Tesi sul tema "Immunomodulation"
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1
Hoopen, Petra ten. "Immunomodulation of jasmonate functions". [S.l. : s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=969394403.
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2
DeClue, Amy E. "Ketamine immunomodulation during endotoxemia". Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/6276.
Testo completoAbstract (sommario):
Thesis (M.S.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "August 2007" Includes bibliographical references.
3
Kaplan, Jennifer Melissa. "Immunomodulation During Systemic Inflammation". University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1186158205.
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4
Sanders, Robert A. "GABAA immunomodulation & infection". Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9981.
Testo completoAbstract (sommario):
GABAergic drugs, such as benzodiazepines, are widely used in clinical practice yet their immune side effects are poorly understood. Preliminary studies have suggested that immune cells express GABAA receptors indicating that they may be controlled by GABA signaling. Herein parallel preclinical, translational and epidemiological approaches are described to help understand the importance of GABAA immunomodulation. The hypothesis is that GABA signaling acts to reduce responsiveness to a pathogen and thus that GABAergic drugs will increase susceptibility to infection. To inform on the clinical importance of this work, data from a subgroup analysis of the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial (where the relative effects of lorazepam, and dexmedetomidine were compared) are described in septic and non‐septic patients. Consistent with the hypothesis, avoidance of lorazepam sedation decreased mortality by 70% in septic patients but did not affect outcome in non‐septic patients. As preclinical data suggests that benzodiazepines increase mortality at subsedative doses we next conducted a population‐based cohort and nested case‐control design analysis of The Health Improvement Network (THIN), a comprehensive UK general practice database. Benzodiazepines exposure increased the incidence of community acquired pneumonia (CAP) and both 30‐day and long‐term mortality from CAP. Based on these significant accumulating data of the harm of exposure to benzodiazepines during an infection, animal studies were conducted to understand (i) the biological plausibility of our findings and (ii) the mechanism of the effect. In a series of mouse studies the prototypical benzodiazepine, diazepam, increased mortality from Streptococcus pneumoniae through potentiation of GABAA signaling. The increased mortality was associated with increased pathogen load and a delayed cytokine response to the infection. However cellular recruitment was not affected, indicating that local mechanisms were perturbed. Immune cell profiling revealed that alveolar macrophage and monocytes abundantly expressed subunits of the GABAA receptor, compatible with benzodiazepine sensitivity. Ex vivo studies showed that GABAA receptor activation decreased cytokine responses, phagocytosis and bacterial killing by alveolar macrophage likely via inducing an intracellular acidosis. Finally based on the immune cell profile of GABAA receptors we predicted that benzodiazepines that do not target the α1 GABAA subunit would lack the immune suppression observed by nonselective drugs. In accordance with this hypothesis we show that these selective benzodiazepines do not provoke intracellular acidosis, affect cytokine release or bacterial killing of macrophage ex vivo. In vivo the selective benzodiazepine did not increase mortality from infection or increase pathogen load.
5
Demols, Anne. "Immunomodulation de la pancreatite experimentale". Doctoral thesis, Universite Libre de Bruxelles, 2003. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211321.
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6
Islander, Ulrika. "Immunomodulation by estrogen and estren /". Göteborg : Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at Göteborg University, 2007. http://hdl.handle.net/2077/3123.
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Mattsson, Lars. "Immunomodulation of collagen-induced arthritis /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4369-9/.
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8
Barber, K. A. "Immunomodulation in the NOD mouse". Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596341.
Testo completoAbstract (sommario):
A CD8+ T cell clone was generated by priming non-diabetic NOD mice with C2, a Kd-binding, 10-mer peptide (WYIPQSLRGV) derived from the large isoform of GAD. This clone (αC2.4) lyses NOD fibroblast targets transfected with a construct encoding human GAD67. This molecule is entirely homologous with mouse and rate GAD67 at the C2 region and as such this observation indicates that C2 is a naturally processed epitope. The object of this project was to investigate the role of the C2 epitope and altered peptide ligand (APL) derivatives in IDDM pathogenesis in the NOD mouse, with the ultimate aim of modifying disease by induction of antigen specific tolerance. Adoptive transfers into neonatal NOD and NOD-scid recipients have shown αC2.4 not to cause disease. Neither do these cells home to the pancreas. Surface marker characterization demonstrated that αC2.4 did not express β7 integrin, a horning receptor thought to play a key role in infiltration of the pancreas by autoreactive cells. However, administration of the C2 peptide was shown to reduce the incidence of spontaneous but not cyclophospamide induced disease, although this effect was dependent on the route of administration. Knowledge of the specificity of the CD8+T cell clone allowed investigation of the nature of T cell recognition of peptide/MHC as a basis for the search for an APL. Three residues of positions 5, 7 and 8 of the C2 peptide were shown to be critical for recognition of peptide/MHC by αC2.4. On the basis of these findings variant peptides were synthesized and screened by antagonistic properties. None was identified with the ability to alter recognition of C2/MHC by αC2.4. Cytokine intervention has been shown to be an important approach for immune modulation in IDDM in the NOD mouse. The aim of this aspect of the project was to use recombinant retroviral vector technology to modify islet specific T cell clones for targeted expression of immunosuppressive cytokines. Transduction of T cells was achieved although the efficiency of this process was limited. This approach may prove useful in altering the local cytokine milieu towards a non-pathogenic Th2 environment.
9
Dua, Harminder Singh. "Immunomodulation of experimental autoimmune uveitis". Thesis, University of Aberdeen, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317710.
Testo completoAbstract (sommario):
Chronic posterior uveitis is a relatively common clinical disorder and an importance cause of visual impairment in young adults. Experimental autoimmune uveitis (EAU) and its associated experimental autoimmune pinealitis (EAP) induced by retinal autoantigens are predominantly CD4+ T cell mediated (auto) immune disease of the retina and uveal tract of the eye and the pineal gland respectively. EAU bears a close clinical and pathological resemblance to chronic posterior uveitis in humans and seves as a good animal model for the study of posterior uveitis. The EAU model was used to study means of modulating the host's immune response to suppress or inhibit the onset of uveitis. The onset of retinal S-antigen induced EAU could be successfully inhibited by pre-treating Lewis rats with a retinal S-antigen (carboxy terminus) specific monoclonal antibody called S2.4.C5. This however did not suppress the associated EAP indicating that the monoclonal antibody acted via the efferent arc of the immune mediated response. This prompted a study of the 'Blood-retinal and Blood-pineal barrier sites' during the active stages of EAU and EAP. Transmission electron microscopy of the vascular endothelium revealed changes resembling 'High endothelial venules' of lymph nodes in the retinal and pineal vasculature. In an attempt to identify one or more immunodominant epitopes of S-antigen that may be relevant to tolerance induction, an in-vitro and in-vivo study using enzyme digested preparations of S-antigen was carried out. This revealed that digestion of S-antigen by a protease derived from staphylococcus aureus V8 strain, not only inhibited the binding of the monoclonal S2.4.C5 in-vitro but was also associated with an in-vivo attenuation of the pathogenic response to S-antigen indicating that a dominant immunogenic epitope of S-antigen was located at the C-terminus of the molecule.
10
Merly, Liza. "Immunomodulation by Shark Cartilage Extracts". FIU Digital Commons, 2011. http://digitalcommons.fiu.edu/etd/420.
