vivo. The increased turnover was mainly due to the TLR-expressing, TNFα+ population of mφ and more detailed analysis showed that the small number of these cells present in resting colon had identical turnover rates to those found in colitis. In contrast, the TLR negative mφ had much lower turnover rates in resting and inflamed colon, suggesting that the TLR+ and TLR- subsets may represent distinct mφ populations with different population dynamics, and that during intestinal inflammation, the TLR+ subset may display a preferential recruitment into the gut. Indeed, proliferation in situ was minimal, indicating that the recently divided, TLR-expressing mφ proliferated outside the intestine before being recruited into the gut. My subsequent experiments suggested that this recruitment may involve the CCR2 chemokine receptor, which was expressed at high levels specifically by the TLR+ subset of mφ both in resting and inflamed colon. Finally in Chapter 7, I treated colitic mice with ES-62, a phosphorylcholine (PC)-containing glycoprotein secreted by the filarial nematode, Acanthocheilonema viteae, which has been shown to modulate pro-inflammatory cytokine production by mφ in vitro. ES-62 treatment had no significant effect on weight loss or pro-inflammatory cytokine production in the colon of mice with DSS colitis, although it slightly delayed the onset of the clinical signs of disease. Thus further studies of ES-62 as a modulator of mφ-dependent intestinal inflammation may be warranted. Taken together, my data suggest that under resting conditions, intestinal mφ are heterogeneous and adapt to their microenvironment by being non-inflammatory via active downregulation of TLR expression and function, which may be partly dependent on IL-10. During inflammation, large numbers of TLR expressing, fully responsive mφ appear, probably via CCR2-dependent recruitment of recently divided blood-derived monocytes. Interestingly, small numbers of these TLR-expressing, rapidly turning over mφ are also present in normal colon and my data suggest that these pro-inflammatory mφ may be quite distinct from the more sessile mφ which are the dominant “resident” population in normal gut. A delicate balance between these two mφ populations must ensure homeostasis and appropriate responses to inflammation.

Styles APA, Harvard, Vancouver, ISO, etc.

23

Barbosa, José Guilherme Morschel. « Efeitos da suplementação de levedura autolisada de Saccharomyces cerevisiae sobre o desempenho e a imunidade intestinal de frangos de corte ». Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/11/11139/tde-18052017-152408/.

Texte intégral

Résumé :

O objetivo do estudo foi avaliar os efeitos da suplementação de levedura autolisada de Saccharomyces cerevisiae fornecida em duas diferentes inclusões em dietas para frangos de corte como alternativa a um antimicrobiano sobre desempenho zootécnico e avaliação do sistema imune intestinal pela realização da enumeração bacteriana, citometria de fluxo e expressão intestinal de genes ligados à resposta imune intestinal. Neste estudo foram utilizados 1260 pintos de corte machos de um dia de idade da linhagem ROSS AP95® em um experimento de 1 a 35 dias de idade alojados em galpão climatizado com cama de casa de arroz nova. O experimento foi realizado em delineamento inteiramente aleatorizado, com 4 tratamentos e 7 repetições, com 45 aves por boxe. Os tratamentos utilizados foram: T1: ração basal e sem aditivo - controle negativo; T2: ração basal suplementada com 55 ppm de bacitracina de zinco - controle positivo; T3: controle negativo + 2 kg/t de levedura autolisada; T4: controle negativo + 4 kg/t de levedura autolisada. As dietas foram à base de milho e farelo de soja, sendo adicionados às rações 5% de farelo de trigo e 5% de farinha de penas e vísceras (sem tratamento prévio) com objetivo de impor um desafio nutricional aos animais. Ainda visando estimular imunologicamente os animais, aos 7 dias de idade, todas as aves foram desafiadas via ocular com uma vacina viva contendo oocistos de Eimeria sp. na dose recomendada pelo fabricante. Aos 8 dias de idade e 21 dias de idade, uma ave de cada unidade experimental, sem jejum prévio, teve sangue coletado e foi sacrificada para coleta de conteúdo intestinal ileal e cecal para realização da emumeração bacteriana de Enterococus sp., Escherichia coli e Lactobacillus sp., e para a coleta do segmento ileal para avaliar a expressão gênica intestinal de Claudin-1, IL-1β, IL-4, TLR4 e MUC-2 através da PCR em tempo real. Em relação ao desempenho das aves, o tratamento T3 propiciou melhor conversão alimentar em relação a T1 até os 21 dias de idade. Para o período cumulativo, o tratamento T4 propiciou conversão alimentar semelhante ao T2, sendo esta variável melhor para estes tratamentos em relação ao controle negativo. Na enumeração de bactérias no íleo, aos 8 dias de idade, os tratamentos T3 e T4 modularam de forma distinta a contagem de Enterococus sp., e para o gênero Lactobacillus sp., ambos os grupos de levedura apresentaram menor contagem em contraste com o controle positivo. No conteúdo do ceco foi encontrado um menor número de E. coli para os animais grupo T3, diferentemente para o T2 que propiciou maior contagem. Aos 21 dias de idade, foi encontrado diferença na enumeração do gênero Enterococus sp. ileal, cuja contagem foi menor para o T2 em relação ao T1. Na na análise de citometria de fluxo, tendências foram observadas aos 8 dias de idade para o percentual de linfócitos T auxiliares (P=0,16) e para o percentual de linfócitos B (P=0,12) havendo redução com a suplementação de levedura autolisada. A mesma tendência (P=0,19) foi observada aos 21 dias de idade para a contagem de células T citóxicos. Sobre a PCR em tempo real, não foram detectadas diferenças para a expressão de Claudin-1. T2 e T4 propiciaram aumento da expressão gênica de IL-1β aos 21 dias de idade em relação ao controle negativo, sendo que T2 também promoveu aumento de TLR-4 aos 8 dias de idade. Tendências foram observadas com a maior expressão de IL-4 (P=0,06) aos 21 dias de idade pelo T2 e aumento na expressão de MUC-2 (P=0,09) pelo T4 aos 8 dias de idade. Os diferentes padrões de ativação ou não de citocinas revela uma estimulação da via Th2 pelo controle positivo (aumento de IL-1β e IL-4) e da via Th17 pelo tratamento suplementado com 4 kg/t de levedura autolisada (aumento de IL-1β).
The objective of this study was to evaluate the effects of a Saccharomyces cerevisiae autolyzed yeast supplementation in substitution of AGP in broiler diets on performance and immune system (on two different feed inclusions for broilers diets in replacing AGP on broiler performance and evaluation of immune system trough bacterial enumeration, flux citometry and intestinal gene expression. For that, 1260 one-day-old male Ross AP95 chicks were raised from 1 to 35 days of age in a poultry house with new rice husk as litter. The experiment was arranged in a completely randomized design with 4 treatments and 7 replications, with 45 birds per pen. The treatments were: T1: basal diet and no additive - negative control; T2: basal diet supplemented with 55 ppm of zinc bacitracin - positive control; T3: negative control + 2 kg/t of autolyzed yeast; T4: negative control + 4 kg/t of autolyzed yeast. The corn-soybean meal based diets contained 5% wheat bran and 5% poultry by-product meal (with no previous treatment) in order to impose a nutritional challenge to the animals. To impose a further immunological challenge, at 7 days of age, all the birds were eye drop-vaccinated with live vaccine containing Eimeira sp. oocysts at the manufacturer recommended dosis. At 8 and 21 days of age, one chick per experimental unit, with no fasting, had the blood collected and was sacrificed for sampling the ileal and cecal intestinal contents for enumeration of Enterococus sp., Escherichia coli and Lactobacillus sp. Also, the ileal segment was sampled for intestinal gene expression of Claudin-1, IL-1β, IL-4, TLR4 e MUC-2 by RNA extraction through real time PCR. For the performance results at 21 days of age, T3 had the same feed conversion rate of T1. For the cumulative grow-out, T4 had the same feed conversion rate as T2, being this variable better for the aforementioned tretaments in comparison to negative control. For ileal bacterial enumeration, at 8 days of age, T3 and T4 modulated distinctly the enumeration of Enterococus sp., and reduced the counts of Lactobacillus sp. in comparison to the positive control. In the cecal contents, the enumeration for E. coli was the lowest for T3, differing from the positive control. At 21 days of age, there was a difference in ileal Enterococus sp., with higher counts for T2 relative to T1. In the flux citometry, tendencies were observed at 8 days of age for T helper cells (P=0,16) and for B cells (P=0,12), which were reduced in the autolyzed yeast treatments. The same tendency (p=0.19) was seen at 21 days of age for T activated cytotoxic cells. For the real time PCR, there was no difference in the expression of Claudin-1 (P<0,05). T2 and T4 promoted upregulation of IL-1β at 21 days of age (P<0,05) in comparison to the negative control; additionally, the antibiotic tretatment also upregulated the expression of TLR-4 at 8 days of age (P<0,05). Tendencies were observed as upregulation of IL-4 (P=0,06) at 21 days of age by positive control and upregulation of MUC-2 (P=0,09) by the treatment with 4 kg/t of autolyzed yeast at 8 days of age. The different profiles in activating or not cytokines reveals a stimulation of Th2 pathway for the positive control (upregulation of IL-1β and IL-4) and Th17 pathway for the treatment supplemented with 4 kg/t of autolyzed yeast (upregulation of IL-1β).

Styles APA, Harvard, Vancouver, ISO, etc.

24

Zeng, Yi. « Optimizing immunity against BCR-ABL positive leukemia ». Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/289963.

