Multiple Sclerosis: Immunology, Pathology and Pathophysiology

Cover Page......Page 1
Title Page......Page 5
ISBN 1888799625......Page 6
Dedication......Page 7
Contents (with page links)......Page 9
1 Developments in Multiple Sclerosis: Research Overview......Page 17
I MORPHOLOGIC SUBSTRATES OF DEMYELINATION......Page 21
2 Morphology of Oligodendrocytes and Myelin......Page 23
SUBTYPES OF OLIGODENDROCYTES......Page 24
ULTRASTRUCTURE OF OLIGODENDROCYTES......Page 26
ORIGINS AND LINEAGES OF OLIGODENDROCYTES......Page 28
MYELIN......Page 31
MATURATION OF OLIGODENDROCYTES AND FORMATION OF THE MYELIN SHEATH......Page 34
STRUCTURE OF THE MYELIN SHEATH......Page 36
STRUCTURE AND CLASSIFICATION......Page 41
PHAGOCYTIC ROLE OF ASTROCYTES......Page 42
Role in Formation of the Blood–Brain Barrier......Page 43
Role in Synaptic Regulation, Function, and Maintenance of Postsynaptic Specializations......Page 44
SUMMARY......Page 45
CNS MYELIN PROTEINS: STRUCTURE AND FUNCTION......Page 47
Myelin Basic Proteins......Page 51
Myelin Proteolipid Proteins......Page 52
Myelin-Oligodendrocytic Glycoprotein......Page 53
Localization of Proteins in Incisures, Radial Components, and Paranodal and Nodal Regions of Myelin......Page 54
Enzymes and Receptors in Myelin......Page 55
CNS Myelin Lipids......Page 56
STRUCTURAL–MOLECULAR RELATIONSHIPS Interactions among Lipids and Proteins in the Myelin Membrane......Page 58
Assembly of CNS Myelin......Page 59
Regulation of Myelination......Page 60
II EXPERIMENTAL ASPECTS OF DEMYELINATION......Page 67
5 The Nature of Immunologic Privilege in the Central Nervous System......Page 69
BBB AND THE NATURE OF IMMUNOLOGIC PRIVILEGE IN THE CNS Traditional View of the BBB......Page 70
The Importance of the BBB in Maintaining Immune Privilege in the CNS......Page 72
T LYMPHOCYTES IN THE CNS......Page 73
Adhesion Molecule Expression on Nonactivated and Inflamed Brain Endothelium......Page 76
Normal Immune Surveillance and Pathologic Traffic of Immune Cells into the CNS......Page 78
ANTIGEN PRESENTATION IN THE CNS BY CNS-RESIDENT-CELLS......Page 80
Antigen-specific Activation of T-cells......Page 81
Antigen Presentation at the BBB......Page 82
Antigen Presentation in the Brain Parenchyma by Residential APCs......Page 85
Astrocytes as Immunocompetent Cells......Page 87
CONCLUSION......Page 88
EAE: A CD4+ T-CELL–MEDIATED DEMYELINATING DISEASE......Page 95
MHC RESTRICTION AND DISEASE SUSCEPTIBILITY......Page 96
T-CELL RECEPTOR SPECIFICITY AND USAGE......Page 97
T-CELL COSTIMULATION......Page 99
CYTOKINES......Page 101
CHEMOKINES......Page 107
TOLERANCE......Page 108
EPITOPE SPREADING......Page 109
THEILER MURINE ENCEPHALOMYELITIS VIRUS-INDUCED DEMYELINATING DISEASE......Page 110
CONCLUSION......Page 111
EAE AND SERUM DEMYELINATING FACTORS Characterization of Antimyelin Factors......Page 121
Specificity of Antimyelin Factors......Page 122
Antibodies to CMIP and MOG......Page 123
MS AND SERUM DEMYELINATING FACTORS......Page 124
POSSIBLE SIGNIFICANCE OF ANTIMYELIN FACTORS......Page 125
INFECTIOUS AGENTS OF HUMANS KNOWN TO CAUSE PNS OR CNS DEMYELINATION......Page 129
Postinfectious Immune–mediated Demyelination......Page 130
Overview of Potential Mechanisms of Virus-Induced CNS Demyelination......Page 131