Testo completoAbstract (sommario):
The immune system is composed of innate and adaptive mechanisms. Innate immune responses are significantly modulated by immunomodulatory factors that act through the induction of specific patterns of cytokine production in responding cells. Human leukocytes have been shown to respond to substance(s) present in acid extracts of commercial shark cartilage (SC). Shark cartilage is a food supplement taken by consumers as a prophylaxis and for the treatment of conditions ranging from arthritis to cancer. No reliable scientific evidence in the literature supports the alleged usefulness of shark cartilage supplements, but their use remains popular. Cartilage extracts exhibit immunomodulatory properties by inducing various inflammatory, Th1-type cytokines and potent chemokines in human peripheral blood leukocytes (HPBL) in vitro. The objectives of the study were to (1) to determine the nature of the active component(s), (2) to define the scope of cellular response to SC extract, and (3) to elucidate the molecular mechanisms underlying bioactivity. Results showed that there are at least two cytokine-inducing components which are acid stable. One anionic component has been identified as a small (14-21 kDa) glycoprotein with at least 40% carbohydrate content. Shark cartilage stimulated HPBL to produce cytokines resembling an inflammatory, Th1 polarized response. Leukocyte-specific responses consist of both initial cytokine responses to SC directly (i.e., TNF-a) and secondary responses such as the IFN-γ response by lymphocytes following initial SC stimulation. Response of RAW cells, a murine macrophage cell line, indicated that TNF-α could be induced in macrophages of another mammalian species in the absence of other cell types. The results suggest that the human monocyte/macrophage is most likely to be the initial responding cell to SC stimulation. Stimulation of cells appears to engage at least one ligand-receptor interaction with TLR 4, although the role of TLR 2 cannot be ruled out. Initial activation is likely followed by the activation of the JNK and p38 MAPK signal transduction pathways resulting in activation, release, and translocation of transcription factor nuclear factor κB (Nf-kB). This dissertation research study represents the first in-depth study into characterizing the bioactive component(s) of commercial shark cartilage responsible for its immunomodulating properties and defining cellular responses at the molecular level.
11
Norris, Carol Rose. "Immunomodulation in experimental feline asthma /". For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.
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12
Saurer, Timothy Benjamin Lysle Donald T. "Neuroimmune mechanisms of opioid-mediated immunomodulation". Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1436.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Psychology Behavioral Neuroscience." Discipline: Psychology; Department/School: Psychology.
13
Milioti, Natalia. "Immunomodulation of atherosclerosis using dendritic cells". Thesis, University of Surrey, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608344.
Testo completoAbstract (sommario):
Inflammation plays a crucial role in atherosclerotic plaque generation/progression. Dendritic cells (DCs). cellular immune-response components linking innate and adaptive immune systems, have been found in atherosclerotic plaques. In this study, Des were examined as a possible therapeutic tool to modulate the inflammatory immune response underlying plaque formation. Apolipoprotein (apo) B-100 derived antigens are believed to modulate humoral immune responses to achieve atheroprotection, but their role in cellular immunity remains unclear. Therefore, one objective was to characterise the immunomodulatory effect of apoB-100-derived peptides (P2, P45, P210) on immature DCs (iDCs) and naive T lymphocytes ill vitro. iDCs were generated from bone-marrow progenitor-cells of male apoE-'- mice. Peptide up-take and processing was studied by confocal microscopy after 6h, 2411 and 48h. Peptide P45 was found in the endolysosomal compartments, co-localising with MHC-I and :MHC-II antigen-presenting complexes. The phenotypic and differentiation characteristics of P2, P45 and P21O-Joaded DCs were studied by flow cytometry, and cytokine and matrix metalloproleinase production by PCR/ELISA after 48h. Proliferation and differentiation of T lymphocytes driven by peptide-loaded DCs was also studied. Peptide-loaded DCs displayed a tolerogenie phenotype similar to that of unloaded, iDCs, and inhibited CD4+ proliferation induced by mature DCs when co-cultured. My results suggest that the protective effect of the peptides could be mediated by DCs presenting them to T cells. A second objective was to examine the effect of vaccination with tolerogenic DCs (toIDCs), generated in vitro through incubation with IL-10 and TGF-β for 6 days, on atherosclerotic progression in apoE-/- mice. This showed that immunisation with tolDCs increased the number of CD8+CD25'FoxP3+ T regulatory cells as well as secretion of IL-l0 within the spleen of immunised mice. IL- l0 levels were also elevated in the serum, while cholesterol levels were reduced, although plaque size remained unchanged. These results provide new insights for treatment and prevention of atherosclerosis through vaccination.
14
Price, Claire. "Immunomodulation by Advanced Glycation End-Products". Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508487.
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Mellor, C. M. "Immunomodulation and chemotherapy of parasitic infections". Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378990.
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16
Sadler, Clare Helen. "Immunomodulation during chronic murine Schistosomiasis mansoni". Thesis, University of York, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369342.
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Saraiva, Margarida Sofia da Silva Santos. "Immunomodulation by poxviruses : TNF receptor homologues". Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619688.
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18
Jones, Joanne Louise. "Long-lived immunomodulation following Campath-1H". Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612015.
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Mussai, Francis Jay. "Immunotherapy and immunomodulation for haematological malignancies". Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:6120e659-0dab-4447-b4d6-75e235d3b2c8.
Testo completoAbstract (sommario):
HA22 is an immunotoxin composed of an anti-CD22 variable fragment linked to a 38 kDa truncated protein derived from Pseudomonas exotoxin A. The mechanisms of cytotoxicity and resistance of HA22 against Acute Lymphoblastic Leukaemia (ALL) and Burkitt’s lymphoma were studied. Using a bone marrow mesenchymal cell culture assay to support ALL cell viability, I? investigated the in vitro cytotoxicity of HA22 against ALL blasts from newly diagnosed and relapsed patients. There was interpatient variability in sensitivity to HA22. There was no significant difference in HA22 sensitivity between diagnosis and relapse samples but peripheral blood ALL blasts were more sensitive to HA22 than those from bone marrow. The mechanisms of resistance to HA22 were studied, using cell lines as a model. The number of CD22 sites/ cell and the rates of immunotoxin internalisation did not affect HA22 cytotoxicity. HA22 mutants with resistance to lysosomal degradation and enhanced targeting to the endoplasmic reticulum had improved cytotoxicity. The role of apoptosis pathways proteins in HA22-mediated cell death was studied. Their role is complex but raised levels of the anti-apoptotic pathway protein Bcl-2 were found in the most resistant NALM6 cell line. Penetration of HA22 into Burkitt’s lymphoma masses was studied using a flow cytometric based method. HA22 rapidly penetrated into the lymphoma masses, however a barrier to further uptake is present which could not be overcome by the addition of adriamycin or taxol in the murine xenograft model. The ability of Acute Myeloid Leukaemia (AML) blasts to create an immunosuppressive niche was investigated using a cell line model and primary patient samples. AML blasts suppress T cell proliferation through altered arginine metabolism, dependent on the enzymes arginase II and iNOS. Small molecule inhibitors to arginase and iNOS restored T cell proliferation in vitro. AML further enhances its immunosuppressive niche by transforming surrounding monocytes into an M2-immunosuppressive phenotype, in an arginase dependent manner. The immunomodulatory protein Serum Amyloid A (SAA) was secreted by AML blasts, and leads to AML chemotaxis, IL-1production, and release of S100A9 protein. Finally, invariant Natural Killer T cells (iNKT) were shown to be cytotoxic to some AML blasts, in the presence of Galactosylceramide, and thus able to restore T cell proliferation. The results provide a strong rationale for the clinical testing of these novel immunotherapeutic and immunomodulatory strategies in patients with haematological malignancies.
20
Moreno, Navarrete José María. "Immunomodulation and metabolism: possible role of lactoferrin". Doctoral thesis, Universitat de Girona, 2011. http://hdl.handle.net/10803/36737.
Testo completoAbstract (sommario):
To gain insight in the relationship between innate immune system and metabolic disease, we aimed to investigate the effects of lactoferrin in obesity-related metabolic disturbances.
Circulating lactoferrin concentration was significantly decreased in subjects with altered glucose tolerance (AGT) and associated negatively with obesity-related metabolic disturbances. The SNPs-induced aminoacidic changes in lactoferrin N-terminus region were associated with a low atherogenic lipid profile. Lactoferrin production in neutrophils decreased significatively in aging, chronic low-grade inflammation and type 2 diabetes. In vitro, lactoferrin increased insulin signaling pathway, even under insulin resistance conditions and displayed dual effects on adipogenesis (antiadipogenic in 3T3-L1 and adipogenic in human adipocytes). In conclusion, lactoferrin might play a potential protective role against insulin resistance and obesity related metabolic disturbances.Per aprofundir en la relació entre el sistema immunològic innat i els trastorns metabólics, s’investiga l’efecte de la lactoferrina en els desordres metabòlics associats a l’obesitat. Els nivells circulants de lactoferrina es trobaven significativament disminuits en subjetes amb la tolerància a la glucosa alterada (AGT), i aquests es correlacionaven negativament amb trastorns metabòlics associats a obesitat i resistència a la insulina. Els canvis aminoacídics en la seva regió N-Terminal s’associaven a un perfil lipídic menys aterogènic. La producció de lactoferrina es troba reduïda en condicions d’envelliment, inflamació crònica i diabetes tipus 2. In vitro, la lactoferrina incrementava la via de senyalització de la insulina, inclús en condicions de resistència a la insulina i presentava efectes dual en la adipogenesis (antiadipogenic en 3T3-L1 i adipogenic en adipòcits humans). En conclusió, la lactoferrina podria tenir un potencial efecte protector enfront les enfermetats metabòliques associades a obesitat i resistència a la insulina.