Texte intégral

Résumé :

Chronic myelogenous leukemia (CML) is a clonal disorder characterized by proliferation of cells expressing BCR-ABL fusion proteins. The BCR-ABL fusion proteins are tumor-specific antigens and represent reasonable targets for immunologic approaches against CML. We have utilized a free-solution-isoelectric focusing technique (FS-IEF) to obtain chaperone rich cell lysates (CRCL) from tumors. We found that CRCL derived from 12B1, an aggressive bcr-abl⁺ murine tumor activated dendritic cells (DCs) by upregulating CD40 and MHC-II on their cell surface and stimulating them to produce interleukin-12 (IL-12). Vaccination of mice with 12B1 CRCL pulsed DCs generated potent, tumor specific, long lasting, CD4⁺ and CD8⁺ T cell dependent immune responses. We have further demonstrated that immunization with 12B1 CRCL induced BCR-ABL specific cytotoxic T lymphocytes, indicating that BCR-ABL peptides are chaperoned by CRCL and are cross-presented to CD8⁺ T cells. Moreover, other antigenic peptides may also be present in the antigen repertoire of CRCL and contribute to the superior immunogenicity of 12B1-derived CRCL. To better optimize immunity against CML, we investigated the effects of combining imatinib mesylate with 12B1 CRCL. Imatinib mesylate specifically inhibits BCR-ABL kinase activity and has been very successful in treating patients with CML. However, the development of drug resistance has led to drug combination approaches. We have shown that the combination of imatinib with DCs loaded with 12B1-derived CRCL yielded potent anti-tumor activity. In addition to tumor-derived heat shock proteins, we have also studied the immunogenicity of apoptotic leukemic cells. We have previously reported that vaccination of mice with stressed apoptotic leukemic cells elicited potent anti-tumor immunity. We have found that stressed apoptotic leukemic cells, compared with non-stressed apoptotic ones, have higher capacity to upregulate CD40, CD80, and CD86 on the surface of DCs, to stimulate DCs to secrete IL-12, and to enhance their immunostimulatory functions in a mixed lymphocyte reaction (MLR). These findings demonstrate that apoptotic tumor cells can be immunogenic when stressed, and that DCs play a key role in determining whether a T cell response will be generated.

Styles APA, Harvard, Vancouver, ISO, etc.

25

Nohr, Carl William. « Humoral immunity in surgical patients ». Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75969.

Texte intégral

Résumé :

Humoral immune function was studied in surgical patients. The antibody response to vaccination with a protein antigen, tetanus toxoid (TT), was reduced among all patients, especially those with reduced delayed type hypersensitivity (DTH) and increased degree of physiological derangement. The antibody response to a polysaccharide antigen, pneumococcal polysaccharide (PPS), was normal. In trauma patients, the antibody response to TT was normal. The in vitro production of specific and total immunoglobulin (Ig) by blood mononuclear cells was studied. Patients that failed to produce a serum antibody response to TT also failed to produce anti-TT in vitro. Anti-PPS production was normal. More total Ig was produced by patients, especially those with reduced DTH responses. Some patients showed a reduction, rather than the normal increase, in Ig synthesis with mitogen stimulation. These data show evidence of humoral immune deficiency to protein antigens, and in vivo activation of the B cell system.

Styles APA, Harvard, Vancouver, ISO, etc.

26

Haghayeghi, Amirhossein. « Pellino function in «Drosophila» innate immunity ». Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86930.

Texte intégral

Résumé :

The Toll pathway mediates innate immunity, the first line of defense against pathogens in vertebrates and invertebrates. In Drosophila the Toll pathway protects against Gram-positive bacteria and fungi by inducing antimicrobial peptides such as Drosomycin. Pellino is a highly conserved protein which biochemically interacts with Pelle/IRAK, a crucial kinase downstream of Toll. Here we report that the chemically induced Pellino 7T2 mutant does not affect Toll pathway function in early embryonic dorsoventral patterning, but it severely compromises induction of Drosomycin upon infection with Gram-positive Micrococcus luteus. In this study we identify Pellino as a novel component of Toll pathway-mediated innate immunity.
La transduction de signal initiée par Toll active l'immunité innée. Cet événement constitue la première ligne de défense contre des agents pathogènes chez les vertébrés et les invertébrés. Dans la Drosophile, la transduction de signal initiée par Toll protège contre les bactéries Gram-positives et les champignons en induisant la production de peptides antimicrobiens tels que Drosomycin. Pellino est une protéine hautement conservée qui interagit biochimiquement avec Pelle/IRAK, une kinase essentielle activée par Toll. Ici, nous reportons que Pellino 7T2, un mutant chimiquement induit, n'affecte pas la fonction de Toll durant l'établissement de la polarité dorsoventral dans les embryons précoces. Cependant, Pellino affecte l'induction de Drosomycin suite à une infection avec les bacteries Gram-positive Micrococcus luteus. Dans cette étude, nous reportons un nouveau rôle à Pellino, notamment, celui d'un élément de la voie de signal initiée par Toll qui impacte l'immunité innée.

Styles APA, Harvard, Vancouver, ISO, etc.

27

Nyangahu, Donald D. « Alterations in preconception, antenatal, and postnatal maternal gut microbiota influence offspring intestinal microbiota and immunity ». Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/25479.

Texte intégral

Résumé :

Maternal microbiota during pregnancy, as well as maternal disease state, may impact offspring gut bacterial colonisation. Here, we explore the impact of maternal antibiotics during gestation and/or nursing on offspring gut microbiota. Further, we investigate the effect of preconception helminth infections on maternal and infant gut microbiota. For maternal antibiotic experiments, dams were fed vancomycin, polymyxin B, or both, in drinking water during gestation, nursing or gestation plus nursing, and their offspring microbiota analysed at 14 days of life, alongside immunity in the spleens. Offspring born to vancomycin treated mothers had significantly higher relative abundance of Proteobacteria and Tenericutes while maternal oral polymyxin B led to significantly lower abundance of Proteobacteria and Deferribacteres in infants. Maternal oral vancomycin led to significant reduction in proportions of infant central memory CD4+ T cells (CD4+CD44hiCD62Lhi) regardless of antibiotic timing. Effector memory CD4+ T cells were significantly lower in pups born to dams treated with polymyxin B while nursing while proportions of central memory CD4 T cells were significantly increased in gestation only or gestation plus nursing pups. In addition, oral vancomycin in dams during nursing resulted in significantly reduced proportions of both total and follicular B cells in offspring born to antibiotic treated dams. Pups born to Vancomycin treated mothers had a significant delay in growth when infected with Respiratory Syncytial Virus (RSV). On the other hand, pups born to mothers treated with Polymyxin B during gestation or gestation plus nursing were susceptible to Nippostrongylus brasiliensis (Nb) infection. In the second study, we infected female BALB/c mice with 500Nb L3 three weeks prior to mating and examined the effect of preconception helminth infection on offspring microbiota and immunity. Preconception Nb infections led to alterations of maternal gut microbiota during pregnancy. In addition, we observed dramatic differences in offspring microbiota in pups born to previously helminth infected dams. Coriobacteriaceae were predominant in pups born to previously Nb infected dams when compared to uninfected dams. Overall, manipulation of maternal microbiota during gestation or lactation profoundly impacts offspring growth, intestinal microbiota and immunity to RSV and helminths.

Styles APA, Harvard, Vancouver, ISO, etc.

28

Morris, Bruce C. « Intestinal Mucosal Mast Cell Immune Response and Pathogenesis of Two Eimeria Acervulina Isolates in Broiler Chickens ». Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/36228.

Texte intégral

Résumé :

Five experiments were conducted comparing differential intestinal immune responses to two isolates of Eimeria acervulina (EA), EA1 and EA2. In three experiments, broiler chicks were divided into control (non-challenged), EA1, or EA2 challenged (14 days of age) groups. On day 6 post-challenge (PC), changes in body weight were determined, intestinal lesions were scored, and duodenal tissue was evaluated for morphometric alterations and mucosal mast cell responses. EA1 produced duodenal lesions and reduced villus height to crypt depth ratios when compared to controls; however, no differences were found in mast cell counts. EA2 produced differing results, and observed data were suggestive of an intestinal secretory response when compared to EA1 or controls. In Experiment 4, tissues were analyzed from day 2 through day 6 PC. Villus atrophy and crypt hyperplasia were heightened on day 5 PC in both challenged groups. Mast cell counts were significantly greater on days 3 and 4 PC in EA1 birds. In Experiment 5, EA2 oocysts were cleaned with 5.25% sodium hypochlorite to evaluate the possibility of a bacterial contaminant contributing to the pathogenesis of intestinal alterations. Weight gains were decreased by challenge and villus heights and crypt depths were significantly altered in challenged birds, resulting in lower villus to crypt ratios, however, there were no differences in mast cell number. These data are indicative of differential host response and immunovariability between different isolates of the same Eimeria species and are suggestive of mast cell involvement in coccidial immunity in broiler chickens.
Master of Science

Styles APA, Harvard, Vancouver, ISO, etc.

29

Chowdhury, Abeed. « Infection and immunity in health and surgical disease ». Thesis, University of Nottingham, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665483.

