Dissertations / Theses: 'Immunology; Cytokines'

1

Palmblad, Karin. "Cytokines and cytokine-directed intervention in experimental arthritis /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4589-6/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Ghorayeb, Christine. "The regulation of human B cell effector cytokine profiles by exogenous T helper cell cytokines /." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111556.

Full text

Abstract:

The Bar-Or laboratory recently reported that human B cells from normal subjects can produce either pro-inflammatory (TNF-alpha; LT) or regulatory (IL-10) effector cytokines depending on their context of activation. It was of interest to investigate the change in B cell cytokine profiles from normal subjects when activated in the context of a Th1 pro-inflammatory environment or a Th2 anti-inflammatory environment. It was found that the B cell regulatory network of effector cytokines from normal subjects is significantly modulated depending on the local cytokine milieu. In addition, it was of interest to study how MS patients' B cell cytokine network would respond in a Th1 pro-inflammatory and a Th2 anti-inflammatory context. It was found that MS patients' B cell cytokine network was dysregulated compared to B cell responses from normal subjects. The findings define a novel regulatory network involving human B cells from normal subjects and point to a newly discovered abnormality in MS patients' B cells.

APA, Harvard, Vancouver, ISO, and other styles

3

Ulfgren, Ann-Kristin. "Cytokines in rheumatoid arthritis /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-3823-7/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Mundy-Bosse, Bethany L. "Myeloid-Derived Suppressor Cells in Tumor Immunology." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1311261626.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Ahmed, Ahmed Abdelaziz. "Neuroimmune interaction in cutaneous leishmaniasis /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980925ahme.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Diab, Asim Eltayeb. "Experimental bacterial meningitis : studies on immunopathogenesis and immunoregulation /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3008-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

7

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.

Full text

Abstract:

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.

APA, Harvard, Vancouver, ISO, and other styles

8

Williamson, Eilidh. "Cytokines in the immunopathogenesis of murine graft-versus-host disease." Thesis, University of Glasgow, 1997. http://theses.gla.ac.uk/40906/.

Full text

Abstract:

Murine models of graft-versus-host disease (GvHD) provide important information relevant to clinical bone marrow transplantation (BMT), as well as to other types of T cell-mediated pathology. The nature of the GvHD which develops in (C57BL/6 X DBA/2)F1 (BDF1) mice injected with parental lymphocytes is dependent on whether C57B1/6 (B6) or DBA/2 parental donor cells are used. BDF1 mice injected with B6 donor cells (B6 => BDF1) develop an acute GvHD with early lymphoid hyperplasia and NK cell activation, followed by immunosuppression, activation of anti-host cytotoxic T lymphocytes (CTL), weight loss and early death. In contrast, BDF1 mice given DBA/2 donor cells (DBA/2 => BDF1) exhibit a chronic, stimulatory GvHD, characterised by B cell hyperreactivity, autoantibody production and immune complex-mediated glomerulonephritis (ICGN). Previous studies have shown that the distinct forms of GvHD in BDF1 recipient mice are associated with different patterns of cytokine production. Whereas acute GvHD is characterised by production of high levels of Th1 cytokines, chronic GvHD is associated with a preferential Th2 response. Therefore, it was suggested that the two forms of GvHD may reflect differential activation of distinct subsets of CD4+ T helper (Th) cells. However, when and why such T cell polarisation should occur has remained unclear. A number of recent studies have demonstrated that cytokines produced by cells of the non-specific immune system during the early phase of an immune response can strongly influence the type of specific response which develops subsequently. The main aim of this thesis was to explore the role of these early immune mediators in determining the outcome of the GvHD in BDF1 mice. These studies of the cellular and molecular interactions involved in murine GvHD have implications for understanding the pathogenesis of clinical GvHD and the development of specific therapy following BMT. In addition, they provide an important insight into the regulation of immune responses during other immunologically-mediated diseases.

APA, Harvard, Vancouver, ISO, and other styles

9

Barkhuizen, Mark. "Determination of the role of cytokines using gene deficient mice in African trypanosomiasis infection." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3119.

Full text

Abstract:

Includes bibliographical references.
African trypanosomiasis encompasses diseases caused by pathogenic trypanosomes, infecting both humans and animals alike. To determine the immunological role of IL=12 family members in Trypanosoma brucei brucei, Trypanosoma evansi and Trypanosoma congolense infections, IL-12p35¯/¯, IL-12p40¯/¯ and IL-12p35¯/¯/p40¯/¯ mice were used. While the two latter mouse strains lack all IL-12 homologues, IL-12p35¯/¯ mice still produce IL-12p80 homodimers and IL-23. In infection with T.b. brucei and T.evansi; IL-12p35¯/¯, IL-12p40¯/¯ or IL-12p35¯/¯/p40¯/¯ mice were susceptible to both these pathogens, demonstrated by increased mortality compared to wild type C57BL/6 mice. The different IL-12 deficient mouse strains showed similar mortality kinetics, suggesting that IL-12p70 but not the IL-12p80 homodimer or IL-23 plays a crucial role in survival. Similarly, parasitemia control was reduced in the absence of IL-12p70. While plasma levels of IgM and IgG2c were similar between IL-12 deficient mice and wild type mice, IF-γ production. As IFN-γR¯/¯ mice were also highly susceptible to both T.b. brucei and T. evansi, IL-12p70-dependent IFN-γ production seems to be important mechanism involved in resistance against both these pathogens.

APA, Harvard, Vancouver, ISO, and other styles

10

Alshehri, Ali Awadh. "Cell Viability, Cytoskeleton Organization and Cytokines Secretion of RAW 264.7 Macrophages Exposed to Gram-Negative Bacterial Components." Wright State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1481857962791924.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Vallabh, Sushmitha. "Targeted Epigenetic Suppression of Th2 Cytokines Expression." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505131225205869.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Parker, Ruth E. "The rat interleukin-4 receptor." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318893.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Gonzalez, Henrik. "The post-polio syndrome : studies of immunology and immunomodulatory intervention /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-483-X/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Spearman, C. W. N. "Orthotopic liver transplantation at Groote Schuur Hospital : a serial analysis of biliary cytokines and biochemical parameters." Master's thesis, University of Cape Town, 1991. http://hdl.handle.net/11427/25952.