21
Vallance, Bruce A. "The immunomodulation of intestinal smooth muscle function". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0023/NQ51017.pdf.
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Hjerpe, Charlotta. "Immunomodulation and its effector mechanisms in atherosclerosis /". Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-177-7/.
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23
Zhang, Gaofeng. "Electric signals regulated immunomodulation and wound healing". Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/42430/.
Testo completoAbstract (sommario):
Endogenous electric fields (EFs) are present during a variety of physiologic and pathologic events, including penetrating injury to epithelial barriers. An applied electric field with strength within the physiologic range can induce directional cell migration of epithelial cells, endothelial cells, fibroblasts, and immune cells suggesting a potential role in controlling cell behaviours during wound healing. Dendritic cells (DCs) and dermal fibroblasts were used to explore the molecular mechanisms underlie EF-induced cell activities during two aspects of wound healing: immune response and remodelling. In this study, we investigated the effects of applied EFs on several types of DCs in response to IL18. DC progenitor cells KG-1 shows dose dependently response to EFs stimulation to increase IFN-γ expression. Moreover, the migration of KG-1-derived DCs and Langerhans cells (LCs) in mouse skin showed increased response to IL18 with directional migration when exposed to EFs in vitro and ex vivo. Furthermore, the in vivo investigation suggested that pharmacologically increased trans-epithelial potential difference (TEPD) induced LCs to emigrate from skin to draining lymph node. The sensitization of DCs to IL18 can be strengthened by EFs through redistribution of IL18 receptors and phosphorylation of p38 MAPK. We also comparatively studied the responses of human chronic wound fibroblast (CWF) and chronic matched fibroblast (CMF) to applied EFs with addition of platelet derived growth factor (PDGF). The results indicate that 1) EFs induce human dermal fibroblast directional migration in a voltage dependent manner. 2) CWF shows impaired sensitivity in response to EFs compared to CMF and HF. 3) Activation of PDGFR and PI3K are both required for EF-induced directional migration. 4) PDGF attenuates EF-induced migration directedness through PDGFR-ROCK other than PI3K pathway. 5) Optimised concentration of PDGF plus physiological EFs enhance chronic wound healing. We propose that the EF-induced re-distribution of the receptors on the cell surface results in a shift of membrane receptors between the cathode-facing and the anode-facing membrane of the cell. There would be a higher probability to overcome the threshold of signal transduction at the higher density receptor side. The downstream IV signalling cascade therefore can be ignited. Understanding the signalling pathways underlying guidance cues (EFs, cytokines, chemokines) will help to optimise future therapies for immunomodulation, vaccination, wound healing and regeneration.
24
Williams, Richard David. "Immunomodulation of reproductive function in domestic ruminants". Thesis, University of Nottingham, 2004. http://eprints.nottingham.ac.uk/28687/.
Testo completoAbstract (sommario):
Active immunisation against GnRH inhibits reproductive function by inducing a hypogonadotropic condition associated with gonadal atrophy. Despite economic, ethical and environmental advantages of GnRH immunisation in cattle over conventional castration methods, the technology has not yet been commercially adopted. Primarily because of the requirement for numerous booster vaccinations because of the reversibility of physiological effects, the commercial efficacy of immunocastration is currently poor. However, neonatal GnRH immunisation in sheep can result in a permanent suppression of reproduction (Brown et al., 1994; 1995; Clarke et al., 1998). These findings and a study in pigs (Molenaar et al., 1993) indicate that, the hypothalamic/pituitary gland unit (HPU) may be particularly susceptible to GnRH antibodies during a specific window of development in the pre-pubertal animal, but no long-term studies in cattle have been conducted. Therefore the primary objective of this project was to determine the effect of neonatal immunisation against GnRH in cattle. Beef cross bull (n=9; Chapter 3) and heifer calves (n=9; Chapter 4) were vaccinated against a newly developed (Pfizer®) GnRH construct vaccine at -2, 6 and 13 weeks of age. Nine calves of each sex served as negative controls, receiving saline injections only. The GnRH vaccine had proved effective (Dr. A.R. Peters, personnel communication 2000) in inducing immune responses and reducing variation between animals in unpublished industrial studies, compared to earlier vaccines, and hence was reasoned to be capable of raising GnRH antibodies despite the relative immaturity of the neonatal immune system. Following vaccination, circulating GnRH antibodies and reproductive hormones, such as FSH (Chapters 3 and 4), testosterone (Chapter 3), progesterone (to assess onset of puberty) and oestradiol (Chapter 4) were measured and additional intensive serial bleeds were carried out to assess LH parameters up to and beyond puberty (puberty defined by testes circumference in bulls). Gonadal (antral follicles and testes growth) and accessory gland development was quantified throughout the trial using ultrasound scanning. Sexual behaviour (Chapter 3) was studied from 38 weeks of age, while an assessment of sperm quality (Chapter 3), and anabolic response to vaccination was also performed post-mortem (Chapters 3 and 4). GnRH immunisation in neonatal calves did not permanently impair reproduction. A temporary suppression in reproductive function was evident through the disruption of pituitary gland function, as indicated by a reduction of LH pulse amplitude and mean plasma LH concentrations (Chapters 3 and 4). In addition, a reduction in medium- sized follicle numbers, testes growth, plasma testosterone concentration, vesicular gland length and juvenile aggression occurred. Some beneficial anabolic effects were observed e.g., carcass composition grades. Changes all occurred subsequent to increased GnRH antibody titres in immunised cattle. Despite some evidence of prolonged effects on LH amplitude and circulating testosterone after anti-GnRH titres had dissipated, all inhibited parameters, except carcass quality, returned to levels comparable to control animals by 72 weeks of age. No treatment effects on FSH concentrations, large follicle numbers, reproductive tracts (post mortem) or peri- and post-pubertal behaviours were observed following treatment. Sperm morphological abnormalities tended to be more prevalent in GnRH immunised bulls. A significant increase in GnRH antibody titres occurred at -23 weeks of age (Chapter 4), this may have been a rebound in antibody titre, possibly caused by an anti-idiotype immune response (antibody response to GnRH antibodies), or due to significant maturational changes in immune function at this time causing a delayed response to vaccination. Alternatively a novel "auto-immune" response may have been detected, which if confirmed/repeatable might be incorporated into an immunisation protocol to act as a "self-booster". However, no previous reports of such an event have been published and further investigation is urgently required. A more prolonged or permanent suppression of reproductive function may be possible following an earlier, greater and more sustained elevation of antibody titres during the neonatal period. Further development of GnRH vaccines and/or protocols (prime-boost, cytokine modulation vaccines, concomitant passive and active immunisation and pregnant cow GnRH vaccination), and studies of performance and GnRH antibody mechanism(s) of action in cattle are required. Chapters 3 and 4 provide a comprehensive study on pubertal development and neonatal GnRH vaccination, thus contributing significantly to knowledge in these fields. Currently, the vaccine used in this trial may be used to delay puberty in older calves or transiently suppress reproductive function to aid management. The economical viability of animal production systems such as beef and lamb are closely related to rates of reproduction. The Fec B gene in ewes increases ovulation rate and litter size, possibly through the development of precocious follicles, which can switch their primary dependence from FSH to LH. As a result, more follicles are selected to continue growth to an ovulatory size. The precise mechanisms by which these processes occur have recently been shown to involve oocyte follicle interactions (see section 1.1.5). Follicle development is modulated by GHIIGF and inhibin, however attempts to increase follicular development and ovulation through active inhibin immunisation alone have been variable and hence not commercially attractive. To develop successful protocols to induce twin ovulations in cows· and ewes, without superovulation, a clearer, more details understanding of follicullogenesis is required. The objective of the current study was to better understand these mechanisms through investigating interactions of GH/GF and inhibin in the ovary, follicle development, steroidogenesis, and receptor populations using an anoestrous sheep model. Spring born Mule x Charolais ewe lambs were actively immunised (n=8) against porcine inhibin α-C 1-26 peptide conjugated to KLH in NUFCA (primary and 3 boosters (NUFA», while 8 served as negative controls. Seven days following the final booster, the ewes were subdivided to give four groups: (1) controls + saline (n=4); (2) controls + rbGH (4ml s.c; 1mg. mr1; n=4); (3) inhibin immunised + saline (n=4); and (4) immunised + rbGH (n=4). Recombinant bovine growth hormone (rbGH) was given (Lm.) for 6 days. On day 4 GnRH (Receptal®; 1 ml) was injected s.c, to all animals to initiate the beginning of a new follicular wave. Blood samples were collected fortnightly to measure inhibin antibody titres, IGF-I, FSH and steroids. On the seventh day ensuing slaughter serum antibodies and ovaries were harvested. Left ovaries were intended for ISH (mRNA for P450arom) and/or immunohistochemical analysis. Follicles from right ovaries were dissected out, counted, measured and cultured in M199 at 37°C for 2 hours. Culture media was then assayed for oestradiol. Follicle shells were stored at -180°C for LH receptor binding studies. This work reports on the influence of different treatments on follicle populations. All immunised animals produced antibodies, which bound to 1251-inhibin. Using ANOVA to compare treatments it was observed that, Inhibin immunisation significantly (P
25
Rigg, Keith Malcolm. "Immunomodulation of circulating lymphocytes in colorectal cancer". Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241446.