Texte intégral

Résumé :

Advances in surgical technology, critical care and antimicrobial therapy have improved outcomes for patients undergoing major abdominal surgery. However, for some patients, the risk of complications remains considerably high. It is recognised that sepsis due to bacterial infection is a major aetiological factor leading to postoperative major organ dysfunction. Current therapies to combat rates of infection rely far too heavily on antibiotics, to which there is growing resistance, leading to the demand for novel or alternative strategies The aim of this series of studies was to demonstrate the influence of bacteria and their products on human immune responses in both health and surgical disease. Previous studies indicate a potential role for probiotic bacteria in the treatment of infective disorders of the gastrointestinal tract. In this thesis, it is demonstrated using meta-analytical methods, that probiotic and synbiotic bacteria reduce the risk of infective complications following major abdominal surgery. It is proposed that some of the beneficial effects of probiotics involve modulation of host immune responses. In this thesis, it is demonstrated that probiotic treatment in healthy volunteers confers changes in the expression of Foxp3, the transcription factor characteristic of T regulatory cells. In addition, expression of cell surface proteins on dendritic cells (DCs) following synbiotic treatment has indicated expansion of mature DC subsets with altered phenotype.

Styles APA, Harvard, Vancouver, ISO, etc.

30

Coakley, Gillian. « Characterisation of secreted exosomes from the intestinal nematode Heligmosomoides polygyrus ». Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/23464.

Texte intégral

Résumé :

The parasite secretome has been shown to play a key role in both pathogenicity and the regulation of host defence, allowing pathogens, such as helminths, to establish a chronic infection within the host. The recently discovered presence of extracellular vesicles within parasite-derived excretory-secretory products introduces a new mechanism of potential cross-species communication. Extracellular vesicles (EVs), such as exosomes, facilitate cellular communication through the transfer of small RNAs, lipids and proteins between cells and organisms across all three kingdoms of life. In addition to their roles in normal physiology, EVs also transport molecules from pathogens to hosts, presenting parasite antigens and transferring infectious agents. Here, I examine secreted vesicles from the murine gastrointestinal nematode Heligmosomoides polygyrus, and their potential role in the host-helminth interactions. Transmission electron microscopy reveals vesicle-like structures of 50- 100 nM in the ultracentrifuged secretory product, and potential evidence of multi-vesicular bodies in the worm intestine. This, coupled with information from the exoproteome, helped support the hypothesis that exosomes originate from the parasite intestinal tract. I have completed a series of studies looking at the fundamental properties of exosome-cell interactions, providing comparative studies between mammalian and H. polygyrus-derived exosomes. I have determined some of the key factors influencing exosome uptake, including time of incubation, cell type and exosome origin. Through microarray analysis of H. polygyrus exosome-treated small intestinal epithelial cells, we see significant gene expression changes, including those involved in the regulation of signalling and the immune response, such as DUSP1 (dual-specificity phosphatase) and IL1RL1 (the receptor for IL-33). The modest reduction of inflammatory cytokine responses by exosomes in small intestinal cell lines was amplified in immune cells, such as macrophages. Exosomes can significantly reduce expression of classical activation markers, as well as inflammatory cytokine production in the macrophage cell line RAW 264.7, and this is further supported by similar responses in bone marrow-derived macrophages. Owing to their suppressive nature, I demonstrate that immunization of mice with an exosome/alum conjugate generates significant protection from a subsequent H. polygyrus larval challenge, as seen through a reduction in egg counts and worm burden. I have investigated the role of the IL33 receptor (IL-33R); a key molecule associated with parasitic resistance that is suppressed by exosomes in type-2 associated immune responses. Uptake of H. polygyrus-derived exosomes by alternatively activated macrophages caused the suppression of type 2 cytokine/protein release and the reduction of key genes associated with this phenotype. In addition, there was also significant repression of both transcript and surface T1/ST2, a subunit of the IL-33R). Using a model of lung inflammation, in vivo studies demonstrate that, in both prophylactic and co-administration experiments, exosomes modulate the innate cellular response. This is represented by changes in the number of innate lymphoid cells (ILCs), bronchoalveolar lavage eosinophils and type-2 cytokine output. In this system, the expression of T1/ST2 on type 2 ILCs was also significantly reduced. I have extended the investigation on exosome-IL-33R responses by using T1/ST2 knockout mice. Despite generating strong antibody responses, vaccination against exosomes could not protect T1/ST2 knockout mice against a subsequent infection. This work suggests that exosomes secreted by nematodes could mediate the transfer and uptake of parasite products into host cells, establishing cross-species communication to suppress the host ‘danger’ or inflammatory response.

Styles APA, Harvard, Vancouver, ISO, etc.

31

Makedonas, George. « Cellular immunity among HIV exposed, uninfected individuals ». Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111828.

Texte intégral

Résumé :

Two models of HIV infection have been studied extensively with the goal of identifying immune correlate(s) of protection against HIV: (1) the simian immunodeficiency virus (SIV) infection of rhesus macaque monkeys and (2) individuals with repeated exposure to HIV who remain uninfected by the virus (EUs). Both paradigms suggest that T cell-mediated immunity plays an important role in controlling HIV replication. Evidence from the SIV/macaque system, however, predicts that HIV vaccines aimed at eliciting T cell responses will fail to induce sterilizing immunity against HIV. The aim of the work presented in this thesis was to correlate HIV-specific T cell immunity in EUs with protection from HIV infection. The study cohort was comprised of (a) men who have unprotected sexual intercourse with HIV-infected men (MSM), (b) intravenous drug users (IVDU) who share syringes with HIV-infected peers, and (c) heterosexual partners of HIV-infected subjects. EUs were shown to exhibit HIV-specific IFN-gamma secretion, IL-2 production, and T cell proliferation, whereas low-risk negative controls did not. Furthermore, HIV-specific IFN-gamma secretion and T cell proliferation were not observed among a population of EUs who seroconverted soon after the tested time point. HIV-specific IL-2 secretion and T cell proliferation were shown to be correlated in our cohort of EUs. These effector functions are considered hallmark properties of central memory T cells (TCM), the subset of memory T cells that has been shown to mediate sterilizing immunity in mouse models of viral infection. The presence of TCM in EUs implies the development of immunity against HIV that is either fully protective or partially so, by increasing the threshold for HIV infection. Since these HIV-specific effector functions were absent in EUs who eventually seroconverted, it can be inferred that EUs in our cohort develop HIV-specific T cell immunity that mediates protection from HIV infection. Thus, our contribution to the EU paradigm is that sterilizing immunity is an attainable goal of prospective HIV vaccines.

Styles APA, Harvard, Vancouver, ISO, etc.

32

Lei, Andrea. « Inflammasome regulation and activation in the intestinal epithelium ». Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:6db34fe2-36ae-44f4-a4ac-2464a333c8f8.

Texte intégral

Résumé :

Microbiota colonisation of the intestinal tract makes it difficult for pattern recognition receptors (PRR) to discriminate between beneficial microbes and harmful pathogens. We aim to define the roles of cytosolic Nod-like receptors (NLR) in intestinal immunity and homeostasis. Upon activation, some NLR form inflammasomes that mediate the release of inflammatory cytokines and pyroptosis, an inflammatory form of cell death. NLR activation in the non-hematopoietic compartment was shown to be protective during acute intestinal infection. To identify the cell type responsible for this protection, we generated transgenic mice in which the key inflammasome adaptor molecule Asc is selectively ablated in intestinal epithelial cells (IEC) (Asc^ΔVC) and observed that inflammasomes are important for controlling Citrobacter rodentium clearance in these mice. To further dissect the importance of pathogen clearance by IEC inflammasome, ex vivo cultures of primary IEC organoids were established. Thus far this system has revealed profound differences in inflammasome regulation between IEC organoids and bone marrow-derived macrophages (BMDM). This research will inform our understanding of cell type-specific regulation of inflammasomes.

Styles APA, Harvard, Vancouver, ISO, etc.

33

Wu, Muzo. « Innate Immunity Immunomodulators in Post-Influenza Bacterial Pneumonia ». Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:16121158.

Texte intégral

Résumé :

Post-influenza bacterial pneumonia is a major cause of morbidity and mortality worldwide. One mechanism for enhanced susceptibility to bacterial infection after influenza is down-regulation of a major phagocytic receptor on alveolar macrophages, macrophage receptor with collagenous structure (MARCO), by interferon- (IFN-), which leads to diminished bacterial clearance. Nrf2, a transcription factor that regulates expression of antioxidant genes, is one of the regulators of MARCO expression. We show that the Nrf2 activator sulforaphane improves MARCO expression and bacterial phagocytosis in alveolar macrophage (AM)-like human monocyte-derived macrophages (HMDMs). It also improves host survival by up-regulating MARCO in a murine model of post-influenza pneumococcal pneumonia. MARCO is spontaneously restored and upregulated in the later phase of influenza virus infection. Initially, elevated IFN levels following influenza infection coincide with attenuated MARCO expression in the lungs. However, as IFN levels returned to normal levels on post-influenza day 11, there was a striking 4.86-fold increase of MARCO expression compared to the low level observed on day 9. To identify regulatory mechanisms underlying this rebound or enhanced post-influenza MARCO expression, we performed RNA sequencing analysis of purified lung macrophages from post-influenza day 9 and 11. Among the differentially expressed genes between post-influenza day 9 and day 11 macrophages were MARCO and Akt. The Akt activator SC79 significantly increased MARCO expression on IFN-treated AM-like HMDMs, whereas the Akt inhibitor perifosine reduced MARCO expression on HMDMs. SC79 treatment significantly improved mouse survival in post-influenza pneumococcal pneumonia. Transcription factor E-box (TFEB) is one of the overrepresented transcription factors binding to candidate genes in our RNA sequencing analysis. SC79-induced MARCO expression in IFN-treated HMDMs was abrogated in TFEB knockdown cells compared to controls. The results suggest that Akt regulates MARCO expression through effects on the transcription factor TFEB. In summary, immunomodulators like Nrf2 activators and Akt activators may promote MARCO expression and host survival in post-influenza bacterial pneumonia, and provide effective preventive and therapeutic strategies against a common and important complication of influenza. Further elucidation of the Akt-TFEB-MARCO pathway may inform therapies to reduce susceptibility to post-influenza bacterial pneumonia.
Environmental Health

Styles APA, Harvard, Vancouver, ISO, etc.

