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Memorial University - Electronic Theses and Dissertations 4
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Document Description
TitleLooks that kill : accessory receptor phenotypes and the cytolytic activities of cytotoxic T-lymphocytes and natural killer cells
AuthorParsons, Matthew S. (Matthew Sidney), 1984-
DescriptionThesis (M.Sc.)--Memorial University of Newfoundland, 2010. Medicine
Date2010
Paginationxiii, 106 leaves : ill.
SubjectCell-mediated cytotoxicity; Killer cells; T cells--Receptors;
Subject.MESHAntibody-Dependent Cell Cytotoxicity; Killer Cells, Natural; T-Lymphocytes, Cytotoxic;
DegreeM.Sc.
Degree GrantorMemorial University of Newfoundland. Faculty of Medicine
DisciplineMedicine
LanguageEng
NotesIncludes bibliographical references
AbstractNatural killer (NK) cells and cytotoxic T-lymphocytes (CTL) express activating and inhibitory accessory receptors specific for class I human leukocyte antigens (HLA-I) or stress induced antigens. Signals from the ligation of these receptors are integrated to modulate T-cell mediated cytolysis and to determine NK cell cytolytic activity. Signals generated from the ligation of inhibitory receptors also mediate several other functions, such as reducing apoptosis and activation induced cell death. In mouse models these inhibitory receptors 'license' NK cells. NK cells expressing an inhibitory receptor, from mice expressing the ligand, have the ability to mediate both general and antibody-dependent cellular cytotoxicity (ADCC). NK 'licensing' also appears to account for human NK cell activity. Data from two studies have demonstrated a role for licensing of general NK cell mediated cytolysis, but data regarding ADCC are conflicting. As activating and inhibitory receptors are of much importance to both NK and T-cells, we investigated the potential expression and/or involvement of these receptors in the HLA-I unrestricted cytolysis mediated against CD4+ T-lymphocytes by a subset of CD8+ CTL in HIV infection. The TCR-dependent and HLA-I-independent CTL demonstrated a phenotype that matches generalized changes on CD8+ T-lymphocytes in progressive HIV infection. The CTL that killed activated uninfected CD4+ T-lymphocytes lacked expression of the CD56 marker and the inhibitory NKG2A receptor. We also investigated the role of NK cell 'licensing' for ADCC in humans. The potency of NK cells expressing the inhibitory KIR3DL1 receptor was investigated in samples taken from individuals expressing and not expressing the HLA-BW4 ligand. Our results suggest NK cell licensing is involved in ADCC.
TypeText
FormatImage/jpeg; Application/pdf
SourcePaper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries
Local Identifiera3302078
RightsThe author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
CollectionElectronic Theses and Dissertations
Scanning StatusCompleted
PDF File(12.53 MB) -- http://collections.mun.ca/PDFs/theses/Parsons_MatthewS.pdf
CONTENTdm file name142372.cpd