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Pollock, Emma. "Gluten antigenicity and immunomodulation in coeliac disease". Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407704.
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Jordan, Robert William. "Humoral immunomodulation induced by toxigenic Pasteurella multocida". Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419136.
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Chimen, Myriam. "Immunomodulation by adipokines in type 1 diabetes". Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3581/.
Testo completoAbstract (sommario):
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which the immune system specifically targets and destroys the pancreatic insulin-producing beta-cells. We are interested in defining whether adipose tissue-derived cytokines (adipokines) such as adiponectin (anti-inflammatory) and leptin (pro-inflammatory) could influence T1D progression. We demonstrate the expression of the leptin receptor (LEPR) on peripheral blood mononuclear cells (PBMC) and observed higher expression of LEPR on PBMC from patients with T1D. However, we found no significant functional relevance for this observation. On the other hand, we show lower expression of the adiponectin receptors on lymphocytes from patients with T1D. This was associated with a reduced capacity of adiponectin to inhibit lymphocyte trans-endothelial migration in T1D. We show that adiponectin strongly inhibited lymphocyte migration by action on the endothelium or directly on the lymphocytes. We have now established that adiponectin action is not directly targetting the lumphocytes but involves accessory cells that express higher level of the adiponectin receptors. These findings were validated \(in\) \(vivo\) using a peritonal model of inflammation and led to the discovery a newly idnetified agent able to control the transmigration of T cells. These observations underline the importance of adiponectin in the control of lymphocyte transmigration during an inflammatory response and offer a potential therapeutic agent for T cell mediated diseases.
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Yuan, Kai. "Metabolic inflammation and immunomodulation in dairy cows". Diss., Kansas State University, 2014. http://hdl.handle.net/2097/17294.
Testo completoAbstract (sommario):
Doctor of PhilosophyDepartment of Animal Sciences and Industry
Barry J. Bradford
The transition period in dairy cows is characterized by dramatic increases in nutrient requirements for lactation and substantial metabolic stress. The disturbed metabolic balance, coupled with suppressed immune function, contributes to markedly elevated incidence of health disorders. Several lines of evidence suggest that increased inflammation is common during the transition period. Unlike the classical inflammation associated with acute infection, the postpartum inflammatory state is low-grade and often of metabolic origin. This metabolic inflammation plays a key role in numerous disorders; an improved understanding of inflammatory pathways in transition cows may improve our ability to predict and prevent disorders. To mimic metabolic inflammation, in Experiment 1, we administered low amounts of recombinant bovine tumor necrosis factor-α (rbTNFα), a pro-inflammatory cytokine, to early lactation cows, and evaluated whether rbTNFα affects milk production, metabolism, and health. We found that rbTNFα administration increased systemic inflammation, decreased feed intake and milk yield, and increased incidence of disorders. Conversely, preventing excessive inflammation has the potential to improve productivity and health of dairy cows. To identify nutritional strategies that could enhance metabolism and immunity, we evaluated the efficacy of several feed additives. In Experiment 2, we evaluated effects of chromium propionate, rumen-protected lysine and methionine, or both on metabolism and immunity in lactating dairy cows, and found that supplementation of these nutrients may enhance neutrophil function. In Experiment 3, we determined whether supplementation of yeast product to transition cows could enhance production, metabolism, and immunity, and found that yeast product modulated feeding behavior, metabolism, immunity, and uterine inflammation. Overall, a greater understanding of the role of metabolic inflammation in the transition period and the nutritional strategies that could modulate these signals may improve the production and health of dairy cows.
30
Harizi, Hedi. "Cellules dendritiques et éicosanoi͏̈des : production et immunomodulation". Bordeaux 2, 2002. http://www.theses.fr/2002BOR28957.
Testo completoAbstract (sommario):
Les cellules dendritiques (CD) jouent un rôle central dans le développement et la régulation de l'immunité. Elles sont rares et difficiles à isoler, c'est pourquoi nous avons optimisé la production de ces cellules in vitro à partir des précurseurs myéloides en présence du GM-CSF et d'IL-4. La génération et les propriétés phénotypiques et fonctionnelles de ces cellules sont étroitement liées aux conditions de culture, aux facteurs utilisés et au microenvironnement cellulaire. Dans ce travail, nous montrons que la génération des CD à partir de la moelle osseuse ainsi que leur activité immunomodulatrice peuvent être modulées par les eicosanoides. Les CD possèdent toute la machinerie enzymatique requise à la biosynthèse des PGs et des LTs et n'ont pas besoin de substrat exogène pour produire suffisamment de PGE2 et LTB4 quantifiable par ELISA et par chromatographie à phase gazeuse. En terme d'immunomodulation, les eicosanoides affectent l'expression des molécules de co-stimulation, la capacité des CD à activer les lymphocytes T ainsi que la production d'IL-10 et d'IL-12. L'activation des CD par du LPS induit une forte expression de la protéine COX-2 responsable d'une importante production de PGE2. Ce médiateur lipidique inhibe considérablement la production d'IL-12 par les CD via un mécanisme dépendant de l'IL-10. Ceci permet de comprendre pourquoi ces cellules sont capables d'induire le phénomène de tolérance. L'interaction entre les eicosanoides peut moduler le métabolisme de l'AA et aboutir à une production régulée des eicosanoides. Nous montrons que la PGE-2 inhibe la voie 5-LO responsable de la biosynthèse de LTB4. Cette inhibition médiée par l'IL-10, porte essentiellement sur l'expression de la protéine membranaire qui fixe et présente l'AA à la 5-LO, appelée FLAP. Enfin, la PGE2 module les fonctions des cellules dendritiques via un mécanisme faisant intervenir essentiellement les récepteurs EP2 et EP4.
31
Steck, Ryan Perry. "Pharmacologic Immunomodulation of Macrophage Activation by Caffeine". BYU ScholarsArchive, 2014. https://scholarsarchive.byu.edu/etd/4251.
