1;Molecular Basisof Multiple Sclerosis;2 1.1;Preface;4 1.2;Contents;5 2;Neuro-Immune Crosstalk in CNS Diseases;7 2.1;1 Introduction;7 2.2;2 Molecular Aspects of Neuro-Immune Crosstalk;8 2.2.1;2.1 Neurotrophic Factors;9 2.2.2;2.2 Cytokines;12 2.2.3;2.3 Chemokines;13 2.3;3 Functional Aspects of Neuro-Immune Crosstalk;14 2.4;4 Implications for Inflammatory CNS Disease;16 2.4.1;4.1 CNS Disease with Primary Inflammation;16 2.4.2;4.2 CNS Disease with Secondary Inflammation;18 2.5;5 Perspectives;19 2.6;References;20 3;Role of NK Cells and Invariant NKT Cells in Multiple Sclerosis;27 3.1;1 Introduction;27 3.2;2 NK Cells and MS;29 3.2.1;2.1 General Properties of NK Cells;29 3.2.2;2.2 NK Cell in MS;31 3.2.2.1;2.2.1 Protective Role of NK Cells in EAE;32 3.2.2.2;2.2.2 Ex Vivo Analysis Revealed an Alteration of NK cells in MS;33 3.3;3 iNKT Cells in MS;35 3.3.1;3.1 What Is iNKT Cell?;35 3.3.1.1;3.1.1 General Properties of Invariant NKT (iNKT) Cells;35 3.3.1.2;3.1.2 iNKT Cells and Their Ligands;36 3.3.2;3.2 Studies of iNKT Cells in MS;38 3.3.3;3.3 iNKT Cells as a Therapeutic Target in MS/EAE;39 3.4;4 MR1- Restricted Invariant T Cells in MS;41 3.5;5 Concluding Remarks;42 3.6;References;42 4;Potential Triggers of MS;48 4.1;1 Introduction;48 4.2;2 Viral Association with Demyelination;52 4.3;3 Torque Teno Virus and MS;53 4.4;4 Epstein-Barr Virus and MS;54 4.5;5 HHV-6 and MS;56 4.6;6 Basic Animal Model: Viral Persistence Within the CNS;57 4.7;7 Prime/Challenge Model: Acute Peripheral Infection;59 4.8;8 Conclusion;64 4.9;References;65 5;Prospects for Antigen-Specific Tolerance Based Therapies for the Treatment of Multiple Sclerosis;70 5.1;1 Introduction;70 5.2;2 Monoclonal Antibody Induced Tolerance;73 5.3;3 Antigen Specific Induced Tolerance Induction;74 5.3.1;3.1 Altered Peptide Ligand Induced Tolerance;74 5.3.2;3.2 Mucosal Tolerance;76 5.3.3;3.3 Soluble Peptide Tolerance;77 5.3.4;3.4 ECDI-Peptide-Coupled Cell Induced Tolerance;78 5.4;4 Conclusions;82 5.5;References;83 6;Immuno-Therapeutic Potential of Haematopoietic and Mesenchymal Stem Cell Transplantation in MS;89 6.1;1 Bone-Marrow-Derived Stem Cells;90 6.1.1;1.1 The Haematopoietic Niche;90 6.1.2;1.2 Haematopoietic Stem Cells and Their Properties;91 6.1.3;1.3 Identification of Mesenchymal Stem Cells and Their Role in Bone Marrow;92 6.2;2 Haematopoietic Stem Cell Transplantation as a Therapy for Autoimmune Disease;93 6.2.1;2.1 Autologous HSCT for MS: Clinical Results;93 6.2.2;2.2 Unraveling the Effects of Autologous HSCT on the Immune System;94 6.2.3;2.3 Immune Regeneration After HSCT;95 6.3;3. MSCs: Potential Role in Immunotherapy of MS;99 6.3.1;3.1 MSCs Effect on Immune cells;99 6.3.2;3.2 MSCs In vivo Effects in Preclinical Model of CNS Diseases;100 6.3.3;3.3 Clinical Applications of MSCs;101 6.4;4 Conclusions;102 6.5;References;103 7;Immune-Mediated CNS Damage;110 7.1;1 Introduction;110 7.2;2 Innate Immunity in Multiple Sclerosis;113 7.2.1;2.1 Microglia Activation;113 7.2.2;2.2 Microglial Pattern Recognition Receptors and Neurotoxicity;115 7.2.2.1;2.2.1 Toll-Like Receptors;116 7.2.2.2;2.2.2 NOD like Receptors and RNA Helicases;117 7.2.2.3;2.2.3 Triggering Receptors Expressed on Myeloid Cells;118 7.2.2.4;2.2.4 Scavenger Receptors;119 7.2.3;2.3 Macrophage Antigen Complex-1 Receptor and Other Microglial Integrin-Associated Receptor Complexes;120 7.2.4;2.4 Reactive Oxygen Species;121 7.3;3 Adaptive Immunity in Multiple Sclerosis;123 7.3.1;3.1 Antigen Presentation and Immune Cell Invasion;123 7.3.2;3.2 Cytotoxic CD8 + T Cells;125 7.4;4 Conclusion;127 7.5;References;128 8;B Cells and Antibodies in MS;134 8.1;1 Introduction;134 8.2;2 The Role of CSF B Cells in CNS Inflammation;135 8.3;3 The Role of B Cells in CNS Pathology;137 8.4;4 The Role of B Cells in MS: Therapeutic Studies;139 8.5;5 Specificity of the Antibody Response in MS;140 8.5.1;5.1 Intrathecal IgG Production and Ocbs;140 8.5.2;5.2 OCB and EBV Antigens;141 8.5.3;5.3 Anti-Myelin Antibodies;141 8.5.4;5.4 Anti-aquaporin-4 Antibody