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DC Field | Value | Language |
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dc.contributor.advisor | Kishore, U | - |
dc.contributor.advisor | Tsolaki, A | - |
dc.contributor.author | Qaseem, Asif Shehzad | - |
dc.date.accessioned | 2017-01-18T14:54:31Z | - |
dc.date.available | 2017-01-18T14:54:31Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/13893 | - |
dc.description | This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London | en_US |
dc.description.abstract | Lung surfactant protein D (SP-D) is a soluble pattern recognition and innate immune molecule, which has been shown to be protective against lung infection, allergy, asthma and inflammation. SP-D is composed of an N-terminal collagen region and a homotrimeric, C-terminal carbohydrate binding domain (CRD). A recombinant form of trimeric CRD region (rhSP-D) has been shown to offer protection against asthma and inflammation in murine models by bringing down IgE levels, eosinophilia, and causing T helper cell polarisation from a pathogenic Th2 to a protective Th1 phenotype. Thus, rhSP-D can provide a therapeutic effect by dampening asthmatic symptoms in mice. The therapeutic mechanisms include inhibition of allergen-IgE binding and histamine release by sensitized mast cells, downregulation of allergen/antigen-specific IgG and IgE antibodies, pulmonary and peripheral eosinophilia, a shift from Th2 to Th1 cytokine response, interference with airway remodelling processes, and apoptosis- induction in sensitised eosinophils from allergic patients. The majority of the ex vivo and in vivo studies where a therapeutic effect of rhSP-D has been reported can not be explained by hitherto described candidate receptor involvement, especially CD91-calreticulin complex that requires collagen region for its cellular response. Thus, it is pertinent to examine at the cellular and molecular level how a trimeric lectin domain of human SP-D modulates immune cells. This was achieved by firstly expressing, purifying and characterising the recombinant rhSP-D and examining the interaction of rhSP-D with various immune cells such as macrophages, which are potent antigen presenting cells and play a crucial role in the maintenance of the inflammatory and humoral response to allergens. The highlight of this study is the demonstration that rhSP-D interferes with the co-operative binding of allergen-IgE complexes to B cells, and also downregulates expression of CD23, a low affinity IgE receptor (FcεRII), found on B cells. This suggests that inhibition of IgE-facilitated antigen presentation may represent a mechanism whereby SP-D suppresses Th2-driven allergic inflammation. In addition, this study is also the first to establish the calcium-dependent interactions between rhSP-D, CD23 and CD21. The possibility of formation of a trimolecular complex on the B cell surface may account for the suppression of IgE in therapeutic murine models since rhSP-D may interfere with CD21-CD23 mediated IgE production by primed B cells. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Brunel University London | en_US |
dc.relation.uri | http://bura.brunel.ac.uk/bitstream/2438/13893/1/FulltextThesis.pdf | - |
dc.subject | Immunology | en_US |
dc.subject | Asthma | en_US |
dc.subject | SP-D | en_US |
dc.subject | Allergy | en_US |
dc.subject | Molecular biology | en_US |
dc.title | Modulation of immune cell functions by human lung surfactant protein SP-D in allergic asthma | en_US |
dc.type | Thesis | en_US |
Appears in Collections: | Biological Sciences Dept of Life Sciences Theses |
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File | Description | Size | Format | |
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FulltextThesis.pdf | 3.3 MB | Adobe PDF | View/Open |
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