Full text

Abstract:

Orthotopic liver transplantation is the treatment of choice for many patients with end-stage liver disease. Despite advances in immunosuppression, acute rejection remains common (up to 70%) and results in significant patient morbidity. It is frequently difficult to distinguish abnormal liver function due to rejection from that due to infection, biliary obstruction or ischaemic injury without performing invasive procedures such as a liver biopsy or angiography which may be Clinically, the diagnosis of rejection is usually once the immunological process is already hazardous. made late, established. In this study, we evaluated standard biochemical parameters and cytokine concentrations (IL-1, IL-6 and TNF-alpha) in serial samples of bile obtained post-operatively via the Ttubes of patients following orthotopic liver transplantation in order to determine whether there are any biochemical or immunological pointers to the early diagnosis of rejection which would enable earlier administration of appropriate antirejection therapy. Biliary cytokines did not prove to be useful and reliable markers of early rejection. Serial measurement of biliary bilirubin levels showed an early and significant decrease a few days prior to rejection, and were a more sensitive marker of graft function than serum bilirubin levels.

APA, Harvard, Vancouver, ISO, and other styles

15

Mathsson, Linda. "Immune Complex Regulated Cytokine Production in Rheumatic and Lymphoproliferative Diseases." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7446.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Stein, Michael. "Regulation of the secretory and endocytic activities of murine macrophages by T lymphocyte-derived cytokines." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315870.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

El-Maghraby, Nermine Mostafa. "Modulation of BLT1 expression in human NK cells by selected cytokines." Mémoire, (Accès réservé UdeS) Droit de reproduction illimitée uniquement pour la création de matériel didactique, 2007. http://savoirs.usherbrooke.ca/handle/11143/3894.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

MacPherson, Alexandrea. "Production and role of IL-17 and related cytokines in response to respiratory pathogens." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3543/.

Full text

Abstract:

Background: Pneumonia is a disease of the lungs that is caused by a number of pathogens including Gram-negative Pseudomonas aeruginosa and Gram-positive Streptococcus pneumoniae. These pathogens are prevalent causes of hospital-acquired pneumonia, and P. aeruginosa is particularly problematic with regards to chronic pulmonary infection in patients with Cystic Fibrosis (CF). Antibodies are known to provide a component of host-defence against this microbe, but recent evidence suggests that cells secreting the pro-inflammatory cytokine interleukin-17 (IL-17), namely T helper 17 (Th17) cells, are also significant in these responses. Aim: To investigate the sources of IL-17 and related cytokines during P. aeruginosa and S. pneumoniae infection, and to investigate if IL-1β has a role in Th17 formation during infection with these pathogens. Furthermore, to investigate the cytokine secretion of dendritic cells (DCs) derived from different sources following infection with these pathogens, and their roles at inducing Th17 secretion from naive CD4+ T cells. Methods & Results: Dendritic cells from mucosal sites were found to be better than GM-CSF derived bone marrow dendritic cells (BMDCs) at inducing Th17 cells from naive T cells. Th17 cells were derived in response to both P. aeruginosa and S. pneumoniae, with the role of IL-1β seeming to be negligible for P. aeruginosa. However, the role of IL-1β during Th17 cell induction during S. pneumoniae is unclear and needs further investigation. γδ T cells were found to be a source of IL-17 during P. aeruginosa infection in a IL-23 dependent manner. Furthermore, γδ T cells were also found to be a source of IL-22, yet the majority of cells were either IL-17 or IL-22 producing, not double producers as expected. In vivo infection with these pathogens identifed γδ T cells to be a main source of IL-17 during P. aeruginosa infection, with Th17 cells having more of a role during S. pneumoniae infection, yet the main sources of IL-17 still need to be identified. Preliminary infections with S. pneumoniae in IL-17RKO mice identified IL-17 as a key mediator in downstream inflammatory responses in the lung during infection. Conclusions: This study demonstrates that IL-17 responses are induced in response to infection with the respiratory pathogens P. aeruginosa and S. pneumoniae. Ex vivo, mucosal DCs were found to induce more robust Th17 cell responses compared to GM-CSF derived BMDCS. In vivo, Th17 cells appear to have a role in S. pneumoniae infection, with γδ T cells appearing to be the dominant source of IL-17 during P. aeruginosa infection. Furthermore, in vitro investigations of γδ T cells found them to be differentially IL-17 and IL-22 producing in response to P. aeruginosa infection, in a DC contact independent manner.

APA, Harvard, Vancouver, ISO, and other styles

19

Jaime-Ramirez, Alena Cristina. "HER2 and Folate Receptor Targeted Therapy is Enhanced by NK Cell-Activating Cytokines." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1364465780.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

McNally, Oonagh Rose. "Monokine secretion by tumouricidal macrophages." Thesis, University of Ulster, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359349.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Divangahi, Maziar. "Pseudomonas aeruginosa lung infection and respiratory muscle weakness : role of cytokines in diaphragm muscle dysfunction." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85903.

Full text

Abstract:

The primary muscle of respiration is the diaphragm. Diaphragm muscle dysfunction and ventilatory pump failure are well documented phenomena in animal models of sepsis. However, the primary cellular mechanisms underlying respiratory muscle dysfunction in sepsis are poorly understood. In addition, most investigations of respiratory muscle dysfunction in sepsis have been performed in models involving high doses of bacterial endotoxin and these investigations have been criticized on the basis of questionable relevance to human sepsis. Therefore, the objective in the first study of this thesis was to study respiratory muscle dysfunction in a more clinically relevant animal model, namely, the Pseudomonas aeruginosa pulmonary infection model. Remote inflammatory processes in different diseases, such as cancer, arthritis, sepsis, and cystic fibrosis are known to contribute to muscle wasting and weakness through more widespread systemic effects. In keeping with the above notion, we hypothesized that sustained P. aeruginosa lung infection would cause diaphragmatic and limb muscle weakness. In this thesis, we demonstrate for the first time that persistent pulmonary infection with P. aeruginosa induces significant dose- and time-dependent contractile dysfunction of the diaphragm. By comparison, prototypical slow- and fast-twitch hindlimb muscles were not influenced by pulmonary P. aeruginosa infection.
Because skeletal muscles can express a variety of immune modulating molecules such as cytokines, chemokines, adhesion molecules, and major histocompatibility molecules, the objective of the second study in this thesis was to study the possible role of pro-inflammatory cytokines in diaphragm muscle dysfunction in our animal model. Our results indicate for the first time that intra-diaphragmatic pro-inflammatory cytokine gene expression (TNF-alpha, IL-1alpha, IL-1beta, IL-6, and IL-18) is highly up-regulated in infected animals and the magnitude of such upregulation is dependent upon the dose of P. aeruginosa lung infection. Parallel to the absence of muscle contractile dysfunction in hindlimb muscle under the same conditions, P. aeruginosa infection did not alter the levels of pro-inflammatory gene expression within the hindlimb muscle. To further address the involvement of muscle-derived pro-inflammatory cytokines in diaphragmatic contractile dysfunction, we have employed recombinant adenovirus (Ad) as a vehicle for systemic delivery of the anti-inflammatory cytokine IL-10, in order to shift the balance between pro- and anti-inflammatory cytokines within the diaphragm toward a more anti-inflammatory profile. We report here that systemic delivery of Ad-IL-10 suppresses pro-inflammatory gene expression and improves force generating capacity of the diaphragm in P. aeruginosa infected animals. This finding emphasizes the role of anti-inflammatory cytokines as beneficial immune modulators in respiratory muscle failure caused by pro-inflammatory cytokines.
P. aeruginosa lung infection is a major cause of morbidity and mortality among cystic fibrosis (CF) patients and many patients with CF have weak peripheral and respiratory muscles. Although the role of pro-inflammatory cytokines has been extensively studied within the lungs of CF patients, the involvement of these cytokines in skeletal muscle dysfunction in animal models of CF or in human CF patients has not been studied. Therefore, in the third study of this thesis we have used mice sharing the same genetic defect as CF patients (Cftr knockout mice), in combination with our model of P. aeruginosa lung infection, to address several fundamental questions related to muscle function in CF. Our first objective in this portion of the thesis was to determine if diaphragmatic skeletal muscle cells express the CFTR mRNA. Our second objective was to ascertain whether intrinsic differences between CF and wild-type muscle cells could be detected in vitro, which might differentially affect the regulation of pro-inflammatory mediators in the setting of infection/inflammation. Our third objective was to evaluate possible differences in the ability of respiratory muscles to generate force prior to and after P. aeruginosa lung infection in Cftr knockout mice, as compared to their wild-type littermates. Finally, we aimed to determine if the absence of CFTR expression would predispose to muscle dysfunction triggered by up-regulation of intra-diaphragmatic pro-inflammatory gene expression. Our major results indicate that: First, in vitro stimulation with pro-inflammatory cytokines (TNF-alpha, IL-1alpha, and IFN-gamma) and LPS (extracted from Pseudomonas aeruginosa) triggered increased expression of pro-inflammatory mediators (iNOS, RANTES, MIP-1alpha, MIP-1beta, MIP-2 and KC) in both Cftr -/- and wild-type diaphragmatic myotubes, but the magnitude of cytokine/chemokine upregulation was significantly greater in CF than in wild-type diaphragm muscle cells. Sec
In the final study of this thesis, we sought to test the hypothesis that increased diaphragm muscle activation would lead to increased production of intra-diaphragmatic cytokine expression, since this could possibly explain the greater susceptibility of the diaphragm to express pro-inflammatory cytokines in response to pulmonary P. aeruginosa infection as compared with the hindlimb muscle. To test this hypothesis, we subjected rats to inspiratory resistive loading (IRL), corresponding to 45-50% of the maximum inspiratory pressure, and described that mRNA levels of IL-1beta, IL-6, and to a lesser extent, IL-4, IL-10, TNF-alpha, and IFN-gamma were all significantly increased in a time-dependent fashion in the diaphragm but not hindlimb muscle (gastrocnemius) of loaded animals. In addition, elevated protein levels of IL-1beta and IL-6 in response to loading were confirmed with immunoblotting and immunostaining. We also detected significant IL-6 protein to be localized inside diaphragmatic muscle fibers of loaded animals. We conclude that increased diaphragm muscle activity during resistive loading induces upregulation of pro-inflammatory cytokine gene expression in the diaphragm, which could also provide an explanation for the greater cytokine expression observed in the diaphragms of animals with P. aeruginosa lung infection.

APA, Harvard, Vancouver, ISO, and other styles

22

Hall, Deborah Jean. "Cytokines and their inhibition within the central nervous system in chronic relasping experimental allergic encephalomyelitis." Thesis, University of York, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238710.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Gabella, Kristin. "THE MECHANISMS BY WHICH REPEATED STRESS EXPOSURE ALTERS BRAIN CYTOKINES: IMPLICATIONS FOR DEPRESSIVE-LIKE BEHAVIOR." Kent State University Honors College / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1367676963.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Awang, Raja Azman Raja. "The role of IL-33 and IL-17 family cytokines in periodontal disease." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5515/.

Full text

Abstract:

IL-33 and IL-17 family cytokines (IL-17A – IL-17F) have been shown to play roles in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. However knowledge of their role in periodontal disease pathogenesis is limited. The aim of this study was therefore to determine clinical associations between IL-33 and IL-17 family cytokines and chronic periodontitis. In addition, to begin to investigate the biological significance of these associations using in vitro model systems. 97 patients with chronic periodontitis and 77 healthy volunteers were recruited in Glasgow and Newcastle. Serum, gingival crevicular fluid (GCF) and saliva were analysed for levels of IL-33 and IL-17 family cytokines by ELISA. Periodontal tissues from 17 chronic periodontitis patients and 10 healthy subjects from Glasgow were also investigated for IL-33 and IL-17 family cytokines mRNA expression by real time PCR. Immunohistochemical analysis was also performed on tissue to investigate expression of IL-33 and IL-17E at the protein level. In vitro experiments were performed using the OKF6/TERT-2 oral keratinocyte cell line and primary human gingival epithelial (PHGE) cells. The cells were stimulated with either a live Porphyromonas gingivalis monospecies biofilm or recombinant cytokines and changes in expression of cytokines, chemokines and their receptors evaluated by real-time PCR, immunocytochemical analysis or ELISA. In addition, transcriptional activity was monitored by analysis of changes in the phosphorylation (activation) of the NF-κB p65 subunit transcription factor using serum, GCF and saliva. IL-17A and IL-17A/F levels were higher in chronic periodontitis patients, but serum IL-17E was lower. IL-17A, IL-17A/F and the serum IL-17A:IL-17E ratio correlated positively with clinical parameters. IL-33, and IL-17 family cytokine (except IL-17B) gene transcripts were higher in tissue of chronic periodontitis patients. In addition, IL-33, ST2, IL-17E and IL-17RB proteins are expressed in periodontal tissues. Furthermore, IL-33 protein expression is upregulated in tissue of chronic periodontitis patients. In vitro models showed that IL-33 and its receptors (ST2 and ST2L) are expressed by oral keratinocytes (OKF6/TERT-2 cells and PHGE cells) and IL-33 expression up-regulated in response to P. gingivalis. However, IL-33 failed to induce expression of a range of inflammatory mediators and receptors in OKF6/TERT-2 cells. In vitro, IL-17E inhibited P. gingivalis monospecies biofilm and IL-17A induced expression of chemokines (IL-8 and/or CXCL5) by OKF6/TERT-2 cells at the transcriptional level by blocking the phosphorylation (activation) of the NF-κB p65 subunit. This study demonstrates clinical associations between IL-33 and IL-17 family cytokines and chronic periodontitis. The expression of IL-33 by oral keratinocytes and its up regulation upon exposure to P. gingivalis suggest it plays a role in the innate immune response to pathogens within the periodontium. However, the role of IL-33 in the periodontal inflammatory response remains to be elucidated. The negative correlations between serum levels of IL-17A and IL-17E and correlations with disease parameters, combined with their differing effects on the induction of expression of key neutrophil chemoattractants (CXCL5 and CXCL8), suggest opposing roles in periodontal immunity. Indeed, it can be hypothesised that the differential regulation of chemokine expression is due to IL-17A having pro- and IL-17E having anti-inflammatory properties. Indeed, as neutrophils play a key role in the early events associated with periodontal disease progression, the data suggests IL-17E is a rational target for therapeutic intervention.