34

Yuan, Ruoxi. « Dynamic Programming of Innate Immunity in Health and Disease ». Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/82925.

Texte intégral

Résumé :

Whether innate immune cells may be adapted into potential memory states has becoming an important question in the field of immunity. Although previous conceptual paradigm failed to acknowledge this important question, emerging clinical and basic observations have started to shed intriguing clues to shake the previous dogma regarding innate immunity of being "simple", "raw", "first-line defense with no memory". We have aimed to further address this fundamental issue in this dissertation work, under the close guidance of Dr. Liwu Li. We have chosen to use the model system of Toll-Like-Receptor (TLR) signaling networks within primary monocytes. TLRs play fundamental roles in sensing pathogen-associated molecular patterns (PAMPs) and modulation of innate immunity. Lipopolysaccharide (LPS), an endotoxin found on the cell membrane of gram-negative bacteria, is the ligand of TLR4 and induces a range of inflammatory as well as anti-inflammatory responses. Higher dosages of LPS were known to cause robust yet transient expression of pro-inflammatory mediators. On the other hand, the effects of super-low dose LPS, commonly manifested in humans with adverse health conditions, have been largely ignored in the basic research field. Super-low dose LPS may skew host immune environment into a mild non-resolving pro-inflammatory state, which is a risk factor for inflammatory diseases such as atherosclerosis, compromised wound healing, and elevated risks for sepsis. Our central hypothesize is that monocytes may be adapted by super-low dose LPS into a non-resolving low-grade inflammatory state conducive for the pathogenesis of inflammatory diseases. We have employed both in vitro cell culture system as well as in vivo disease models to test this hypothesis. For the in vitro system, we have cultured primary murine monocytes with increasing signal strength of LPS. Monocyte phenotypes such as the expression of key inflammatory mediators including cytokines, chemokines, and cellular surface markers were studied. Potential molecular and cellular mechanisms were examined. We revealed a novel low-grade inflammatory monocyte phenotype termed ML adapted by super-low dose LPS, mediated through IRF5. For the in vivo system, we have employed both acute and chronic models of inflammation. For the chronic model, we have tested the effects of super-low dose LPS on monocyte polarization in vivo, as well as its contribution to the pathogenesis of atherosclerosis. Furthermore, we have tested the effects of programmed monocytes on wound healing. For the acute model, we have tested the effects of pre-conditioning with super-low dose LPS on the subsequence risks of sepsis elicited by cecal ligation and puncture. We have demonstrated aggravated atherosclerosis, compromised wound healing, and increased sepsis mortality in mice pre-conditioned with super-low dose LPS. Taken together, our findings reveal that monocytes can be differentially programmed into distinct states, depending on the signal strength of LPS. The differential programming and adaptation of monocytes can occur both in vitro and in vivo, and may bear profound pathological consequences.
Ph. D.

Styles APA, Harvard, Vancouver, ISO, etc.

35

Carlson, Emily M. « Saponins bioactivity and potential impact on intestinal health / ». Columbus, Ohio : Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1244477535.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

36

Stzepourginski, Igor. « Identification of lymph node and intestinal lymphoid stromal cell subsets with key roles in immunity and homeostasis ». Paris 7, 2014. http://www.theses.fr/2014PA077148.

Texte intégral

Résumé :

Les cellules stromales lymphoïdes (LSCs) sont des cellules non-hématopoïétiques essentielles à l'initiation et au maintien de réponses immunitaires performantes. Caractérisées par l'expression de la podoplanine (gp38), les LSCs sont présentes à l'état basal dans les organes lymphoïdes secondaires et sont induites par l'inflammation dans tous les tissus périphériques. Dans l'intestin, les cellules exprimant gp38 constituent la majorité des cellules non-hématopoïétiques de la lamina propria. Nous avons montré que l'expression de gp38 définit une population très hétérogène de cellules aux fonctions parfois très distinctes des LSCs. Les cellules gp38+CD34- sont des myofibroblastes sous-épithéliaux situés dns les villi et spécialisés dans la différentiation d l'épithélium. Situées dans les cryptes, les cellules gp38+CD34+VCAM+ sont similaires aux LSCs des ganglions lymphatiques : elles se développent peu après le sevrage et promeuvent l'attraction et la survie des lymphocytes. En revanche les cellules gp38+CD34+VCAM- sont programmées lors du développement embryonnaire et jouent un rôle déterminant dans le maintien de l'activité des cellules souches intestinales. Afin d'identifier les précurseurs des LSCs pendant l'inflammation, nous avons développé une souris transgénique permettant de suivre la descendance des cellules exprimant le récepteur à la lymphotoxine-beta (LTβR), une protéine essentielle au développement des ganglions lymphatiques et à la maturation des LSCs. Nous avons montré pour la première fois qu'une sous-popultion de péricytes exprimant LTβR génère des LSCs dans le ganglion pendant l'inflammation
Lymphoid stromal cells (LSCs) are non-hemaopoietic cells pivotal in building and maintaining efficient immune responses. LSCs are described as podoplanin (gp38)- expressing cells and are present in secondary lymphoid organs at steady state. Moreover, LSCs are induced by inflammation and some tumors in the periphery. In the intestinal lamina propria, gp38+LSCs compose the majority of the non-hematopoietic cells at steady state. We showed that gp38+intestinal stromal cells are very heterogeneous and contain cells distinct from LSCs that populate different niches in the lamina propria. Gp38+CD34- stromal cells are subepithelial myofibroblasts located in the upper lamina propria that promote the differentiation of epithelial cells. In the crypts, gp38+CD34+VCAM+ stromal cells are the equivalent of LSCs found in lymphoid organs : they develop around weaning to attract lymphocytes into the lamina propria and promote their survival. However, gp38+CD34+VCAM- stromal cells develop during ontogeny and maintain the activity of intestinal epithelial stem cells in the crypts. In order to identify LSC progenitors during inflammation we developed a transgenic mouse model allowing for the fate-mapping of cells expressing lymphotoxin beta receptor (LTβR), a key protein involved in the development of lymphoid organs and LSC maturation. We showed for the first time that a subset of pericytes expressing LTβR give rise to LSCs during inflammation-induced expansion of the lymph node

Styles APA, Harvard, Vancouver, ISO, etc.

37

Kosinski, Cynthia. « Epithelial-mesenchymal interactions in intestinal development ». 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:3390108.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

38

Ing, Rebecca Yat Loo 1971. « Mechanisms of innate immunity to blood-stage malaria infection : role of dendritic cells in host-parasite interactions and induction of protective immunity ». Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102510.

Texte intégral

Résumé :

A favorable outcome of blood-stage malaria infection requires immune responses that effectively eliminate the infection with minimum pathology to the host. There is strong evidence that the innate immune system is critical for initiating and shaping the subsequent adaptive immune response to blood-stage Plasmodium parasites. As sentinels of infection and potent activators of immunity, dendritic cells (DCs) are pivotally positioned to control the immune response to malaria and thereby influence the outcome of infection. Experiments performed in this thesis work aimed to determine the role of DCs in host-parasite interactions and subsequent induction of protective immunity to blood-stage malaria. Moreover, the studies described herein emphasize the critical contributions of key cytokines to DC responses and interactions with other cells of the innate and adaptive immune system during blood-stage malaria. Based on previous linkage analyses that identified interleukin (IL)-15 as a candidate in genetic regulation of host resistance to blood-stage malaria, we demonstrated that IL-15 is important for timely resolution of a primary infection with Plasmodium chabaudi AS and maximal production of Th1-type cytokines and antibodies. Notably, IL-15 was revealed to be a key early cytokine for optimal DC and natural killer (NK) cell function as well as IL-12-dependent IFN-gamma production following P. chabaudi infection. Next, we demonstrated the ability of DCs to recognize and phagocytose parasitized red blood cells (pRBCs) in a highly selective and actin-dependent manner. Following interaction with pRBCs in vitro or in vivo, DCs from malaria-resistant mouse strains were shown to express upregulated costimulatory molecules and secrete abundant Th1-polarizing cytokines, particularly IL-12 and IFN-gamma. These signals enable DCs to prime other immune cells such as NK cells and CD4+ T cells for maximal IFN-gamma production. Reciprocally, malaria-activated NK cells were shown to induce DC maturation and production of Th1-polarizing cytokines, thus propagating an innate feedback loop leading to induction of Th1 immunity. DCs from malaria-susceptible A/J mice, however, showed impaired Th1 priming in favor of selective induction of IL-10-secreting CD4+ T cells, suggesting DC-mediated activation of tolerance, not immunity, in hosts unable to control and survive blood-stage malaria. These findings provide novel and important insights into the DC-mediated immune mechanisms that initiate and regulate host resistance to blood-stage malaria infection.

Styles APA, Harvard, Vancouver, ISO, etc.

39

Sugiyama, Michael. « Sex differences in the intestinal transcriptome and spatial patterns of lipid uptake capacity and intestinal lipid-metabolic gene expression ». Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107881.