Epidemiologic Evidence......Page 132
PATHOGENS OF CURRENT INTEREST IN MS Human Herpes Virus-6......Page 133
EBV and Other Herpes Viruses......Page 134
Nonviral Agents......Page 135
CONCLUSION......Page 136
9 Viral Demyelinating Diseases in Experimental Animals......Page 141
BACKGROUND Theiler’s Murine Encephalomyelitis Virus (TMEV)......Page 142
Mouse Hepatitis Virus (MHV)......Page 143
TMEV—Nude and SCID Mice......Page 144
MHV—Nude and SCID Mice......Page 145
Antibodies—Protection and Clearance......Page 146
CONCLUSION......Page 147
BIOLOGY OF CHLAMYDIAL INFECTION......Page 151
Acute Neurologic Syndromes Associated with C. pneumoniae Infection......Page 152
EVIDENCE OF CHRONIC PERSISTENT INFLAMMATION IN THE CNS OF PATIENTS WITH MS......Page 154
INFECTION, IMMUNITY, AND AUTOIMMUNITY: A SYNTHESIS OF MECHANISMS INVOLVED IN CHLAMYDIAL-ASSOCIATED CNS INFECTIOUS DISEASE......Page 155
MOLECULAR MIMICRY......Page 156
CONCLUSION......Page 157
III CYTOKINES, CHEMOKINES, AND INTERFERONS......Page 159
CYTOKINE FUNCTIONS......Page 161
REGULATION OF THE CYTOKINE RESPONSE IN T-CELLS......Page 163
GENERAL RESPONSE OF CYTOKINES IN EAE AND MS Cytokines Involved in EAE......Page 164
Cytokines In Multiple Sclerosis......Page 168
CONCLUSION......Page 170
MS Neuropathology and The Pathogenesis of Disability......Page 175
CHEMOKINES AND LEUKOCYTE TRAFFICKING IN THE CNS Chemokines and Leukocyte Trafficking......Page 176
Chemokine Receptors......Page 179
Chemokines, Their Receptors, and Immune Responses......Page 181
Transgenic and Knockout Models......Page 182
Inflammatory Disease Models......Page 183
Clinical Studies......Page 184
CONCLUSION......Page 185
SOURCES OF INTERFERON......Page 191
STRUCTURE AND BIOLOGIC EFFECTS......Page 192
T-Cell Activation......Page 193
Induction of Cytokines Shift......Page 194
at the BBB......Page 195
Effects in the CNS......Page 196
IV PATHOLOGY......Page 199
14 The Pathology of Multiple Sclerosis and Its Variants......Page 201
ETIOLOGY......Page 202
PATHOLOGY OF RELAPSING REMITTING MULTIPLE SCLEROSIS......Page 203
Pattern 3: Active Demyelination with an Infiltrate of T Lymphocytes and Activated Macrophages and Microglia......Page 204
THE ACUTE PLAQUE......Page 205
CHRONIC ACTIVE AND INACTIVE PLAQUES......Page 206
GRAY MATTER PLAQUES......Page 207
REMYELINATION......Page 208
SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS......Page 209
ACUTE DISSEMINATED ENCEPHALOMYELITIS......Page 210
STRUCTURES RESEMBLING INFECTIOUS AGENTS IN MS TISSUES......Page 211
CONCLUSION......Page 212
The Earliest MS Lesion—Before Those Visualized by Conventional MRI......Page 215
The Early Inflammatory MS Lesion......Page 216
Lesion Regression Stages......Page 219
The Chronic MS Lesion—T2 Footprints......Page 220
THE NORMAL APPEARING WHITE MATTER IN MS......Page 222
NEURONAL TRACT DEGENERATION IN MS......Page 223
MORE DIFFUSE AND GLOBAL EFFECTS OF INJURY—CNS ATROPHY......Page 224
OTHER SIGNS OF NEURONAL DEGENERATION—T2-SHORTENED (BLACK-T2) AREAS......Page 225
CONCLUSION......Page 227
RESOLUTION OF THE INFLAMMATORY RESPONSE......Page 231
REMYELINATION......Page 232
RESTORATION OF CONDUCTION IN DEMYELINATED FIBERS......Page 233
NEURAL PLASTICITY WITH RESTORATION OF FUNCTION......Page 236
CONCLUSION......Page 237
Index......Page 239