Testo completoAbstract (sommario):
Caffeine is one of the most widely used neurostimulants in the world and there is considerable debate on its effect in immune cells. One of its main targets is proposed to be adenosine receptors which mediate an anti-inflammatory switch in activated immune cells while another target is phosphodiesterase where it acts as an inhibitor. In macrophages, caffeine has been shown to cause both pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. If the primary effect of caffeine on macrophages were to antagonize adenosine receptors we would expect cells exposed to caffeine to have a prolonged M1 response. However, we show that caffeine suppresses phagocytosis at physiological concentrations (an indicator of M2 phenotype). This suppression was reversed when macrophages were pretreated with protein kinase A inhibitor, suggesting that at physiological concentrations caffeine's phagocytic suppression may be due to its function as a phosphodiesterase inhibitor, pushing cells towards an M2 fate. However, mRNA expression profiling suggests that caffeine can modulate A2A receptor expression and suppress MKP-1 expression, a hallmark of M1 macrophages. Caffeine is, therefore an immunomodulator that can suppress or prolong inflammatory responses in macrophages, which may account for the abundance of contradicting evidence in the literature. Additionally, these effects are complicated by regular caffeine intake and fitness level, emphasizing that tolerance and immune robustness are important factors in macrophage activation.
32
Mockridge, James William. "Immunomodulation of GH activity : application and potential mechanisms". Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627200.
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Copland, A. "The immunomodulation of dendritic cells by Neisseria meningitidis". Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1472931/.
Testo completoAbstract (sommario):
Neisseria meningitidis is a pervasive bacterial coloniser of the human nasopharynx with up to 40% carriage in the population. Paradoxically, invasive disease occurs in only ~1 in 100,000 individuals. Sophisticated immune evasion mechanisms allow the bacterium to persist in the host, yet these adaptations may also enable its transition from a harmless commensal to an invasive pathogen. Dendritic cells (DC) are principal controllers of mucosal immunity, and bacteria can exploit their maturation process to evade the immune system. In this study, it is reported for the first time that live serogroup B meningococcus (NmB) impedes DC maturation by disrupting STAT1 through dephosphorylation of tyrosine 701 (Y701). DC were therefore refractory to interferon stimulation—which is essential for DC function—and had low levels of maturation markers and other STAT1 dependent genes. Interestingly, infected DC retained the activity of other major signalling pathways, including the MAP kinases, which induced PD L1hi DC that were CD4+ T-cell suppressive. Disruption of STAT1 also had the major effect of dampening SOCS1 and CISH expression, which are critical for homeostatic control of DC inflammatory cytokine production, and correlated with enhanced inflammatory cytokine production. Restoration of STAT1-Y701 phosphorylation reprogrammed DC towards a typical CD86hi maturation state, normalised cytokine profiles and T-cell responses. These data establish an unconventional inflammatory pathway for the meningococcus, but also link immune evasion and pathogenesis via a shared mechanism. These findings elucidate how NmB may undermine immunity within the normal mucosa but also inflict damage in the context of septicaemia due to uncontrolled inflammation.
34
Murray, Patrick Francis. "Immunomodulation within the head and neck tumour microenvironment". Thesis, University of Hull, 2014. http://hydra.hull.ac.uk/resources/hull:10124.
Testo completoAbstract (sommario):
Changes in the immune response have been implicated in the progression of squamous cell carcinoma of the head and neck (HNSCC). Evidence is emerging that processes within the tumour microenvironment can lead to immune modulation and subsequent tumour growth or metastasis. The hypothesis of this thesis is that the HNSCC tumour microenvironment will have increased levels of cytokines that produce an overall negative effect on the cellular cytotoxic immune response against the malignant cells. Specifically, it is hypothesised that a Th-2-like anti-inflammatory response will favour tumour cell progression and be associated with advanced stage HNSCC. This thesis examines the levels of a panel of immune cytokines to investigate whether difference in these levels have an association with the progression of the disease and other standard clinico-pathological factors. A method of protein extraction from tumour tissue and detection of quantitative cytokine levels was developed and optimised. A cohort of 69 patients newly-presenting with HNSCC was recruited prospectively to the study, with a total of 83 samples of primary HNSCC tumour tissue and metastatic nodal tissue being investigated. Increased levels of TGF-β, described as concentration of cytokine/mg total protein extracted, (median 1051 pg/mg vs. 659 pg/mg, p= 0.004) and reduced levels of IL-17 (median 4.2pg/mg vs. median 18.6 pg/mg, p= 0.009), compared with normal tissue from control patients were reported. The HNSCC samples were also found to have higher levels of VEGF in tumour samples (83 pg/mg vs. 27.6 pg/mg, p=0.026) compared with control tissue. No difference was found in the levels of IL-2, IL-10, IL-12, IL-15, or IL-17. When comparing early stage (I-III) to late stage IV HNSCC patients it was found that there were significantly lower levels of the Th1-like IL-12 in the higher stage IV patients (median 50pg/mg vs. 21 pg/mg, p= 0.01), and significantly higher levels of IL-15 in stage IV patients (median 52 pg/mg, vs. 20 pg/mg p= 0.03). In summary, analysis of cytokine levels within the tumour microenvironment of HNSCC may be of prognostic value, and further study of the immune suppressive nature of HNSCC could open potential therapeutic approaches, especially if such data are correlated with other cellular parameters, e.g. T regulatory or CD8+ve T cell levels.
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Gautherot, Isabelle. "Anti-messagers et ribozymes : médiateurs d'une immunomodulation spécifique". Lyon 1, 2003. http://www.theses.fr/2003LYO10001.
Testo completoAbstract (sommario):
L'efficacité d'un vaccin de même que l'issue d'un processus pathologique sont déterminées par l'équilibre TH1/TH2 de l'immunité. La polarisation d'une réponse immune est principalement gouvernée par le profil d'expression des cytokines, médiateurs de l'immunité. Aussi la régulation différentielle de leur synthèse pourrait-elle permettre de diriger une réponse, vers le phénotype TH le plus adapté. Antisens, ribozymes et DNAzymes ont été évalués en tant que modulateurs séquence-spécifiques de l'expression de cytokines respectivement pro-TH1 ou pro-TH2 : l'IL-12 et l'IL-4. Différents modèles de sélection - in vitro, cellulaires et pseudo-cellulaires - ont été développés et évalués en parallèle dans le cadre de cette étude. La régulation de l'IL-4 a constitué l'essentiel de ce travail. Le variant d'épissage antagoniste IL-4[delta]2 fait de cette cytokine-clé TH2 une cible particulièrement intéressante. L'existence de ce variant, vraisemblablement limitée aux primates et à quelques mammifères supérieurs, nous a conduit à proposer un regard nouveau sur le choix de modèles d'expérimentation animale. Des anti-messagers et ribozymes actifs ont été isolés. La possibilité de réguler de manière différentielle les deux variants IL-4 a pu être plus particulièrement démontrée en contexte cellulaire. Les propriétés immunomodulatrices in vivo des candidats régulateurs isolés devront être évaluées dans un modèle de stimulation antigénique. Les différents systèmes de sélection développés pourraient s'inscrire, de par leur complémentarité, dans une stratégie d'évaluation raisonnée, appropriée à la sélection d'immunomodulateurs oligonucléotidiques à visée thérapeutique. Le concept de régulation différentielle d'expression permet d'envisager une multitude d'applications, aussi bien prophylactiques que thérapeutiques. Le ciblage sélectif de variants à l'aide d'anti-messagers, potentiellement adaptable à d'autres médiateurs de l'immunité, pourrait marquer la naissance d'une ère de l'immunomodulation spécifique et dirigée.
36
Santos, Michael Carmelo Orda. "Immunomodulation of Flavonoid Biosynthesis in Transgenic Arabidopsis thaliana". Diss., Virginia Tech, 2001. http://hdl.handle.net/10919/27349.
Testo completoAbstract (sommario):
In an effort to test the feasibility of intracellular expression of enzyme-targeted antibodies to alter metabolism, recombinant antibody fragments in the single-chain format (scFv) were isolated from a phage display library using Arabidopsis chalcone isomerase (CHI) of the flavonoid biosynthetic pathway as the antigen. Each of the genes encoding the scFvâ s was cloned into a plant transformation vector, which was subsequently used to generate transgenic plants. One transgenic line with low expression of one of the scFvâ s appeared to have an altered flavonoid metabolism, as evidenced by a reduced capacity for anthocyanin accumulation and a reduction in flavonol glycosides in seedlings. Strong corroborating evidence that implicated the binding of scFv to CHI in the phenotypic alterations was obtained from protein mobility shift assays. Taken together, the results indicate that scFv-mediated metabolic alteration is possible in plants. Thus, we show that intracellular expression of scFvâ s can be exploited as an additional tool for metabolic engineering.Ph. D.