Texte intégral

Résumé :

The mammalian small intestine expresses three members of the fatty acid binding protein family; Fabp1, Fabp2, and Fabp6 that differ in their spatial expression pattern and ligand binding preference. In vitro studies using recombinant FABPs suggest an important role in lipid uptake and intestinal lipid metabolism, although the in vivo functions remain unclear. Mice genetically altered to lack Fabp2 exhibit a sex-dimorphic response to high fat diet feeding featuring weight gain and fatty liver in males but not females, suggesting that Fabp2 is involved in a sex-dimorphic intestinal metabolic program. We developed a technique for the analysis of sex differences in transcriptome data and applied it to a study of the intestinal transcriptome of chow-fed Fabp2-/- mice. This analysis revealed lipid metabolic pathways that are differentially regulated in male and female Fabp2-/- mice. We next conducted a high fat diet feeding study for the purpose of analyzing the effects of Fabp2 loss on lipid uptake capacity and spatial expression patterns of lipid metabolic genes identified from the transcriptome experiment. Females lacking Fabp2 exhibited an increased capacity for lipid uptake and an increased abundance of Fabp1 mRNA in the proximal intestine. Loss of Fabp2 also caused an increased excretion of total lipids in females compared to males. This suggests that females might be protected from the adverse effects of Fabp2 loss by directing excess lipids towards excretion pathways through an intracellular, Fabp1-mediated mechanism.
Trois membres de la famille des protéines liantes d'acides gras sont exprimés dans le petit intestin des mammifères, soit le Fabp1, Fabp2 et Fabp6. Ils diffèrent par leur structuration expressive spatiale et leur affinité de ligand. Des études in vitro par recombinaison génétique suggèrent que les FABPs jouent un rôle important dans l'assimilation et le métabolisme intestinal de lipide mais leurs fonctions in vivo restent incertaines par contre. Des souris déficientes de Fabp2 par manipulations génétiques répondent différemment selon leur sexe lorsque soumissent à une diète riche en lipide de manière que les mâles subissent un gain de poids et acquièrent une hyperlipidémie du foie qui sont absents chez les femelles suggérant que le fabp2 est impliqué dans un programme métabolique intestinal dimorphe basé sur le sexe. Nous avons élaboré une technique d'analyse de données de transcriptome pour déterminer la différence sexuelle du transcriptome intestinal de la souris Fabp2-/- nourri de moulé. Cette analyse révéla que la régularisation de la voie métabolique de lipides des souris mâles diffère des femelles. Nous avons poursuivis avec une étude utilisant une diète à forte teneur en lipide dans le but d'analyser l'effet sur la capacité d'assimilation de lipide et la structuration expressive spatiale des gènes du métabolisme des lipides, identifiés par l'analyse de transcriptome précédente, par la perte de Fabp2. Les femelles déficientes de Fabp2 démontrent une augmentation de la capacité d'assimiler les lipides ainsi qu'une abondance d'ARNm de Fabp1 dans l'intestin proximal. La perte de Fabp2 cause aussi une augmentation de l'excrétion total de lipide chez les femelles lorsque comparées aux mâles. Ces observations suggèrent que les femelles semblent être protégées des effets négatifs de la perte de Fabp2 en utilisant une voie intracellulaire d'excrétion des lipides excédents. Ce mécanisme est médié par Fabp1.

Styles APA, Harvard, Vancouver, ISO, etc.

40

Bramer, Steven L. « Absorption and toxicity of drugs in intestinal tract / ». The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487779914824056.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

41

Silva, Nuno Emanuel de Oliveira Figueiredo da. « Nutrição do intestino, imunidade intestinal e resistência a parasitas do intestino em cães ». Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2009. http://hdl.handle.net/10400.5/1639.

Texte intégral

Résumé :

Dissertação de Mestrado Integrado em Medicina Veterinária
A presente dissertação é o resultado do estágio realizado na Faculdade de Ciências Agrárias e Veterinárias da Universidade Estadual Paulista “Júlio de Mesquita Filho”, Campus de Jaboticabal, São Paulo, Brasil. É composta por uma descrição resumida das actividades desenvolvidas durante o estágio, exposição breve da casuística acompanhada, seguida de uma revisão bibliográfica do tema proposto. Esta revisão incide sobre as funções do intestino na nutrição do animal e destaca o papel essencial da dieta na nutrição do intestino. Estuda-se a importância do intestino na imunidade, relacionando os mecanismos de resistência a parasitas intestinais (endo e extracelulares) em cães. No âmbito do tema escolhido, são referidos os efeitos específicos das deficiências de nutrientes a nível molecular ou de produção de citoquinas específicas. Há muitas pesquisas que demonstram que a má nutrição e a infecção ocorrem em conjunto. Não podem ser feitas generalizações sobre os efeitos de diversos nutrientes sobre os vários componentes da resposta imune, e a falta de compreensão da base de imunidade funcional contra nemátodes, torna difícil identificar as deficiências nutricionais que deveriam ser de maior preocupação. Neste estudo, o foco é centrado no intestino, que é o local da digestão e absorção de nutrientes e de permanência da maioria dos parasitas. Como complemento do tema, procede-se ao estudo dos aspectos nutricionais de sete casos clínicos acompanhados pelo autor com a respectiva discussão. Por fim, salientam-se as conclusões obtidas. Em Portugal, o autor realizou um inquérito a Médicos Veterinários sobre Nutrição Clínica, demonstrando-se que é uma área subvalorizada no nosso país. É abordada a importância de profissionais nesta área e de cursos de Nutrição Clínica para os veterinários. O tecido linfóide associado ao intestino é o maior componente do sistema imunitário do organismo. Há uma relação dinâmica entre nutrição, imunidade e doença e esta área interdisciplinar de investigação necessita de uma maior cooperação entre veterinários, parasitologistas, nutricionistas, imunologistas, biólogos moleculares e profissionais de saúde pública.
ABSTRACT - GUT NUTRITION, INTESTINAL IMMUNITY AND RESISTANCE TO INTESTINAL PARASITES OF DOGS - This thesis is the result of the training held at the Faculty of Agriculture and Veterinary Sciences, Universidade Estadual Paulista “Júlio de Mesquita Filho”, Jaboticabal Campus, São Paulo, Brazil. The description of the activities undertaken during the training, brief overview of the casuistic, followed by a literature review of the proposed theme are presented. This review focuses on the functions of the gut in animal nutrition and highlights the essential role of diet in the nutrition of the intestine. The importance of gut immunity and the relationship between mechanisms of resistance to intestinal parasites (endo and extracellular) in dogs are mentioned. As a complement of the subject, a study of nutritional aspects of seven clinical cases are referred and followed by discussion and conclusions. Considering the aim of the present work the specific effects of nutrient deficiencies at the molecular level or production of specific cytokines are highlighted. There are many studies showing that malnutrition and infection occur together. No generalizations can be made on the effects of various nutrients on the various components of the immune response. The knowledge of functional immunity basis against nematode is needed to clear identify nutritional deficiencies. In this study, the focus is centred in the intestine, an organ were absorption and digestion of nutrients as well as localization of a large number of parasites do occur. In Portugal, the author conducted a questionnaire to Veterinarians about Clinic Nutrition. The results allowed to conclude that this area is undervalued in our country and it must be taken into account the need of experts and training courses in clinical nutrition for veterinarians. The lymphoid tissue associated with the intestine is the major component of the body's immune system. There is a dynamic relationship between nutrition, immunity and disease, and this interdisciplinary research requires greater cooperation between veterinarians, parasitologists, nutritionists, immunologists, molecular biologists and public health professionals.

Styles APA, Harvard, Vancouver, ISO, etc.

42

Carrillo, Martha. « Studies on protective immunity to toxocara canis in laboratory animals / ». The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487671108307319.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

43

Murarolli, Vinicius Diogo Azevedo. « Efeito de prebiótico, probiótico e simbiótico sobre o desempenho, morfologia intestinal e imunidade de frangos de corte ». Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/10/10135/tde-23012009-133435/.

Texte intégral

Résumé :

