Interactions Between the Human Immune System and Antigens in the Nervous System

McFarland, Henry F.

Abstract

The goal of this project is to examine the manner in which immunologic mechanisms may contribute to diseases of the nervous system. The cellular and humoral immune response to putative antigens and possible immunopathologic diseases such as multiple sclerosis (MS) are being studied. Included in these studies have been examinations of the immune response to viruses which can commonly infect the nervous system and which could be related to the induction of immunopathologic disease processes. In addition, the immune response to antigens of myelin such as myelin basic protein and proteolipid protein which may represent targets of immune-mediated diseases of myelin, has been studied. The emphasis in these studies has been on identifying differences in these immunologic responses which may occur in patients with diseases of the nervous system such as MS, as compared to healthy individuals. Particular attention has been given to examining the influence of genetic makeup on both the induction and effector phases of these immune responses. In particular, the role of HLA molecule genes and T-cell receptor investigated.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Intramural Research (Z01)
• Project #: 1Z01NS002205-17
• Application #: 3846174
• Support Year: 17
• Fiscal Year: 1992

Institution

• Name: National Institute of Neurological Disorders and Stroke
• Country: United States

Publications

Lunemann, Jan D; Kamradt, Thomas; Martin, Roland et al. (2007) Epstein-barr virus: environmental trigger of multiple sclerosis? J Virol 81:6777-84

Martin, Roland; Bielekova, Bibiana; Hohlfeld, Reinhard et al. (2006) Biomarkers in multiple sclerosis. Dis Markers 22:183-5

Sospedra, Mireia; Muraro, Paolo A; Stefanova, Irena et al. (2006) Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the multiple sclerosis-associated HLA-DR2 haplotype. J Immunol 176:1951-61

Cassiani-Ingoni, Riccardo; Cabral, Erik S; Lunemann, Jan D et al. (2006) Borrelia burgdorferi Induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression. J Neuropathol Exp Neurol 65:540-8

Cassiani-Ingoni, Riccardo; Coksaygan, Turhan; Xue, Haipeng et al. (2006) Cytoplasmic translocation of Olig2 in adult glial progenitors marks the generation of reactive astrocytes following autoimmune inflammation. Exp Neurol 201:349-58

Bielekova, Bibiana; Catalfamo, Marta; Reichert-Scrivner, Susan et al. (2006) Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 103:5941-6

Muraro, Paolo A; Cassiani-Ingoni, Riccardo; Chung, Katherine et al. (2006) Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation and remission in a patient with multiple sclerosis. J Neuroimmunol 171:177-83

Sospedra, Mireia; Martin, Roland (2006) Molecular mimicry in multiple sclerosis. Autoimmunity 39:3-8

Lunemann, Jan D; Edwards, Nancy; Muraro, Paolo A et al. (2006) Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis. Brain 129:1493-506

Cassiani-Ingoni, Riccardo; Greenstone, Heather L; Donati, Donatella et al. (2005) CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell-cell fusion. Glia 52:252-8