APA, Harvard, Vancouver, ISO, and other styles

25

Delpoux, Arnaud. "Rôle de l’autoréactivité sur les capacités suppressives des lymphocytes T régulateurs CD4+ Foxp3+." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T052/document.

Full text

Abstract:

La plupart des lymphocytes T régulateurs CD4+ Foxp3+ (Tregs) sont générés dans le thymus. Plusieurs études suggèrent fortement que le développement des Tregs est dû à la forte affinité de leur TCR pour le soi (complexes « peptide du soi-CMH II ») présenté dans le thymus. Après avoir migré à la périphérie, les Tregs continuent d’interagir avec le soi et l’expression de Foxp3 est considérée comme nécessaire et suffisante pour maintenir le programme de transcription nécessaire aux fonctions suppressives de ces cellules en périphérie. En utilisant deux models expérimentaux chez la souris, notre étude démontre l’importance des interactions continues avec le soi pour maintenir les capacités suppressives des Tregs à la périphérie. L’absence d’interactions avec le soi aboutit rapidement à une altération du phénotype des Tregs, de leur capacité à produire certaines cytokines et modifie également leur signature transcriptionnelle. De façon intéressante, nous avons observé que l’absence d’interaction avec le soi n’affecte pas le niveau d’expression de Foxp3 mais que la reconnaissance du soi induit une signature transcriptionnelle unique et des caractéristiques fonctionnelles qui ne sont pas liées à Foxp3. Dans une seconde étude, nous avons mis en évidence que, chez la souris jeune adulte, l’expression de Ly-6C permet d’identifier deux sous-populations de Tregs distinctes présentant des différences phénotypiques et fonctionnelles. En particulier, nous avons observé que les Tregs Ly-6C- présentent un phénotype plus activé et régulateur que leurs homologues Ly-6C+ et que seules les premières sont fonctionnelles in vitro et in vivo. Nous avons également montré un lien étroit entre expression de Ly-6C et autoréactivité, les Tregs Ly-6C- recevant plus de signaux du TCR que les Tregs Ly-6C+. Finalement, nous avons observé que seuls les Tregs Ly-6C- se maintiennent à la périphérie avec le temps, suggérant l’existence d’une sélection périphérique permettant la survie préférentielle des Tregs les plus fonctionnels. Au cours de ma thèse, nous avons ainsi pu démontrer que les interactions avec le soi étaient indispensables et nécessaires pour la fonctionnalité, le phénotype et l’homéostasie des Tregs
Most regulatory T cells CD4 + Foxp3 + ( Tregs ) are generated in the thymus. Several studies strongly suggest that the development of Tregs is due to the high affinity of their TCR for itself (complex " self peptide - MHC II ') shown in the thymus . After migrating to the periphery, Tregs continue to interact with the self and the expression of Foxp3 is considered necessary and sufficient to maintain the transcriptional program required for suppressive function of these cells in the periphery. Using two experimental models in mice, our study demonstrates the importance of ongoing interactions with itself to keep the suppressive capacity of Tregs in the periphery. The lack of interaction with the so quickly leads to an altered phenotype of Tregs , their ability to produce cytokines and also changes their transcriptional signature. Interestingly , we observed that the lack of interaction with the so does not affect the expression level of Foxp3 but self-recognition induces a unique transcriptional signature and functional characteristics that are not related to Foxp3 . In a second study, we demonstrated that in young adult mice , the expression of Ly- 6C identifies two distinct subpopulations of Tregs with phenotypic and functional differences . In particular, we observed that Tregs Ly- 6C- have a more activated phenotype and control than their counterparts Ly- 6C + and only the former are functional in vitro and in vivo. We have also shown a strong link between expression of Ly- 6C and autoreactivity , Tregs Ly- 6C- receiving over TCR signals that Ly -6C + Tregs . Finally , we observed that only Tregs Ly- 6C- remain at the periphery over time , suggesting the existence of a selection device for the preferential survival of the most functional Tregs . During my thesis, we were able to demonstrate that interactions with the self were essential and necessary for the functionality, phenotype and homeostasis of Tregs

APA, Harvard, Vancouver, ISO, and other styles

26

Cooper, Megan Anne. "Cytokine Regulation of Natural Killer Cell Activation and Homeostasis." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1021398366.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Larsson, Anna-Karin. "Early life cytokines, viral infections and IgE-mediated allergic disease." Doctoral thesis, Stockholm : Wenner-Gren Institute for Experimental Biology, Stockholm university, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1224.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Minang, Jacob. "Cytokine responses in metal-induced allergic contact dermatitis : Relationship to in vivo responses and implication for in vitro diagnosis." Doctoral thesis, Stockholm : Dept. of Immunology, Wenner-Gren Institute, Stockholm University, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-717.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Herbert, Joan. "The regulation of specific antibody secretion by human B cells through contact and non-contact dependent mechanisms." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244614.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Becker, Juergen C. "Modulation of T-cell responses to murine melanoma by targeted-cytokine therapy." Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340737.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Mullins, Jeremi Stevan. "Immunomodulation of Human Skin Cells by Extracts of the Scabies Mite, Sarcoptes scabiei." Wright State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=wright1214591687.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Williams, Patrick. "The development and characterization of fusion cytokines of GMCSF with IL-21 and IFN-y for cancer immunotherapy." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96679.