A possível indução de resistência bacteriana devido a inclusão de antibióticos, e a pressão dos consumidores por produtos de qualidade, levaram a proibição do uso dos mesmos na alimentação animal. Diante destes acontecimentos, as buscas por alternativas como os prebióticos, probióticos e simbióticos em substituição aos antibióticos vêm sendo bastante enfatizados na alimentação animal pois, estes, além de proporcionarem uma modulação benéfica da microbiota intestinal, atuam na diminuição do estresse imunológico. Portanto, o presente estudo teve como objetivo verificar a influencia de prebiótico, probiótico e simbiótico sobre o desempenho, morfologia intestinal e imunidade de frangos de corte em substituição ao antibiótico. Foram utilizados 1400 pintos de corte, criados até 42 dias de idade, em um delineamento inteiramente casualizado, com 5 tratamentos: Controle; Probiótico; Prebiótico; Simbiótico (prebiótico + probiótico); Antibiótico, 7 repetições/tratamento com 40 aves cada. Quanto ao desempenho, considerando o período total de criação e nas condições em que o experimento foi conduzido, não foi possível mostrar influência dos aditivos testados nos parâmetros zootécnicos avaliados. Já para imunidade, observou-se um efeito de prebiótico para resposta vacinal contra a doença de Newcastle aos 28 dias e um efeito de prebiótico para peso relativo de baço. Com relação à morfologia intestinal observou-se que o probiótico, quando adicionado à dieta, apresentou uma menor altura de vilo de jejuno e um efeito de interação de forma antagônica para altura de vilo do íleo. Além disso, no parâmetro de profundidade de cripta, verificou-se um efeito de interação de forma antagônica para o duodeno e um efeito de probiótico no jejuno, sendo que o probiótico, ao ser adicionado à dieta apresentou menor valor. Por fim a presença de prebiótico na dieta aumentou o número de células caliciformes tanto no duodeno como no jejuno.
The market pressures, since consumers require products with high quality, and the possible inducement for the bacterian resistance due to the inclusion of antibiotics as well, have caused the prohibition of the referred antibiotics in animal alimentation. Considering this event, alternatives like prebiotics, probiotics and symbiotics have been emphasized in animal alimentation because they provide intestinal microbiota benefits and less immunologic stress. Therefore, this study evaluated the influence of prebiotic, probiotic and symbiotic in broiler performance, as well as in their intestinal morphology and immunity in antibiotics replacement. 1400 day-old broiler chicks were used during 42 days, in a randomized block design, with 5 treatments: Control, Probiotic, Prebiotic, Symbiotic (prebiotic + probiotic) and Antibiotic. There were 7 repetition with 40 chicks each. Regarding the performance, there was no influence from the tested additives, considering the zoothecnics parameters studied. Considering the immunity, there was a prebiotic effect for the antibodies response against Newcastle disease on the 28th day, and a prebiotic effect to the spleen weigh. Regarding the intestinal morphology, it was observed that when the probiotic was added to the diet, it showed a shorter jejunum villus and an antagonic interaction effect for ileum villus height. Besides, there was antagonic interaction effect for the duodenum crypt depth and a probiotic effect in the jejunum. Still considering the jejunum, it was observed that when the probiotic was added to the diet, it shows lower results. The prebiotic presence in the diet also shows the increase of the caliciform cells number in both duodenum and jejunum.

Styles APA, Harvard, Vancouver, ISO, etc.

44

Junior, Andrés Jimenez Galisteo. « "Toxoplasma gondii vs radiação ionizante : Estudo da imunidade intestinal em camundongos C57Bl/6j experimentalmente vacinados com taquizoítos irradiados" ». Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-05072004-095512/.

Texte intégral

Résumé :

Em nosso estudo pretendemos estudar a via oral para o desenvolvimento de vacina para toxoplasmose utilizando parasitas irradiados por Cobalto-60, como uma alternativa para a prevenção desta importane parasitose. Para tanto, avaliamos o desenvolvimento da imunidade sistêmica e intestinal e a resistência à infecção, em camundongos imunizados por esta via com taquizoítos irradiados a 255Gy, e desafiados com cistos da cepa ME-49. Camundongos isogênicos C57Bl/6j foram imunizados com 107 taquizoitos de T. gondii irradiados a 255Gy em diferentes esquemas e utilizando adjuvantes leite (anti-péptico) e hidróxido de alumínio (anti-ácido). As preparações de taquizoítos irradiados por via oral induziram produção de imunoglobulinas IgG e IgA no soro de camundongos, sendo predominante a subclasse de IgG2a, similar a infecção crônica, determinadas por ELISA. Seu uso com adjuvantes anti-pépticos ou anti-ácidos induziu produção de IgA fecal e menos significativamente de IgG fecal. Existem indícios de indução de tolerância em nível intestinal, com queda da produção de anticorpos e da proliferação celular antígeno dirigida, especialmente quando o leite foi utilizado como adjuvante, em ensaios de produção in vitro de anticorpos ou proliferação estimulada por antígenos de T.gondii, por esplenócitos e linfócitos intestinais. As preparações orais induziram proteção quantitativa ao desafio dos animais imunizados por cepa cistogênica, que foi semelhante a imunização parenteral, quando o hidróxido de alumínio foi usado como adjuvante. Todos estes dados mostram a possibilidade de desenvolvimento de uma vacina oral para toxoplasmose utilizando taquizoítos irradiados, com aplicação prática num futuro próximo para uso em campo, utilizando iscas atrativas para imunizar felinos domésticos e selvagens.
We study the oral route for the development of a vaccine for toxoplasmosis, using parasites irradiated with 60 Cobalt, as an alternative for vaccine development to this worldwide parasitic infection. We evaluated the development of immunity at serum or mucosal levels, and their efficiency in protect the mice against challenge with oral cysts of the ME-49 strain. C57Bl/6j isogenic mice were immunized by oral route with 107 255 Gy irradiated tachyzoites from RH strain, at several protocols using milk as anti-peptic adjuvant and alum hydroxide as antacid. The preparations of irradiated tachyzoites induced production of serum IgG and IgA in immunized mice, as determined by ELISA, with IgG2a as the dominant subclass, similar to chronic infection. Their use with adjuvant allowed the excretion of significant amounts of IgA in stools also IgG, despite a lesser extent. There are suggestion of tolerance induction at mucosal level, with lower antigen induced proliferation and lower in vitro antibody production by spleen and gut lymphocytes, with the latter doses, specially when milk was used as adjuvant. All oral preparations induced some quantitative protection against challenge, which was similar to the parenteral route only isolated alum hydroxide was used as adjuvant. All these data support the possibility of the development of an oral vaccine against toxoplasmosis, using irradiated tachyzoites, which would be possible tool in near future for use in field baits, for immunizing either domestic or wild felids.

Styles APA, Harvard, Vancouver, ISO, etc.

45

Bertsche, Joseph. « Histone Deacetylase Inhibitors and Innate Immunity in Septic Shock ». VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/2011.

Texte intégral

Résumé :

Innate immunity depends on pattern recognition receptors, which recognize pathogen associated molecular patterns (PAMPS), such as Toll-like receptor 4 (TLR4), which detects the gram-negative bacterial toxin, lipopolysaccharide. Engagement of TLR4 by LPS sets off a cascade ending in the activation of pro-inflammatory cytokines and interferon-β (IFN-β) which alerts the host to the infection. However, these responses can be mal-adaptive, especially in the context of bacterial sepsis, where a "cytokine storm" results in death of the host. Pharmacological modulation of these responses may therefore be a promising treatment modality. Inhibition of classic pro-inflammatory cytokines such as IL-1β and TNF-α has been the (largely unfruitful) focus of much research. However it has recently emerged that mice with defects in type I IFN signaling are also substantially resistant to challenge with endotoxin. We therefore wish to investigate pharmacological inhibition of IFN signaling as a potential means to control sepsis. We analyzed the effects of Trichostatin A (TSA) and Suberoylanilide hydroxamic acid (SAHA) (both broad spectrum HDAC inhibitors) and ST-2-92 (HDAC6 specific inhibitor) on IFN regulation and endotoxic shock. We created an in vivo mouse model for this treatment with TSA and SAHA (which are well tolerated in mouse and human) to look for possible alteration in the survival rate following endotoxin challenge. We as well as others found that treatment with SAHA (50mg/kg) significantly improves survival rate. We also characterized in-vitro modulation of IFN responses through SAHA by mouse DNA microarray. We noticed a decreased expression of many innate immune regulated genes in the SAHA and LPS treated condition compared to the LPS treatment alone. Additionally we observed a decrease in protein levels of IFN-β IL-1β, IL-6, IL-12p40, RANTES and TNF-α in cell culture supernatants treated with SAHA or ST-2-92 and LPS compared to LPS only treatment. These results show the ability of broad spectrum HDACi through SAHA to increase mouse survival following LPS challenge as well as modulate the induction of innate immune responsive genes in vitro. Furthermore we have shown that HDAC specific inhibition through ST-2-92 can decrease pro-inflammatory transcript as well as protein levels.

Styles APA, Harvard, Vancouver, ISO, etc.

46

Kellman, Maxine Franchestcê. « Development of an antigen-specific ELISPOT to detect intestinal antibody responses to the swine whipworm, Trichuris suis ». Diss., Virginia Tech, 1997. http://hdl.handle.net/10919/39493.

Texte intégral

Résumé :

The swine whipworm, Trichuris suis, is a parasite present throughout the United States and is of concern to the swine industry worldwide because it is very pathogenic to growing pigs. The economic threat posed by T. suis and other intestinal parasite infections has created a strong interest in the development of parasite vaccines for the swine industry. Use of a vaccine either alone or with anthelmintics should reduce the economic losses. However, before effective parasite vaccines can be created, the swine gastrointestinal immune response to parasite antigens must be understood. In this study, an enzyme-linked immunospot (ELISPOT) assay was developed to measure total and antigen-specific IgG and IgA antibody secreting cells (ASC) from gut-associated lymphoid tissues (GALT) [mesenteric lymph node explants from jejunal region of small intestine (SI-MLN) and cecum in large intestine (C-MLN); and ileocecal Peyer's patches (IC-PP)] and lamina propria from the proximal colon removed from T. suis infected pigs. Tbe local antibody responses were compared to peripheral antibody responses found in the spleen and submandibular lymph nodes. The hypotheses to be tested was that parasite antigen-specific antibody secreting cells would be greatest in lymphoid tissue draining the site of infection compared to peripheral lymphoid tissues and that 19A ASC would predominate over IgG ASC in the lamina propria of T. suis infected pigs. The total IgG and IgA ASC frequencies for the spleen, SI-MLN, and ICPP did not significantly change (P> 0.05) over time. For C-MLN, there was a significant increase (p< 0.05) of total IgG ASC during a primary infection with T. suis. Antigen-specific IgG ASC were greatest at the GALT site closest to the infection, CMLN, whereas, antigen-specific IgA ASC predominated in the proximal colonic: lamina propria. Host protection to T. suis develops after anthelmintic: treatment of a primary exposure to parasite. The ELISPOT assay provided valuable information on the localization and compartmentalization of the swine gastrointestinal immune response to T. suis which resides in the cecum and proximal colon. In the future, this technique may be useful for monitoring gastrointestinal immune parameters of pigs exposed to a T. sllis vaccine.
Ph. D.

