The role of myelin antigen transfer in the CNS in the etiology of multiple sclerosis

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dc.contributor.advisorForsthuber, Thomas
dc.contributor.authorMurphey, Cathi L.
dc.contributor.committeeMemberHeidner, Hans
dc.contributor.committeeMemberWormley, Floyd
dc.contributor.committeeMemberKraig, Ellen
dc.contributor.committeeMemberGaufo, Gary
dc.date.accessioned2024-02-12T18:30:24Z
dc.date.available2024-02-12T18:30:24Z
dc.date.issued2010
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractMultiple Sclerosis (MS) is a debilitating autoimmune disease that is characterized by demyelination and inflammatory lesions of the central nervous system. The axonal damage and impairment of motor, autonomic and cognitive function lead to significant disability. It is well known that the acute lesions are mediated by CD4+ T helper type cells and CD8+ cytotoxic T cells. Myelin antigen is presented to T cells under inflammatory conditions but it remains unknown whether antigen is presented constitutively at low levels under conditions of non-inflammation in the CNS. Our data show that in the naive brain, the only antigen presenting cells (APC) present in sufficient quantity and capable of presenting antigen to T cells are microglia. We demonstrate that microglia are loaded with myelin antigen in the naive brain and after immunization are able to present antigen immediately for T cell activation. Furthermore, inflammatory mediators such as cytokines have been shown to play a major role in the pathology and tissue damage associated with MS. It remains to be proven which pro-inflammatory cytokines are critical for the ensuing inflammation and tissue damage. Our research shows that when IFN-gamma is removed either though gene knockout mice or neutralizing antibody, that experimental autoimmune encephalomyelitis (EAE) is exacerbated in the mouse model of MS. Interesting, we found an inverse correlation with the presence of IFN-gamma and myelin antigen loading and disease severity. Collectively these data show that microglia may be the first cell type to activate CD4+ T cells and that IFN-gamma may play a protective role in EAE. Our long term goal is to better understand the mechanism of neuroantigen transfer and the requisite inflammatory mediators in order to facilitate the development of therapeutic agents for treatment of this disease.
dc.description.departmentIntegrative Biology
dc.format.extent135 pages
dc.format.mimetypeapplication/pdf
dc.identifier.isbn9781124188416
dc.identifier.urihttps://hdl.handle.net/20.500.12588/4825
dc.languageen
dc.subjectautoimmunity
dc.subjectmultiple sclerosis
dc.subject.classificationCellular biology
dc.subject.classificationMolecular biology
dc.subject.classificationImmunology
dc.titleThe role of myelin antigen transfer in the CNS in the etiology of multiple sclerosis
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentIntegrative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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