Full text

Abstract:

Different immunotherapeutic strategies have been attempted against cancer, ranging from the use of cytokines like IL-2, to the use of dendritic cells, like Provenge, or the combinations of gene-modified, cytokine producing cellular vaccines, like GVAX. Immunotherapy has progressed slowly because either the induced immune response was not effective or because the heterogeneity of cancer can limit the effectiveness of inducing an immune response against a single antigen. Previous work in our lab has found that fusing GMCSF with γ-chain family cytokines produced novel immune modulatory effects and that cells treated with these fusion cytokines could be effective in treating diseases in mice. We generated a fusion of GMCSF and IL-21 (GIFT-21) with the aim of stimulating distinct, but complementary, elements of the innate and adaptive immune system. GIFT-21's aberrant interactions with its cognate receptors on macrophages induced an unanticipated pro-inflammatory response, resulting in B16 melanoma cancer rejection in C57Bl/6 mice and a significant survival advantage in NOD SCID mice. We further explored this phenomenon by treating mice with dendritic cells (DC) derived by treating monocytes with GIFT-21. B16 and D2F2/neu breast cancer growth was inhibited only in mice treated with antigen naïve GIFT-21 DCs. This effect was lost in CD8-/- and CCR2-/- mice and when mice were treated with β2 microglobulin deficient GIFT-21 DCs, and we confirmed that GIFT-21 DCs migrated to and sampled from the tumors to present tumor antigens to CCL2 recruited CD8+ T cells via MHCI.We also generated a separate fusion of GMCSF and IFN-γ (GIFY) with the aim of inducing a pro-inflammatory response by DCs and improving upon their antigen presenting properties. We confirmed that GIFY had superior cytostatic properties to IFN-γ and that it could induce DCs to present antigens to CD8+ T cells akin to the combination of GMCSF and IFN-γ. However GIFY was ineffective at preventing tumor growth when injected as a purified recombinant in mice bearing B16 melanoma tumors and when used as an adjuvant for DCs in the context of a tumor vaccine against EG-7 lymphoma.We conclude that GIFT-21 and its associated cellular products may serve as a novel therapeutic platform for the treatment of cancer and that GIFY may be appropriate in other settings.
Différentes stratégies immunothérapeutiques ont été considérées contre le cancer, allant de l'utilisation de cytokines comme l'IL-2, aux cellules dendritiques, tel que Provenge, ou à la combinaison de cellules modifiées génétiquement pour exprimer des cytokines produisant des vaccins cellulaires, tel que GVAX. Ces méthodes immunothérapeutiques ont progressé lentement puisque d'une part, la réponse immunitaire n'était pas efficace, et d'une autre part, l'hétérogénéité du cancer peut limiter l'efficacité à produire une réponse immunitaire contre un antigène particulier. Des recherches antérieures au sein de notre laboratoire ont révélé que la fusion de GMCSF avec la famille des cytokines de la chaîne gamma du récepteur de l'IL-2 ont produit des effets immunomodulateurs sans précédent. De plus, les cellules traitées avec ces cytokines fusionnées pourraient être efficaces dans le traitement de maladies chez les souris.Nous avons généré la fusion de GMCSF et IL-21 (GIFT-21) dans le but de stimuler des éléments distincts, mais complémentaires, du système immunitaire inné et adaptif. Les interactions aberrantes de GIFT-21 avec ses récepteurs des macrophages ont produit une réponse pro-inflammatoire inattendue, résultant en un rejet de la lignée cellulaire B16 des souris C57B1/6 et une survie significative des souris NOD SCID. Nous avons exploré davantage ce phénomène en injectant des souris avec des cellules dendritiques (DC) dérivées en traitant des monocytes avec GIFT-21. La croissance des cancers B16 et D2F2/neu a seulement été inhibée dans les souris injectées avec des cellules dendritiques traitées avec GIFT-21 sans pré-incubation avec un antigène. Par contre, cet effet n'a pas été observé dans les souris CD8-/- et CCR2-/-, ni lorsque nous avons injecté des souris avec des cellules dendritiques GIFT-21 déficientes en microglobuline β2. Nous avons confirmé que les cellules dendritiques GIFT-21 ont migré vers les tumeurs et les ont échantillonées afin de présenter des antigènes à travers MHCI à des cellules T CD8+ recrutées par CCL2. Nous avons également généré une fusion de GMCSF et IFN-γ (GIFY) dans le but d'induire une réponse pro-inflammatoire chez les cellules dendritiques et d'ainsi améliorer leur habileté a présenter des antigènes. Nous avons confirmé que GIFY possède des propriétés cytostatiques supérieures à IFN-γ et qu'il pourrait induire les cellules dendritiques à présenter des antigènes à travers des cellules T CD8+ similaires à la combinaison de GMCSF et IFN-γ. Par contre, GIFY s'est montré inefficace à prévenir la croissance des tumeurs lorsqu'injecté en tant que recombinante purifiée dans des souris avec des tumeurs B16 et lorsqu'utilisé en tant qu'adjuvant sous forme de vaccin pour des cellules dendritiques contre un lymphome EG-7. Nous pouvons conclure que GIFT-21 et ses produits cellulaires pourront servir de plate-forme thérapeutique sans précédent pour le traitement du cancer et que GIFY pourrait être approprié dans d'autres contextes.

APA, Harvard, Vancouver, ISO, and other styles

33

Creery, W. David. "Effects of immunoregulatory cytokines on B7-1 and B7-2 isoform expression on human monocytes and B cells." Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/10195.

Full text

Abstract:

T cell activation and the generation of effective immune responses is critically dependent on APC-derived signalling. The relative expression of B7 isoforms on APC may be important in determining the nature and extent of the immune response, and immunoregulatory cytokines may mediate their effects through alterations in B7 isoform expression. The effects of a panel of cytokines on B7 isoform expression on resting and activated monocytes and B cells was evaluated. IL10 and IL4, which induce the development of Th2 type T cells, downregulated expression of B7-2 and modestly upregulated expression of B7-1 on unstimulated human monocytes. IFN$\gamma,$ a potent inducer of Th1 type T cells, upregulated both B7-1 and B7-2 expression. TNF$\alpha$ downregulated B7-2 expression, but did not alter B7-1 expression. Addition of anti-IL10 antibodies did not abrogate the effects of TNF$\alpha$ on B7-2 expression. LPS had effects on B7 isoform expression on purified monocytes similar to those of IL10 in PBMC, namely marked B7-2 downregulation and modest B7-1 upregulation. None of the cytokines influenced the levels of expression of B7 isoforms on either resting or activated B cells. Thus cytokines that influence development of T helper type immune responses have differential effects on expression of individual B7 isoform on monocytes but not on B cells. These findings may have important implications in activation and control of immune responses in infections, autoimmunity and malignancies.