Styles APA, Harvard, Vancouver, ISO, etc.

47

Hsieh, Hsiang Chuan. « Checkpoint modulation of T cell immunity by novel fusion cytokines ». Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121154.

Texte intégral

Résumé :

Functional immunity requires a balanced T cell immune response, which entails the maintenance of de novo production (i.e. TCR repertoire diversity) and the appropriate differentiation of effector subsets at the periphery. However, numerous pathogenic changes can perturb this homeostasis. On the one hand, diminished thymopoiesis or exhausted effectors cause immune dysfunction, leading to the persistence of virally infected or cancerous cells. Unrestrained immune reaction, on the other hand, can cause significant tissue damage. The main objective of my thesis therefore was to develop novel therapeutics to modulate T cell immunity in the context of cancer and inflammatory diseases. Interleukin-7 (IL7) is critically involved in T cell development and homeostatic proliferation. In order to pharmacologically induce T cell neogenesis for immune reconstitution and cancer therapy, we developed a novel biopharmaceutical based on the fusion of GMCSF and IL7 (GIFT7). GIFT7 administration in aged mice led to cortical hyperplasia, effectively reversing tissue involution. GIFT7-mediated hypertrophic effect includes an increase in total thymic cellularity and more importantly a 4-fold increase in the number of CD4-CD8-CD44intCD25-early thymic precursors. In the periphery, GIFT7 selectively expand a CD8+subset from pre-activated T cells with a phenotype defined as CD8+CD44+CD62L+CCR7+KLRG-CD27+, hereafter TGIFT7. The adoptive transfer of OTI-derived CD8 TGIFT7 into OVA-EG7-bearing mice leads to significant tumor regression. Furthermore, the human ortholog of GIFT7 (hGIFT7) leads to a two-fold increase in total cell number after 3 days and >80% of Ki67+expression in both CD4+ and CD8+ PBMC with concurrent reduction in PD1 expression, the cardinal marker of T cell exhaustion. Therapeutically, augmented T cell immunity via GIFT7 delivery rescues mice from disseminated leukemia. On the opposite spectrum of hypofunction, self-directed T cell over-reaction also demands therapeutic intervention. We have previously shown N-terminal modified(tetra-peptide-cleaved) MCP3 possessed immune suppressive activity. In view of this, we hypothesized that a synthetic cytokine linking GMCSF to MCP3 (GMME3) as part of a single polypeptide would augment its immune plasticity. We demonstrated that GMME3 induces significant Ca++ influx, activating IL10+CD21hiCD24hi CD1.dhi subset of splenic B cells (BGMME3) capable of inhibiting antigen presentation and Th17. The adoptive transfer of BGMME3 to mice symptomatic with experimental autoimmune encephalitis attenuated disease progression. Overall, the research presented in this thesis supports the use of GMCSF-based fusion cytokine as novel immune regenerative and modulatory therapeutics to (i)augment thymopoiesis, (ii) promote effector expansion, (iii) and regulate helper polarization. Therefore, our work points to the translational potential of fusion cytokines or fusion-primed immune cells as treatment of T cell dysfunction.
L'immunité fonctionnelle des lymphocytes T exige le maintien de la diversité de répertoire et la différenciation appropriée des sous-ensembles à la périphérie. Cependant, les nombreux changements pathogènes peuvent perturber cette homéostasie. D'une part, la diminution de thymopoïèse ou l'épuisement des effecteurs provoquent un dysfonctionnement immunitaire, conduisant à la persistance des cellules infectées par des virus ou des cellules cancéreuses. Une réaction immunitaire effrénée peut, d'autre part, endommager les tissus. Le principal objectif de ma thèse était donc de développer de nouvelles thérapies pour moduler l'immunité des cellules T dans le contexte du cancer et des maladies inflammatoires. L'interleukine-7 (IL7) est particulièrement importante dans le développement des cellules T et sa prolifération homéostatique. Afin d'induire pharmacologiquement la néogenèse des cellules T, pour la reconstitution immunitaire et le traitement du cancer, nous avons développé un produit biopharmaceutique basé sur la fusion de GM-CSF et IL7 (GIFT7). L'administration de GIFT7 à des souris âgées a conduit à une hyperplasie corticale, inversant efficacement l'involution des tissus. L'effet hypertrophique du GIFT7 provoque une augmentation de la cellularité thymique totale et surtout une multiplication par 4 du nombre de CD4-CD8-CD44intCD25-précurseurs thymiques. Dans la périphérie, GIFT7 provoque la prolifération sélective d'un sous-ensemble CD8+ avec un phénotype défini comme CD8+CD44+CD62L+CCR7+KLRG-CD27+ (TGIFT7). Le transfert adoptif de cellules CD8 dérivée OTI-TGIFT7 dans l'OVA-EG7 des souris porteuses conduit à une régression tumorale significative. En outre, l'orthologue humain de GIFT7(hGIFT7) conduit à une multiplication par deux du nombre de cellules total après 3 jours et > 80% de Ki67+ expression dans les deux CD4+ et CD8+ PBMC avec réduction concomitante de PD1 expression, qui est le marqueur cardinal de l'épuisement des cellules T. L'augmentation de l'immunité des cellules T, via la livraison de GIFT 7, sauve les souris de leucémie diffusée. Sur le spectre opposé d'hypofonction, la sur-réaction de l'auto-cellule T exige également une intervention thérapeutique. Nous avons montré précédemment que le N-terminal modifié (tétra-peptide clivé) MCP3 possédait une activité immunitaire suppressive. Compte tenu de cela, nous avons émis l'hypothèse qu'une cytokine GM-CSF synthétique liée au MCP3 (GMME3) dans le cadre d'un polypeptide unique permettrait d'accroître sa plasticité immunitaire. Nous avons démontré que le GMME3 induit significativement Ca++ afflux, l'activation de l'IL10+CD21hiCD24hiCD1.dhi sous-ensemble de cellules B spléniques (BGMME3) capables d'inhiber la présentation de l'antigène et Th17. Le transfert adoptif de BGMME3 a atténué la progression de la maladie auto-immune de souris présentant des symptômes d'encéphalite expérimentale. Dans l'ensemble, la recherche présentée dans cette thèse soutient l'utilisation de la fusion pour la régénération immunitaire et de la thérapeutique modulation de (i) lathymopoïèse, (ii) l'expansion effecteur, (iii) et de la polarisation d' CD4+. Nos points de travail concernent le potentiel de translation de cytokines de fusion ou de fusion-apprêtées cellules immunitaires pour le traitement de la dysfonction des cellules T.

Styles APA, Harvard, Vancouver, ISO, etc.

48

Pietz, Grzegorz. « Innate immunity of human intestinal epithelium in childhood celiac disease : influences from celiac disease associated bacteria and dietary oats ». Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-140691.

Texte intégral

Résumé :

Background & Aims: Celiac disease (CD) is a chronic inflammatory small-bowel enteropathy caused by permanent intolerance to gliadin in wheat gluten, and related proteins in ray and barley. It is disputed whether CD patients tolerate oats. The only treatment of CD is lifelong gluten-free diet (GFD). Only individuals that carry the HLA-DQ2 and/or DQ8 alleles, and eat gluten can develop CD. Dysbiosis in the gut microbiota is a suggested risk factor for CD. T cells in small intestinal mucosa, including intraepithelial lymphocytes (IELs), are known to be important in the pathogenesis of CD. In contrast, the role of intestinal epithelial cells (IECs) is poorly understood. In this thesis we investigated the role of IECs in the immune pathology of CD from duodenal mucosa of children with CD, clinical controls and treated CD. We also investigated the role of CD associated bacteria and oats supplemented GFD on the mucosal immune system. Results: A new CD-associated bacterium, Prevotella jejuni, was isolated and characterized. It is a saccharolytic and proteolytic anaerobe. More than 25 defense-related genes, including IRF1, SPINK4, ITLN1, OAS2, CIITA, HLA-DMB, HLA-DOB, PSMB9, TAP1, BTN3A1, and CX3CL1, were upregulated in IECs in active CD. In two in vitro models for intestinal epithelium, small intestine enteroids and T84 polarized tight monolayers, we showed that 70% of these genes were upregulated by interferon (IFN)-γ via the IRF1 pathway. IRF1 was also upregulated by the CD-associated bacteria P. jejuni and Actinomyces gravenitzii. IECs expressed the NLRP6/8 inflammasome yielding CASP1 and biologically active interleukin (IL)-18, which induces IFN-γ in IELs. P. jejuni bound the intestinal epithelial cell lines T84, Caco2, HT29, and INT407, while Lachnoanaerobaculum umeaense preferentially bound Caco2. P. jejuni caused decreased transepithelial resistance over tight monolayers, while L. umeaense caused an increase. P. jejuni upregulated mRNAs for the detoxification molecules CYP1A1, CYP1A2, CYP1B1, and TIPARP, the chemokines CX3CL1, CXCL1, and CXCL10, the sialyltranserase ST3GAL4, and the inflammation promoting protein S100A3 in tight monolayers. L. umeaense upregulated the chemokines CCL20 and CXCL10, and down-regulated TLR2. In a randomized, double-blinded intervention trial comparing two study-groups, standard GFD and oat-containing GFD, we found that mRNAs for several immune effector molecules and tight junction proteins were only reduced in patients receiving GFD, but not in a substantial fraction of patients on GFD with oats. The down-regulatory cytokines IL-10 and TGF-β1, the cytotoxicity-activating NK-receptors NKG2C and NKG2E, and the tight junction protein claudin-4 remained elevated in the study group on GFD with oats. Conclusions: IECs are far from inactive in CD. A key factor in the epithelial reaction in CD appears to be over-expression of IRF1 in IECs. Dual activation of IRF1 and IRF1-regulated genes, both directly by P. jejuni and indirectly by IFN-γ via the IL-18-inflammasome, would drastically enhance the inflammatory response and lead to the pathological situation seen in active CD. P. jejuni harms the intestinal epithelium, i.e., it is a likely risk factor for CD, while L. umeaense strengthen barrier function and local immunity, possibly acting as a protective. A fraction of CD patients should avoid oats in the diet.
Doctoral thesis

Styles APA, Harvard, Vancouver, ISO, etc.

