Immunity to heat shock proteins and neurological disorders of women.
Stress or heat shock proteins are constitutively expressed in normal CNS tissues in a variety of cell types (oligodendrocytes, astrocytes, and neurons). Their presence may protect cells from various stresses, such as hypoxia, anoxia, and excessive excitatory stimulation. Increased amounts of hsp are expressed in various cells of the CNS during acute toxic-metabolic states and in chronic degenerative and inflammatory diseases. Increased expression of hsp may lead to immune responses to these proteins. Antibodies to mycobacterial hsp bind to normal human myelin and to oligodendrocytes in regions of MS demyelination. Cellular immune responses to hsp occur with increased frequency and magnitude in persons with MS, especially those with recent onset of disease. In addition, there are populations of T cells expressing gamma/delta T cells in the brains and spinal fluids of persons with MS, suggesting an in situ immune response to hsps. Humoral immune responses to hsp are found in CSF, but no disease specificity has been documented. Some myelin proteins have sequence homology with particular hsps. One instance is the homology between a peptide of mycobacterial Hsp65 and the myelin protein CNP. Our data on EAE suggest that immune responses to either cross-reactive hsp epitopes or whole hsp can modify the course of both acute and chronic relapsing EAE. In addition, the severity and frequency of environmental exposure to infectious agents can modify the course of EAE, possibly by altering the patterns of immune response to hsp. Finally, tolerance to the small hsp, alpha B-crystallin, a putative autoantigen in persons with MS, alters the course of relapsing EAE, supporting its role in chronic, autoimmune CNS disease. Modifying immune responses to hsp may be a potential new treatment option for persons with MS.
Birnbaum
G
G
Department of Neurology, University of Minnesota, School of Medicine, Minneapolis, USA. birnb001@tc.umn.edu
Kotilinek
L
L
D001327:Autoimmune Diseases / Q000276:immunology*; D004679:Encephalomyelitis / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*; D012737:Sex Factors
D006360:Heat-Shock Proteins