APA, Harvard, Vancouver, ISO, and other styles

34

Moëll, Annika. "Inflammatory Mediators and Enterovirus Infections in Human Islets of Langerhans." Doctoral thesis, Uppsala University, Department of Oncology, Radiology and Clinical Immunology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8501.

Full text

Abstract:

Type 1 diabetes (T1D) is due to a selective loss of the insulin producing β-cells. However, the process responsible for this loss is still unknown. There is accumulating evidence that enteroviruses (EVs) are involved in T1D. In addition to direct virus-induced cytolysis, EVs could facilitate β-cell destruction by inducing inflammatory cytokines. Induction of such genes has previously been shown in EV-infected islets in vitro. Modulation of inflammatory mediators expressed in the islets could be a possible strategy to reduce β-cell destruction.

In the first paper we screened uninfected isolated human islets for genes with the potential to induce or modulate an immune response. We found that several of the genes expressed in the islets encode proteins with a powerful biological activity, such as IL-1β, IL-8, MIP-2α, MCP-1 and MIF. This indicates that the islets themselves can express several triggers of inflammation, and if expressed in vivo these mediators would probably contribute to β-cell destruction.

The vitamin B3 derivate, nicotinamide (NA), has been shown to modulate expression of factors important for coagulation and inflammatory responses. Addition of NA into isolated islet cultures resulted in a reduced expression of the pro-inflammatory chemokine MCP-1 and the coagulation activator tissue factor, suggesting that NA may have implications for both inflammatory responses and the pro-coagulant activity of islets.

We successfully isolated EVs from three newly diagnosed T1D patients. All isolates showed tropism for human islets and β-cells in vitro and clearly affected islet function. We also found that EV infection induced islet secretion of the chemokines IP-10 and MCP-1and that this induction could be blocked or reduced by addition of NA to the culture medium. Interestingly, NA also reduced viral replication and virus-induced islet destruction.

To conclude, this thesis provides new information about expression and modulation of inflammatory mediators in infected and uninfected human islets that could trigger inflammatory reactions leading to β-cell destruction. Moreover, it further strengthens the causal relationship between EV and T1D.

APA, Harvard, Vancouver, ISO, and other styles

35

Johansson, Elin. "Effects of immunostimulatory DNA in the pig : induction of immunoregulatory cytokines by plasmid DNA, virus or bacteria /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 2002. http://epsilon.slu.se/avh/2002/91-576-5949-4.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Milora, Katelynn Ann. "Characterization of IL-1 and IL-36 Cytokines in Health and Disease." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/451599.

Full text

Abstract:

Microbiology and Immunology
Ph.D.
Epithelial cells are the first line of defense against invading pathogens and external threats in the environment. Keratinocytes, often not perceived of as immune cells, release cytokines in response to infection or injury to signal danger to neighboring cells and recruit effector leukocytes to prevent further damage to the host. IL-1 and IL-36 cytokines are a group of closely related proteins that share similarities in structure and function and have been shown to play key roles in inflammatory responses of epithelial tissues. While IL-1, consisting of IL-1α and IL-1β, have been widely studied and recognized as pinnacle cytokines in a variety of inflammatory responses, relatively little is understood about IL-36 cytokines since their discovery more than 15 years ago, and how they differ from their better-known IL-1 relatives. IL-36 cytokines, consisting of IL-36α, IL-36β, and IL-36γ, signal through the same receptor, IL-36R, which is expressed most abundantly on epithelial cells. IL-36 proteins garnered attention when it was discovered that a missense mutation in the gene encoding the naturally occurring receptor antagonist, IL-36Ra, was associated with the deadly form of psoriasis, generalized pustular psoriasis (GPP). This disease is characterized by episodic flares of keratinocyte hyperproliferation leading to red scaly lesions all over the body, excessive neutrophil recruitment to the epidermis resulting in pustule formation, and severe fever. Our data presented here demonstrate that IL-36α, but not IL-36β or IL-36γ is critical for the psoriatic phenotype, including epidermal thickening and neutrophil recruitment, generated during a murine model of psoriasis induced by the drug Imiquimod. Furthermore, IL-36α was found to induce IL-1α expression and vice versa through a signaling feedback loop which perpetuated disease. These data provide insight into mechanisms whereby IL-36 signaling can lead to excessive inflammatory effects in patients with pre-existing regulation deficiencies, which can lead to acute flares of disease. Beyond their association with disease, IL-1 has been shown to contribute to anti-bacterial and anti-viral responses of the immune system by upregulating inflammatory signals and chemoattractants. Herpes Simplex Virus-1 (HSV-1) is a human pathogen that has developed several strategies to manipulate elements of the immune system to avoid detection by the host. One such mechanism is the prevention of activation and release of IL-1β from infected cells thereby blocking its pro-inflammatory responses. Our data show that keratinocytes infected with HSV-1 actively release IL-1α to alert danger to neighboring cells to circumvent this blockage of IL-1β signaling. This release of IL-1α initiates recruitment of leukocytes to early HSV-1 microinfection sites resulting in increased protection against disease, as evident by the increased mortality rate of mice deficient in the IL-1 receptor, IL-1R1. This study, for the first time in vivo, demonstrates the ability of IL-1α to act as an alarmin to initiate an immune response to combat infection. The role of IL-36 cytokines during viral infections has been less defined than that of IL-1. Several studies have shown the upregulation of IL-36 expression during viral infections in epithelial tissues, such as HSV-1 and Influenza, yet a direct link has not been established between these proteins and anti-viral responses. Our research presented within this thesis show that IL-36β, but not IL-36α nor IL-36γ, provides protection against the lethal outcome of cutaneous HSV-1 infection, as demonstrated by IL-36β knockout mice dying earlier and more often than wild type mice. Surprisingly, while previous reports have found IL-36 cytokines to be capable of activating the adaptive immune system, our results found no significant differences in development of HSV-1 specific antibodies or CD8+ T cell development between wild type and IL-36β knockout mice. Furthermore, we found no significant differences in viral copy numbers at infection sites between the two groups. Although our data show that IL-36β clearly plays a critical role in controlling the outcome of HSV-1 infection, further studies are necessary to define the mechanisms behind this protection. The final section of this thesis focuses on the endogenous nature of IL-36 cytokines, specifically IL-36γ, and their potential processing. IL-36 cytokines were originally believed to be synthesized as full-length fully active proteins; however, large concentrations of the recombinant proteins were required to elicit cellular responses in vitro. Since then, studies have shown that IL-36 cytokines gained up to 1000-fold increases in reactivity following processing at very specific N-terminal locations of each individual cytokine, however this processing has never been shown to occur in vivo. These studies were recently expanded when neutrophil proteases were found to be responsible for processing of these proteins in vitro. Data presented here show, for the first time, that IL-36γ may be endogenously processed by neutrophils in wounded murine skin in vivo, yet, the amino acid processing site appears to be different from that predicted. Although further studies are required to fully characterize the nature of this processing, these data provide valuable insight into the natural mechanisms involved in the potential activation of these cytokines. Taken together, the research presented within this thesis sheds light on the mechanisms whereby IL-1 and IL-36 cytokines enhance immunological defenses against potential threats, and yet, can contribute to disease if unregulated. Furthermore, these studies demonstrate the evolutionary advantage of producing multiple cytokines that appear to have redundant roles within the body, yet can provide multiple levels of protection to the host. This knowledge contributes to our overall understanding of these proteins and their contribution to immunological systems within the body.
Temple University--Theses