49

Patrick, Christopher. « Cereal Induced Autoimmune Diabetes is Associated with Small Intestinal Inflammation, Downregulated Anti-Inflammatory Innate Immunity and Impaired Pancreatic Homeostasis ». Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/30391.

Texte intégral

Résumé :

Background: Intestinal inflammation elicited by environmental determinants including dietary proteins and microbes is implicated in type 1 diabetes (T1D) pathogenesis. Also, intrinsic pancreatic abnormalities could precede classic insulitis, contributing to T1D. Materials and Methods: Spontaneous rat T1D models were used for in situ analyses of gut and pancreas to explore novel disease pathways using immunohistochemistry and detailed morphometry, gene expression studies, and molecular screening analyses. Results: In BBdp rats, feeding a cereal diet stimulated T1D under germ-free or specific pathogen-free (SPF) conditions compared with a protective hydrolyzed casein (HC) diet. Cereal-induced T1D was paralleled by increased gut T cell infiltration and TH1-associated pro-inflammatory transcription. HC-fed rats displayed an increased number of anti-inflammatory CD163+ M2 macrophages compared with cereal-fed rats. Cereal-associated promotion of T1D in Lewis diabetes-prone (LEW-DP) rats, a different rat model, similarly featured gut T cell infiltration in conjunction with decreased immunoregulation. The Camp gene was induced in diet-protected HC-fed BBdp rats. Camp encodes the cathelicidin antimicrobial peptide (CAMP), a pleiotropic immunomodulatory host defence factor. Intestinal CAMP was enriched in CD163+ M2 macrophages and could represent a novel marker of these tolerogenic innate immune cells. CAMP expression was also discovered in pancreatic lymph nodes (PLN) and islets, indicating a novel role for this factor in target tissue homeostasis. There was a positive correlation between pancreatic CAMP and total islet number. Also, islet-associated CAMP+ cells were increased in rats with islet inflammation, suggesting upregulation in parallel with insulitis. Exogenous CAMP/LL-37 injections increased the abundance of T1D-protective probiotic bacteria and promoted islet neogenesis in BBdp rats. A prospective partial pancreatectomy (PPx) study was performed to obtain pre-diabetic pancreas biopsies from iii pre-insulitic BBdp rats. The number of endothelium-associated CD68+ macrophages was increased in pre-diabetic pancreata, indicating that perivascular inflammation was an early lesion in the animals. In addition, pre-diabetic pancreata featured enhanced regenerative Reg3a and Reg3b gene expression, indicating abnormal islet expansion preceding insulitis. Conclusions: Small intestinal inflammation paired with deficits in local immunoregulation parallels T1D development. CAMP represents a novel factor in T1D that could have several pleiotropic functions including regulation of commensal microbes, intestinal homeostasis, and pancreatic homeostasis. In addition, target tissue abnormalities precede insulitis and T1D. This research focused on the integrative biology of T1D pathogenesis in spontaneous rat models. This work provides a novel working model that incorporates key roles for gut lumen antigens, intestinal immunity, and the role of islets and altered regenerative capacity in T1D. This research could lead to new therapeutic opportunities for T1D treatment.

Styles APA, Harvard, Vancouver, ISO, etc.

50

Abou, Samra Elias. « Elucidation of the Role of NKR‐P1 : CLR Recognition Systems in Intestinal & ; Renal Epithelial Cell Homeostasis and Immunity ». Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35747.

Texte intégral

Résumé :

Natural killer (NK) cells represent a crucial component of the innate immune system and are primarily regulated by the interactions of their activation and inhibitory receptors with ligands available on target cells. The genetically linked Ly49 and NKR-P1 family of receptors constitute two of the major regulatory receptor systems used by NK cells and have been shown to bind different ligands. Whereas the Ly49 receptors survey MHC-I ligands on target cells, the NKR-Pl receptor family members bind to various members of the C-type lectin-related (Clr) family. Interestingly, NKR-P1 and Clr haplotypes possess a stable genomic polymorphism across multiple mouse strains, suggesting that this inhibitory receptor:ligand relationship has an important role in the maintenance of host cellular cognate specificities. The NKR-P1 and Clr receptor-ligand pairs identified in mice include the NKR-P1B:Clr-b and the NKR-P1G:Clr-f interacting pairs. Previous RT-PCR and in situ RNA hybridization data generated by our laboratory determined that kidney tubular epithelium as well as the small and large intestinal epithelial cells specifically and highly expresses the Clr-f transcripts. Contrarily, the Clr-b transcripts were only detected on hematopoietic cells of various lymphoid organs and kidneys. Moreover, foregoing studies revealed that the loss of Clr-b following viral or chemical induced stress mediates NK cell killing of the target cell, suggesting a tissue-specific immune-surveillance mechanism in parallel with the global MHC-I-dependent missing-self model. However, the role of the NKR-P1B:Clr-b recognition-system have never been examined in the intestine. Additionally, the role of Clr-f in the kidney and intestines, where they are highly expressed, has not been investigated. For these reasons, I aimed in my thesis to provide a better understanding of the functional aspect of the NKR-P1B:Clr-b and NKR-P1G:Clr-f recognition systems in mediating gut mucosal and renal homeostasis, respectively. First, in order to determine the role of NKR-P1B and Clrb receptor:ligand pair as a “missing-self” immunosurveillance system in the gut, I started by identifying the expression pattern of both the receptor and ligand on various intestinal cells. My results demonstrate that NK cells do not represent the major NKR-P1B-expressing cells in the gut lamina propria. Instead, ILC3 subsets constituted the predominant cell population expressing the receptor, whereas γδT cells composed a small fraction of NKR-P1B+ lymphocytes. In addition, the NKR-P1B expression on myeloid cells was exclusive to colon macrophages and DC subsets. Interestingly, the highest percentage of NKR-P1B+ immune cells was found in the gut, which suggests the dominant role of NKR-P1B in regulating immune functions at the level of intestinal mucosa. As expected, the expression of the NKR-P1B ligand, Clr-b, appeared on all innate immune cell types in the gut. Next, using oral infection models of Salmonela typhimurium and Citrobacter rodentium, I showed that NKR-P1B-deficient NK cells, ILC3 and γδ T cells are hyporesponsive compared to their WT counterparts. In particular, gut NKR-P1B-deficient NK cells and γδT cells secreted low levels of IFNγ cytokine while infected with S.typhimurium. Importantly, the decreased IFNγ secretion by NK and γδT cells was associated with an increased dissemination of the bacterium into the knockout spleens at day 5 post-infection. Likewise, I detected a significant decrease in IL-22 cytokine production by NKR-P1B-deficient ILC3 compared to their WT counterparts at both steady state and following C.rodentium infection. Next, I address the potential role of Clr-f in the kidney. Renal tubular epithelial cells have been shown to express high levels of Clr-f transcripts. Epithelial cells constitute the major cellular component of kidney tubules and are well known to mediate metabolic waste excretion, reabsorption of essential molecules as well as other physiological functions, such as ions exchange and water retention. To determine the role of Clr-f in renal epithelial cells, I generated a Clr-f-deficient mouse with the help of two of my previous lab colleagues. Importantly, chemical analysis on urine and serum samples from knockout and WT littermates indicated that Clr-f-deficient kidneys display a decreased filtration capacity. In particular, higher creatinine levels were detected in the Clr-f deficient serum. In addition, Clr-f-deficient mice appeared to have a lower fractional excretion of sodium (FENa) in their urine filtrates in comparison to WT excreted urine. Blood pressure measurements on the same mice at 12 and 24 weeks of age revealed a hypotensive phenotype in the Clr-f-deficient mice. Furthermore, pathological assessment of Clr-f-deficient kidneys exhibited moderate and aggravated lesions of the tubular epithelium along with marked glomerular mesangiolysis. Lastly, flow cytometry analysis on isolated lymphocytes from Clr-f-deficient and WT mice demonstrated comparable immune infiltrates between the two mouse genotypes. Altogether, our data shows that the absence of Clr-f results in the development of glomerular and tubular lesions in an immune-independent manner leading to an abnormal kidney function. Additionally, the disruption of NKR-P1B:Clr-b recognition system results in abnormal innate immune cell number and function in the mouse intestine. These novel findings sheds light on the important role of Clr-f in maintaining healthy kidney morphology and function, as well as the crucial role for NKR-P1B:Clr-b interactions in mediating intestinal homeostasis at steady and infected states.

Styles APA, Harvard, Vancouver, ISO, etc.

Thèses sur le sujet « Intestinal Health and Immunity »

Créez une référence correcte selon les styles APA, MLA, Chicago, Harvard et plusieurs autres