37
Manickam, Cordelia. "IMMUNOPATHOGENESIS AND IMMUNOMODULATION INDUCED BY PRRSV STRAIN VR2332". The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366361539.
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38
Hietter, Hélène. "Activites biologiques des hydroxysterols : cytotoxicite selective et immunomodulation". Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13323.
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Ferreira, Daniela Filipa Alves. "Influence of substrates composition on immunomodulation by MSCs". Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16048.
Testo completoAbstract (sommario):
Mestrado em Biomedicina MolecularMesenchymal stem cells (MSCs) are non-hematopoietic multipotent stem cells capable to self-renew and differentiate along different cell lineages. MSCs can be found in adult tissues and extra embryonic tissues like the umbilical cord matrix/Wharton’s Jelly (WJ). The latter constitute a good source of MSCs, being more naïve and having a higher proliferative potential than MSCs from adult tissues like the bone marrow, turning them more appealing for clinical use. It is clear that MSCs modulate both innate and adaptive immune responses and its immunodulatory effects are wide, extending to T cells and dendritic cells, being therapeutically useful for treatment of immune system disorders. Mechanotransduction is by definition the mechanism by which cells transform mechanical signals translating that information into biochemical and morphological changes. Here, we hypothesize that by culturing WJ-MSCs on distinct substrates with different stiffness and biochemical composition, may influence the immunomodulatory capacity of the cells. Here, we showed that WJ-MSCs cultured on distinct PDMS substrates presented different secretory profiles from cells cultured on regular tissue culture polystyrene plates (TCP), showing higher secretion of several cytokines analysed. Moreover, it was also shown that WJ-MSCs cultured on PDMS substrates seems to possess higher immunomodulatory capabilities and to differentially regulate the functional compartments of T cells when compared to MSCs maintained on TCP. Taken together, our results suggest that elements of mechanotransduction seem to be influencing the immunomodulatory ability of MSCs, as well as their secretory profile. Thus, future strategies will be further explored to better understand these observation and to envisage new in vitro culture conditions for MSCs aiming at distinct therapeutic approaches, namely for immune-mediated disorders.
As células estaminais mesenquimais (MSCs) são células não-hematopoéticas, multipotentes, capazes de se auto-renovar e de diferenciar em diferentes tipos celulares. As MSCs estão presentes em tecidos mesenquimais e de tecidos extra embrionários, tais como a matriz do cordão umbilical/Wharton’s Jelly(WJ). Estes últimos constituem uma boa fonte de de MSCs, sendo estas mais naive e tendo um maior potencial de proliferação do que as MSCs obtidas de tecidos adultos, como a medula óssea, tornando as MSCs da matriz do cordão umbilical/Wharton’s Jelly sejam mais apelativas para uso clínico. As MSCs possuem a capacidade de modularem tanto o sistema imune inato como o adquirido e os seus efeitos são vastos, afectando todas as células do sistema imune. Esta capacidade é bastante vantajosa para o uso terapêutico destas células em doenças do sistema imunitário. A mecanotransducção é por definição o mecanismos pelo qual as células convertem estímulos mecânicos em uma resposta bioquímica e com mudanças na sua morfologia. Apartir destas observações colocámos a hipotese de que mantendo MSCs in vitro em diferentes substratos poderia influencia a sua capacidade imunomoduladora. Com este trabalho, demonstrámos que ao plaquear MSCs em diferentes substratos de PDMS, estas mostram uma tendência para secretar quantidades diferentes de vários factores soluveis analisados, relativamente a MSCs mantidas em cultura em plataformas convencionais (placas de cultura de células - TCP). Para além disto, foi também observado que MSCs plaqueadas em substratos de PDMS aparentavam possuir uma maior capacidade imunomoduladora quando comparadas com MSCs mantidas em condições convencionais. Em conjunto todos os resultados obtidos sugerem que elementos relacionados com a mecanotransdução parecem influenciar a capacidade imunomoduladora de MSCs e a sua secreção de factores solúveis. Deste modo, estudos futuros poderão elucidar os mecanismos responsáveis por estas observações, de modo a permitir que se possa constitutuir melhores estratégias de cultura de MSCs para futuro uso terapêutico dirigido a doenças do sistema imunitário.
40
Harper, Fiona Helen. "The induction and immunomodulation of experimental autoimmune uveoretinitis". Thesis, University of Aberdeen, 1993. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU554654.
Testo completoAbstract (sommario):
Experimental Autoimmune Uveoretinitis (EAU), is a T cell mediated disease used as a model for several human inflammatory conditions affecting the posterior segment of the eye, which are immune mediated or autoimmune in nature. In this study an improved method of Interphotoreceptor Retinol Binding Protein (IRBP) preparation was devised (liquid chromatography), in order to establish the poorly characterised Lewis rat model of IRBP induced EAU. The progress of ocular inflammation induced by IRBP was investigated, both histologically (resin embedded, H &'38 E stained) and immunohistologically with particular reference to cells of the mononuclear phagocyte system. CD4&'43 lymphocytes out numbered CD8&43 lymphocytes in early focal lesions of the uvea and sites of retinal perivascular and ciliary body infiltration. A dominance reversed during disease resolution. Macrophages were also prominent throughout EAU: ED2 tissue macrophages in early retinal lesions; a prolonged presence of CD11b/CD18 mononuclear cells in the choroid and retina and early 'mass migration' into the photoreceptor region; and ED3 inflammatory macrophages in the vitreous and photoreceptor region during the late phase of disease. Once characterised this model of EAU was manipulated in vivo by the immunosuppressant macrolides Cyclosporin A, FK-506 and Rapamycin. In order to elucidate the key initiatory mechanisms responsible for the disease state the effects of immunosuppression on antibody production and in vitro cellular responses to antigen/mitogen were investigated.
41
Hietter, Hélène. "Activités biologiques des hydroxystérols cytotoxicité sélective et immunomodulation". Grenoble 2 : ANRT, 1986. http://catalogue.bnf.fr/ark:/12148/cb37598306w.
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42
McBee, Megan Earley. "Immunomodulation by subclinical persistent infection with Helicobacter hepaticus". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39916.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.Includes bibliographical references (leaves 112-118).
Recognition of polymicrobial infections is becoming important for understanding differential host responses to environmental exposures, vaccines, as well as therapeutics. Citrobacter rodentium is a well-characterized model of infectious colitis with particular usefulness for modeling human diarrheal disease or inflammatory bowel disease. Infection with Helicobacter hepaticus is subclinical and persistent in C57BL/6 mice, but causes disease in susceptible strains and immunodeficient mice. To test the hypothesis that subclinical persistent infection modulates the host response to diarrheal disease a polymicrobial mouse model utilizing H. hepaticus and C. rodentium was developed and characterized. Concurrent infection has been shown to modulate disease outcome through several mechanisms including: cross-reactivity between viral antigens; shifting T cell response from Th1 to Th2 by helminth infection; and induction of regulatory T cells that suppress host response. In this new model of polymicrobial infection, a new paradigm in which persistent infection prolonged the course of acute colitis associated with a deviation from Thl-biased disease to Th17 was observed.
(cont.) In addition, Foxp3+naturally-occurring regulatory T cells (nTre,) were markedly increased during active colitis. The accumulation of nTreg was sustained when mice were persistently infected with H. hepaticus, indicating on-going active colitis. Although persistent infection was able to modulate host response, protective immunity to a subsequent C. rodentium infection was not compromised. Persistent infection also modulated host response to soluble antigen by preventing induction of oral tolerance to single bolus, but not to continuous, high-dose antigen feeding. Using H. hepaticus infection of C57BL/6 mice, models to investigate the immunomodulatory potential of persistent infection on immunogenic responses of protective immunity to enteric infection, host response to polymicrobial enteric infection, as well as tolerogenic responses to soluble antigen were developed. These models establish baselines for further investigation into the influences of persistent infection on host immune responses.
by Megan Earley McBee.