APA, Harvard, Vancouver, ISO, and other styles

37

Robbin, Melissa Gina. "The role of trophoblast cells in regulating immunological tolerance." Thesis, Royal Veterinary College (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572479.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

O'Toole, Alison. "Tumour Necrosis Factor-#alpha# signalling : potential roles in the pathophysiology of multiple organ failure." Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364934.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Daftarian, Mohammad Pirouz. "Studies on the roles of T helper type I and type II cytokines in HIV immunopathogenesis, role and regulation of interleukin-10." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21962.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Kryworuchko, Marko Andrii. "Regulation of CD44 and its adhesive interactions with the extracellular matrix component, hyaluronan, by cytokines in normal and transformed human B lymphocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0015/NQ46528.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Chan, Wan-yi, and 陳韻怡. "Influenza A virus replication and cytokine responses in murine macrophages in vitro." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B33829937.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Kantola, T. (Tiina). "Systemic inflammation in colorectal cancer:the role of cytokines and endostatin." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526210544.

Full text

Abstract:

Abstract Colorectal cancer (CRC) is among the most common cancers in Finland. Prognostic factors are important for predicting disease outcome and adjusting optimal treatment. The currently used prognostic methods for CRC have their limitations and consequently several biomarkers have been studied to find potential prognostic markers, but none have been adapted for routine use so far. In the present study, the relationships between the components of the immune system and other factors modulating tumor growth were assessed and their suitability to be used for use as prognostic tools in CRC were studied. The study material consisted of blood samples and surgical specimens collected from 148 CRC patients operated on in Oulu University Hospital and blood samples of 86 healthy controls. Concentrations of endostatin and 27 cytokines were measured from preoperative serum samples and control samples. Immunohistochemical methods were used for collagen XVIII and inflammatory cell analyses. The levels of several cytokines were altered in CRC patients compared to the controls. The serum cytokine profile achieved an excellent accuracy in discriminating CRC patients from healthy controls. Advanced CRCs were associated with elevated cytokine levels and a metastasized disease was linked to an orientation towards Th2 cytokine milieu. The presence of systemic inflammation, depicted by a modified Glasgow Prognostic Score (mGPS), correlated to CRC progression. The serum endostatin levels were elevated in CRC and correlated with invasion through muscular layer and systemic inflammation, but not with densities of local inflammatory cells. Collagen XVIII was expressed in tumor stroma and in the muscle layer of bowel wall. The serum cytokines and tumor infiltrating immune cells showed relatively weak associations. In conclusion, CRC is associated with significant alterations in serum cytokine milieu, which underlines the relevance of studying several cytokines and their relative alterations. The serum cytokine profile is a promising tool for discriminating CRC patients from healthy controls, but its clinical value needs to be validated. The elevated endostatin levels may result from invasion-related cleavage of collagen XVIII in the bowel wall, but further studies are needed to determine the value of endostatin in CRC prognosis
Tiivistelmä Paksu- ja peräsuolisyöpä (kolorektaalisyöpä) on yleisimpiä syöpämuotoja Suomessa. Sen ennustetta kuvaavat mittarit ovat tärkeitä taudin etenemisen ennustamisessa ja hoidon suunnittelussa. Käytössä olevat kolorektaalisyövän ennusteen arvioinnin menetelmät eivät ole riittäviä. Uusia merkkiaineita onkin kehitetty ja testattu, mutta rutiinikäyttöön soveltuvia menetelmiä ei ole vielä löydetty. Tässä tutkimuksessa selvitettiin immuunijärjestelmän ja muiden kasvaimen kasvua säätelevien tekijöiden keskinäisiä yhteyksiä ja niiden merkitystä kolorektaalisyövän ennusteen arvioinnissa. Tutkimusmateriaali koostui Oulun yliopistollisessa sairaalassa leikattujen kolorektaalisyöpäpotilaiden (n = 148) leikkaus- ja verinäytteistä ja terveiden verrokkihenkilöiden (n = 86) verinäytteistä. Endostatiinin ja 27 sytokiinin pitoisuudet mitattiin seeruminäytteistä. Kollageeni XVIII:n ja tulehdussolujen analysoimiseen käytettiin immunohistokemiallisia menetelmiä. Useiden sytokiinien pitoisuudet olivat korkeammat potilailla kuin verrokeilla, mutta osassa sytokiineista pitoisuudet olivat alentuneet. Seerumin sytokiiniprofiili erotteli luotettavasti potilaat verrokeista. Pidemmälle edenneeseen tautiin liittyi sytokiinien korkeampia pitoisuuksia ja etäpesäkkeitä muodostanut tauti oli yhteydessä Th1-tyypin sytokiinien esiintymiseen. Systeeminen tulehdusreaktio oli yhteydessä syövän etenemiseen. Endostatiinipitoisuudet olivat kohonneet potilailla ja olivat yhteydessä kasvaimen invaasioon suolen seinämän lihaskerroksen läpi. Endostatiinipitoisuudet korreloivat myös systeemisen tulehdusreaktion kanssa, mutta eivät liittyneet paikallisten tulehdussolujen määrään. Kollageeni XVIII ilmentyi kasvaimen stroomassa ja suolen seinämän lihaskerroksessa. Sytokiineilla ja kasvaimen paikallisilla tulehdussoluilla todettiin olevan vain vähän keskinäisiä yhteyksiä. Kolorektaalisyöpään liittyy useita erisuuntaisia muutoksia seerumin sytokiinipitoisuuksissa, joten on olennaista tutkia eri sytokiinien suhteellisia muutoksia. Seerumin sytokiiniprofiili on lupaava potilaita ja verrokeita erotteleva mittari, jolla voi olla diagnostista arvoa. Kohonneet endostatiinipitoisuudet potilailla voivat johtua kasvaimen invaasioon liittyvästä kollageeni XVIII:n hajoamisesta suolen seinämässä, mutta lisätutkimuksia tarvitaan endostatiinin ennustetta kuvaavan arvon määrittämiseksi