Ph.D.
43
Belaz, Sorya. "Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action". Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B044/document.
Testo completoAbstract (sommario):
La leishmaniose est une maladie tropicale négligée pour laquelle l’arsenal thérapeutique actuel est limité. Ce travail de thèse s’est intéressé à rechercher des nouvelles cibles thérapeutiques en ciblant la paroi des leishmanies. Le lipophosphoglycane (LPG), constituant majoritaire de la paroi, présente un motif glucidique particulier, le galactofuranose, qui semble une cible thérapeutique intéressante car il est absent des membranes de mammifères. Les galactofuranosyl-transférases sont impliquées dans le métabolisme de ce furanose, et ce travail a débuté par l’étude de ces enzymes et par la caractérisation d’une mutase, également nécessaire au métabolisme du galactofuranose. Une fois les cibles caractérisées dans les 2 stades du parasite, des analogues du galactofuranose ont été testés quant à leur capacité antiparasitaire sur les formes promastigotes et amastigotes de Leishmania donovani. Un composé s’est révélé intéressant et a été plus étudié, le n-octyl-galactofuranose (Galf). Différentes approches ont été utilisées pour caractériser son mode d’action sur les promastigotes et les amastigotes : résonance paramagnétique électronique, microscopie électronique à transmission, cytométrie en flux ou résonance magnétique nucléaire. L’observation d’une activité inductrice du métabolisme oxydatif des macrophages nous a conduits à nous intéresser aux capacités immunomodulatrices de ces analogues galacto-furanosidiques. Ainsi la dernière partie de ce travail est consacrée à l’étude de la polarisation des macrophages par les galactofuranosides, sur un modèle in vitro de macrophages humains. Nous avons pu montrer que le Galf exerçait une activation des macrophages en faveur d’une polarisation de type M1, ce qui pourrait expliquer l’effet limitateur de croissance des amastigotesLeishmaniasis is a neglected tropical disease for which the current therapeutic arsenal is limited. This work aimed at finding new therapeutic drugs by targeting the Leishmania cell wall. Lipophosphoglycan (LPG) is the major glycoconjugate in promastigotes cell wall, consisting of a hexasaccharide core including a galactofuranose motif. Galactofuranose is absent in mammalian membranes, thus could be a therapeutic target. First, this work studied the galactofuranosyl-transferases involved in the metabolism of this furanose, as well as a mutase, also necessary for the metabolism of galactofuranose. Once targets were identified in the two parasitic stages, galactofuranose derivatives were tested for antileishmanial activity on promastigotes and amastigotes forms of Leishmania donovani. A compound showed interesting results and has been studied further, the n-octyl-galactofuranose (Galf). Different techniques have been used to characterize its mode of action on promastigotes and amastigotes: electron paramagnetic resonance, transmission electron microscopy, nuclear magnetic resonance or flow cytometry. Infected macrophages treated with Galf were able to produce oxygen derivatives species, leading us to look at the immunomodulatory capacity of Galf derivatives. Thus, the last part of this work focused on the study of macrophage polarization by galactofuranosides on an in vitro model of human macrophages. We were able to show that Galf stimulates macrophages towards M1 polarization, which could explain the decreased growth of amastigotes inside macrophage cells
44
Zark, S. "Mechanisms of immunomodulation by the periodontal pathogen Porphyromonas gingivalis". Thesis, Queen's University Belfast, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546428.
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Morris, Rebecca Jane. "Immunomodulation of the cellular immune response by human cytomegalovirus". Thesis, Cardiff University, 2004. http://orca.cf.ac.uk/55574/.
Testo completoAbstract (sommario):
HCMV is a ubiquitious p herpesvirus that usually causes asymptomatic primary infection. Individuals infected with HCMV mount a strong immune response that suppresses persistent viral replication and is paramount for the prevention of HCMV disease. HCMV encodes a large number of immunomodulatory functions that modulate both the innate and adaptive arms of the immune system. The project undertaken in this thesis was to investigate and characterise immunomodulatory functions encoded by HCMV. A novel and highly efficient method of Natural Killer (NK) cell cloning was developed to investigate modulation of the NK response by HCMV. This technology was utilised to further investigate the finding that CD94/NKG2A+ NK cells are inhibited by UL40-stabilised HLA-E. Analyses of polyclonal NK cell responses and NK clones showed that more CD9410 than CD94hl NK cells were activated by HCMV strain AD169 in comparison to uninfected targets. Flow cytometry showed that there was an increase in the frequency of NK cells expressing the activatory receptor CD94/NKG2C and a decrease in the frequency of cells expressing the inhibitory receptor CD94/NKG2A in HCMV seropositive individuals. The response of NK clones expressing CD94/NKG2A or CD94/NKG2C to targets infected with strain AD169 or RAdUL40 indicated that some CD94/NKG2A clones can be inhibited by gpUL40 while some CD94/NKG2C clones can be activated by gpUL40. Comparative analysis of NK responses to HCMV strain Towne, indicated that strain Towne encoded a novel NK modulatory function that differentially targeted the CD94to and CD94hi NK cell subset in certain individuals. HCMV strain Toledo is known to encode a powerful inhibitor of NK function. Analysis of polyclonal NK cell responses mapped this inhibitory function to gpUL141. In depth analysis of 98 NK clones demonstrated that gpUL141 inhibited a large proportion of NK cells and this was independent of CD94 expression. The initial aim of this study was to characterise the immunomodulatory function of pp65, an HCMV protein that has previously been shown by others to abrogate recognition of HCMV infected cells by HCMV-IE1 specific CTL. Fluorescence microscopy showed that pp65 did not alter the localisation of IE1 and a yeast two-hybrid assay indicated that there was no direct interaction between these 2 proteins. A functional assay using IE1 specific CTL was not performed because sufficient numbers of peptide specific CTL could not be cultured. Nevertheless, this study has contributed to the characterisation of powerful HCMV immunomodulatory functions that selectively target NK cell subsets and are sufficient to alter frequencies of cells in the innate immune system. The results presented here enhance our understanding of HCMV pathogenesis, the regulation of NK cell function and the biology of the innate immune system.
46
Quentin, Julie. "Immunomodulation de l'arthrite expérimentale par les cellules dendritiques tolérogènes". Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON1T018/document.
Testo completoAbstract (sommario):
Immunomodulation de l'arthrite expérimentale par les cellules dendritiques tolérogènes. Les cellules dendritiques (DCs) sont des cellules présentatrices d'antigènes jouant un rôle clé dans l'initiation et la modulation des réponses immunitaires. En effet, en parallèle de leur capacité à initier une réponse immunitaire adaptative, les DC sont également impliquées dans les mécanismes de tolérance périphérique. Elles sont utilisées depuis 10 ans maintenant en clinique dans des stratégies thérapeutiques anti-tumorale et leurs propriétés tolérogènes ouvrent aujourd'hui leur champ d'applications à des pathologies autoimmunes, l'asthme et la transplantation afin de restaurer une homéostasie de la réponse immune. Les objectifs de ma thèse ont consisté à :- renforcer le potentiel tolérogène des DCs par manipulation in vitro- tester la capacité de DCs tolérogènes à induire une protection de l'arthrite expérimentale- identifier les mécanismes cellulaires et moléculaires impliqués dans la tolérance induite par les DCs. Mon travail de thèse a permis de montrer l'efficacité de la vaccination de souris arthritiques avec des DCs immatures conservant leurs propriétés tolérogènes in vitro et in vivo, grâce au traitement préalable avec un agent immunosuppresseur, la rapamycine. L'injection répétée de DCs immatures induit la génération de lymphocytes T régulateurs CD4+ CD49b+ sécrétant de l'IL-10 ayant de fortes capacités immunosuppressives. Ce projet a permis de mettre en évidence l'efficacité des DCs dans le traitement d'une pathologie autoimmune déjà établie et l'implication d'une population cellulaire régulatrice originaleTolerogenic dendritic cells for immumodulation in experimental arthritis.Dendritic cells (DCs) are the most potent antigen-presenting cells that play critical roles in the initiation and regulation of immune responses. Based on their tolerogenic properties, DCs offer potential as therapeutic tools to ameliorate or prevent graft rejection or graft-versus-host disease, or to treat autoimmune disorders.The objectives of my PhD consisted to:- reinforce the tolerogenic potential of DCs by in vitro handling.- assess the capacity of such tolerogenic DCs to induce a protective response in experimental autoimmune arthritis- identify cellular and molecular mechanisms implied in the tolerogenic DCs-induced protectionOur results suggest that, in contrast with conventional DCs, the rapamycin-conditioned iDCs maintain their tolerogenic potential upon injection in inflammatory settings and are able to dampen an already Th1-primed immune response, conferring a protection from arthritis. The protection of the mice was associated with an expansion of the IL-10-secreting CD49b+ Treg in the spleen and liver of the injected mice and a decrease of the Th1 immune response. These results underscore the therapeutic potential of tolerogenic DCs in an established autoimmune disease as well as the anti-inflammatory potential of the CD49b+ Treg cell population induced following DC vaccination
47
Nikolic, William Veljko. "Immunomodulation as a potential therapeutic approach for Alzheimer's disease". [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002539.
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Nikolic, William Veljko. "Immunomodulation As A Potential Therapeutic Approach For Alzheimer’s Disease". Scholar Commons, 2008. https://scholarcommons.usf.edu/etd/429.
Testo completoAbstract (sommario):
Alzheimer's disease (AD) is the most prevalent form of progressive dementia and is characterized by the accumulation of amyloid beta (Aß) peptide in the brain and in the cerebral vessels forming cerebral amyloid angiopathy (CAA). As previously reported, an active immunization strategy of mice with Aß1-42 peptide results in decreased Th1 and increased Th2 cytokine responses as well as an effectively clearance of CNS Aß. This approach has also yielded favorable results for many patients, unfortunately, a small percentage of these study participants developed severe aseptic meningoencephalitis likely secondary to CNS invasion of activated T-cells. We have previously demonstrated that disruption of CD40-40L pathway reduces Aß plaque load, promotes Th2 response, and rescues from cognitive impairments. However, direct blockage of the CD40 pathway by passive vaccination with anti-CD40L antibody leads to immunosupression. Therefore, in its current form this therapeutic strategy poses an unacceptable risk to the recipient of treatment, aged individual. For those reasons, the identification and characterization of alternative modulators/inhibitors of CD40 signaling may be necessary for the development of safe and effective AD immunotherapy.
This proposal introduces novel immunomodulatory therapies that are based on previous vaccination strategies or cell based therapies across medial field. We showed that transcutaneous vaccination can both be efficacious and safe, thus clearly demonstrating that the right combination of the antigens, adjuvants, and the routes of administration are crucial for the right vaccine. Furthermore, we demonstrated that the effects of current Aß vaccine strategies could be enhanced by a simultaneous blockade of CD40-40L signaling. As an alternative approach, we explored the possibility of cell-based therapies and showed that human umbilical cord blood cells, which are currently used as a treatment for systemic lupus erythematosus and leukemia, and currently investigated against stroke, amyotropic lateral sclerosis, age-related macular degeneration, multiple sclerosis, and Parkinson's disease, and showed that not just they improved the AD like pathology in transgenic animals but altered both the brain and peripheral inflammation levels. Lastly, we discussed the involvement of microglia, one of the key players in both AD pathogenesis and Aß clearance and suggesed that microglia in actuality has a continuum of physiological activation states that contribute to proinflammation, antiinflammation, and phagocytosis.
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Palmerini, Emanuela <1975>. "New therapeutic approaches in sarcoma: Immunomodulation and tumor microenvironment". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amsdottorato.unibo.it/8393/1/Tesi%203%20MAR%2018%20no%20pub%20awards.pdf.
Testo completoAbstract (sommario):
High‐grade sarcomas are a heterogeneous group of aggressive tumors arising in bone and soft tissues. They are usually treated with surgery combined in some cases with chemotherapy. Drugs active in osteosarcoma include adriamycin (ADM), cisplatin (CDDP), ifosfamide (IFO) and methotrexate (MTX), while ADM and IFO represent standard chemotherapy for synovial sarcomas. The survival of sarcomas has minimally improved in the past decades, and after relapse treatment options are limited.
Tumors grow within an intricate network of epithelial cells, vascular and lymphatic vessels, cytokines, chemokines and infiltrating immune cells. T‐ lymphocyte and antigen‐presenting cells (APCs) interactions are bi‐directional and mediated by ligands such as programmed cell death ligand 1 (PD‐L1) on APCs and PD1 on lymphocytes. PD‐L1 is expressed also by several tumors. PD‐1 inhibitors such as pembrolizumab or nivolumab have been approved for many tumors and PD‐L1 expression on tumoral cells has been associated with response in some of the studies. However, few data on the prognostic and predictive role of infiltrating immune cells and PD‐1/PD‐L1 system in sarcoma are available.
Stromal cells present in the tumor microenvironment express high levels of CXCL12 protein, directly stimulating proliferation and migration of CXCR4‐expressing cancer cells. CXCR4/CXCL12 signalling therefore is an attractive therapeutic target in cancer, since CXCR4 inhibition might sensitize cancer cells to conventional chemotherapy.
Finally, another key element of the tumor microenvironment involves its vasculature. Tumor angiogenesis is related to suppression of T cell‐mediated tumor rejection. There are numerous examples that demonstrate a simultaneous activation of angiogenesis and immunosuppression. The overall goal of this project is to characterize the osteosarcoma and synovial sarcoma tumor microenvironment, to assess how the infiltrating immune cells can affect the prognosis of patients and to assess the activity of immune modulating (anti‐PD‐1), migration inhibitors (anti‐CXCR4) and antiangiogenetic (anti‐VEGFRs, anti‐PDGFRs) compounds in an in vitro sarcoma model.
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Whittall, Christine Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma". Awarded By:University of New South Wales. Biotechnology & Biomolecular Sciences, 2009. http://handle.unsw.edu.au/1959.4/44957.
Testo completoAbstract (sommario):
Pseudomonas aeruginosa is a significant pathogen of immunocompromised individuals, and the main mechanism by which it mediates virulence is through the coordination of gene expression by an intricate quorum sensing system. One of the signalling molecules of this system, N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) has been shown to have immunomodulatory capabilities, discrete to its quorum sensing role. While the general focus of research in this area is on the physiological outcomes of this interaction on cell function, there is currently little concrete evidence identifying the receptor(s) for OdDHL in mammalian cells, and hence the biochemical mechanism behind the immunomodulation caused by OdDHL remains largely unknown. This study identifies peroxisome proliferator-activated receptor γ (PPARγ) as a mammalian target for OdDHL. PPARγ is a mammalian transcription factor involved in fatty acid metabolism and is heavily involved in the inflammatory response, being a negative regulator of inflammation. It is shown here that OdDHL is able to instigate signalling through PPARγ by activation of the ligand binding domain (LBD), suggesting that OdDHL may act as a PPARγ agonist. OdDHL is able to compete with the PPARγ agonist, rosiglitazone, causing a relative antagonism of PPARγ activity when given in tandem with the agonist. The bacterial signalling molecule is unable to displace the irreversible PPARγ antagonist GW9662. This effect on PPARγ is specific to OdDHL, as the smaller P. aeruginosa signalling molecule, N-butyryl-L-homoserine lactone had no significant effect on PPARγ activation. In order to confirm PPARγ as a putative receptor for OdDHL in mammalian cells, initial experiments were undertaken to optimise conditions to produce PPARγ LBD protein for binding interaction studies. The fidelity of the protein sequence was established and expression of the protein in an appropriate vector was confirmed. The protein produced was insoluble and hence not functional for binding studies, suggesting that additional optimisation of expression conditions, or manipulation and refolding of the protein is necessary before further experimentation can take place. The identification of PPARγ as a receptor for OdDHL in mammalian cells is an important step in understanding the nature and scope of the interaction between OdDHL and host cell physiology, especially the significance of this interaction during P. aeruginosa infection. Continuation of this research, in particular completion of protein-ligand binding studies between OdDHL and PPARγ has the potential to clarify the significance of the immunomodulation caused by OdDHL, while providing us with a platform from which we may exploit it.