APA, Harvard, Vancouver, ISO, and other styles

43

Boka, Kylene. "The Effects of Temperature and Humidity on the Inflammatory Response during Aerobic Exercise." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1541762506473021.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Baigrie, Robert John. "Cytokine and other components of the integrated host response to injury." Thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/26464.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Namjoshi, Prachi Mukund. "Th-1 Cytokine and Antibody Mediated Immunity against HER Family Expressing Breast Cancer Cells." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1461250751.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Starbeck-Miller, Gabriel. "The regulation of CD8 T cell responses by inflammatory cytokines and FcγRIIB." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4762.

Full text

Abstract:

Antigen-specific CD8 T cells provide an important protective role in response to infection by viruses, intracellular bacteria, and parasites. Pathogen-specific CD8 T cells render this protection by undergoing robust expansion in numbers while gaining the ability to produce cytokines and cytolytic machinery. Following expansion and effector differentiation, pathogen-specific CD8 T cells will contract in number while further differentiating into a highly functional population of memory CD8 T cells. These antigen-experienced cells persist in secondary lymphoid organs and the periphery in order to rapidly respond to repeated infection. Creating optimal CD8 T cell responses to infection can be critical for raising sufficient armament to provide protection against invading intracellular pathogens. Although CD8 T cells have protective value, many vaccine strategies tend to focus on creating productive B cell antibody responses to promote immunological protection. Even though antibody responses can be highly protective, coupling optimal CD8 T cell responses with B cell responses could provide higher orders of protection than either one on their own. Therefore, a deeper understanding of the pathways that ultimately guide the magnitude of CD8 T cell responses is required to achieve this potential therapeutic benefit. My studies evaluate the role of receptor signaling events in guiding the expansion of activated CD8 T cells during primary and secondary responses. Specifically, the first portion of my studies dissect the mechanism by which direct IL-12 and Type I IFN stimulation can substantially bolster primary CD8 T cell responses in vivo. Within this context, I demonstrate that direct IL-12 and Type I IFN signaling increases CD8 T cell accumulation during primary expansion by prolonging division without altering survival. IL-12/Type I IFN signaling promoted prolonged division of activated CD8 T cells by maintaining high-affinity IL-2 receptor subunit (CD25) expression and IL-2 signaling. The other portion of my work was dedicated to understanding the expression and role of the inhibitory FcgR (FcgRIIB) during primary and secondary CD8 T cell responses. FcgRIIB expression could be detected as early as the peak of the CD8 T cell response and marked activated CD8 T cells that were highly sensitive to antigen stimulation. Although FcgRIIB did not appear to play a substantial role in regulating the magnitude of primary CD8 T cell responses, it played an important role in inhibiting the expansion and cytotoxicity of memory CD8 T cells during homologous challenge. Collectively, these data highlight potential avenues that could be exploited by future therapies that aim to achieve appropriately sized CD8 T cell responses.

APA, Harvard, Vancouver, ISO, and other styles

47

Madan, Rajat. "Novel insights into the in vivo biology of Interleukin-10." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1242133534.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

MERLOT, Élodie. "Modulation de la production de cytokines par l'environnement." Phd thesis, Institut national agronomique paris-grignon - INA P-G, 2003. http://tel.archives-ouvertes.fr/tel-00007518.

Full text

Abstract:

Les conséquences immunitaires d'un stress d'origine environnementale sont complexes et encore difficilement prévisibles. Le stress affecte le système immunitaire soit en agissant sur l'immunité innée, en altérant la réactivité inflammatoire, soit en agissant sur l'immunité acquise, en modulant la production de cytokines dites Th1 et Th2. L'environnement social
contribue largement au développement et à l'expression de maladies. Dans les espèces sociales, la position sociale occupée dans le groupe module la susceptibilité aux infections mais les supports endocriniens et immunitaires de ces différences de susceptibilité sont ignorés. La remise en cause de l'organisation sociale engendre un stress important dont les conséquences immunitaires sont encore sujettes à controverse.
Ce travail de thèse a pour objectifs (1) de décrire l'influence du statut social sur le fonctionnement des systèmes endocrinien et immunitaire, (2) de préciser les effets du stress
social sur la production de cytokines et la susceptibilité aux infections et (3) de rechercher des facteurs à l'origine de la variabilité des conséquences immunitaires du stress social.
Chez le porcelet, un regroupement après le sevrage élève transitoirement le cortisol salivaire et altère le comportement mais n'affecte pas la réactivité des lymphocytes sanguins.
La suite des travaux a utilisé une procédure de défaite sociale chronique chez la souris. Les résultats obtenus mettent en évidence une influence du statut social. En absence de stress, les
dominants présentent des niveaux de base de corticostérone et une réponse spécifique à la tuberculine supérieurs aux dominés. Suite à une défaite sociale, les dominants sont plus affectés que les dominés. La défaite sociale augmente la réactivité inflammatoire mais ne modifie pas de façon nette l'équilibre de la production de cytokines de type Th1 et Th2 et n'affecte pas l'immunité spécifique développée contre une infection mycobactérienne. Les conséquences immunitaires de la défaite sociale ne sont observées que lorsque le stress est associé à des combats et à des blessures. Ces travaux montrent que la réponse au stress dépend de l'histoire sociale de l'individu, en particulier de son statut social. De plus, les
répercussions immunitaires du stress dépendent aussi de l'histoire immunitaire récente. En effet, une réaction inflammatoire systémique inhibe la libération plasmatique de cytokines
inflammatoires en réponse à un stress psychologique ultérieur.

APA, Harvard, Vancouver, ISO, and other styles

49

Lucas, Elizabeth A. "TLR4 Stimulation Induces SLAMF9-Mediated Regulation of Cytokine Production and Ras Signaling." Miami University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=miami1590144828229019.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Bobrie, Angélique. "Rôle des protéines Rab27 dans la sécrétion des exosomes : implication dans l’étude des réponses immunitaires tumorales." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T082/document.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Immunology; Cytokines'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles