| Introduction |
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v | |
| Preface |
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vii | |
| Contributors |
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xi | |
| Part One The Cells Of The Pulmonary Immune Response |
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1 Overview of the Pulmonary Immune Response |
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1 | (18) |
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1 | (1) |
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II The Airways and the Mucociliary Apparatus |
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2 | (2) |
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III The Mucosa and Submucosa |
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4 | (3) |
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IV Immune Response in the Alveolar Spaces |
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7 | (5) |
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V Mast Cells and Basophils |
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12 | (1) |
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13 | (6) |
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2 Antigen-Presenting Cells |
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19 | (34) |
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19 | (1) |
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20 | (19) |
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39 | (3) |
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42 | (1) |
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42 | (11) |
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3 CD4 T Lymphocytes in Allergic Asthma |
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53 | (30) |
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53 | (1) |
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II A Historical Perspective of the CD4 T Cell in Asthma |
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54 | (1) |
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III Antigen Recognition by T Cells |
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55 | (1) |
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IV Effect of Allergen Dose and Genetic Background on the Development of T-Cell Responses |
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56 | (1) |
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V Effects of Affinity on the Development of T-Cell Responses |
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57 | (1) |
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VI Factors Influencing T-Helper-Cell Differentiation |
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58 | (1) |
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VII T-Cell Homing to the Lung |
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59 | (1) |
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VIII Th2 Cytokines in Asthma |
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60 | (3) |
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IX Exploring the Role of T Cells in Asthma Using Animal Models |
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63 | (2) |
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X Pharmacological Intervention as a Tool for Defining the Role of the T Cell in Asthma |
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65 | (1) |
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XI Induction of Isolated Late Asthmatic Reactions with Allergen Peptides |
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66 | (1) |
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XII MHC Restriction of Peptide-Induced LAR |
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67 | (1) |
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XIII Mechanisms Underlying Isolated LAR |
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68 | (1) |
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XIV T Cells as Mediators of Bronchial Hyperreactivity |
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69 | (4) |
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73 | (1) |
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73 | (10) |
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4 B-Cell Differentiation and IgE Synthesis |
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83 | (38) |
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83 | (6) |
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II Immunoglobulin Class Switching |
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89 | (11) |
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III Regulation of IgE Synthesis |
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100 | (2) |
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102 | (1) |
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103 | (5) |
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VI Conclusion and Prospects for the Near Future |
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108 | (1) |
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108 | (13) |
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5 Immune Functions of Mast Cells and Basophils |
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121 | (26) |
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121 | (1) |
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II Origin and Distribution of Mast Cells and Basophils |
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122 | (4) |
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III IgE Receptor Expression and Cellular Activation |
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126 | (1) |
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IV Mast Cell and Basophil Mediator Release |
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127 | (1) |
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V Specific Mediators of Mast Cells and Basophils |
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128 | (3) |
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VI Cellular Interactions of Mast Cells and Basophils |
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131 | (2) |
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VII Animal Models of Allergic Airways Disease |
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133 | (1) |
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VIII Lessons from Therapeutic Studies: Anti-IgE |
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134 | (1) |
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134 | (1) |
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135 | (12) |
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6 Immune Functions of Human Eosinophils |
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147 | (42) |
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147 | (1) |
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II Eosinophil Differentiation |
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148 | (7) |
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155 | (5) |
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160 | (3) |
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163 | (4) |
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VI Eosinophils in Allergic Disease |
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167 | (6) |
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VII Eosinophil-Mediated Inhibitory Mechanisms in Allergic Inflammation |
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173 | (1) |
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174 | (1) |
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174 | (15) |
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7 Immune Functions of Airway Epithelium |
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189 | (32) |
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189 | (1) |
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II Phagocytic Function of Airway Epithelial Cells |
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189 | (1) |
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III Epithelial Cells as Antigen-Presenting Cells |
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190 | (1) |
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IV Antimicrobial Activity of Airway Epithelial Cells |
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190 | (3) |
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V Epithelial Cells as Cellular Sources of Mediator Generation |
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193 | (8) |
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VI Epithelial Cells as Regulators of Airway Inflammation |
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201 | (2) |
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VII Anti-Inflammatory Role of Airway Epithelium |
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203 | (1) |
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VIII Role of Epithelial Cells in Asthma Pathogenesis |
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204 | (3) |
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IX Role of Epithelial Cells in Airway Remodeling |
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207 | (1) |
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208 | (13) |
| Part Two Regulatory Processes In The Pulmonary Immune Response |
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8 Tolerance to Inhaled Antigen |
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221 | (22) |
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I Asthma: An Inflammatory Response of the Airways to Inhaled Antigen |
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221 | (1) |
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II Disruption of Immunoregulation and Homeostasis Leads to Induction of Airway Inflammation |
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222 | (1) |
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III Mucosal Tissues of the Airways and Nasal Cavity |
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222 | (2) |
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IV In Vivo Models of Mucosal Tolerance |
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224 | (1) |
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V A Protective Role of IFN-y in Preventing Th2-Mediated Inflammatory Responses |
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224 | (1) |
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VI Immunoregulatory Role of y6+ T Cells in the Airway Mucosa |
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225 | (1) |
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VII Induction of Tolerance Following Mucosal Delivery of Antigen: the Role of Immunosuppressive Cytokines TGF-β and IL-10 in Suppressing Inflammatory Responses to Inhaled Antigens |
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226 | (2) |
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VIII Mechanisms Underlying Induction of Tolerance to Inhaled Antigen |
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228 | (3) |
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IX Role of Regulatory Cells and Linked Suppression in the Induction of Peripheral Tolerance |
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231 | (2) |
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233 | (1) |
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234 | (9) |
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9 Sensitization to Inhaled Allergen |
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243 | (18) |
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243 | (1) |
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II Immune Responses to Inhaled Allergens and Atopic Inflammation |
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243 | (1) |
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III Evolution of Allergen-Specific Immune Responses: Before Birth? |
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244 | (1) |
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IV Implications of Exposure to Antigens/Allergens In Utero |
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245 | (1) |
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V Maturation of Inhalant Allergen Response in the Postnatal Period |
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246 | (1) |
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VI Environmental Influences on Immune Development |
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247 | (4) |
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VII Identifying Children Who Will Ultimately Develop Persistent Inhalant Allergy |
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251 | (1) |
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VIII Interventions to Reduce Sensitization to Inhalants |
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251 | (2) |
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253 | (1) |
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253 | (8) |
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10 Polarization of T-Helper Cells |
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261 | (20) |
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261 | (1) |
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II Polarized Effector T Cells |
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262 | (2) |
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III Thl/Th2-Cell-Polarizing Molecules |
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264 | (2) |
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IV Intracellular Messengers of T-Cell Polarization |
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266 | (2) |
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268 | (1) |
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VI Polarized Effector Dendritic Cells |
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269 | (3) |
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VII Pattern Recognition Molecules |
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272 | (1) |
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VIII Alternative Pathways of T-Cell Polarization |
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273 | (1) |
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IX DC and Th2 Cells in Atopy |
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274 | (1) |
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275 | (1) |
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276 | (5) |
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11 CD28 and B7 Superfamily Members: Costimulation and Regulation of T-Cell Function |
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281 | (12) |
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Jose-Carlos Gutierrez-Ramos |
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I Contemporary Models of T-Cell Activation |
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281 | (1) |
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II CD28/B7 Costimulatory Pathway |
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282 | (2) |
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III The Expanding B7 Family |
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284 | (3) |
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IV Regulation of T-Cell Function by the B7 Family |
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287 | (1) |
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288 | (1) |
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288 | (5) |
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12 Control of Lymphocyte Trafficking Through the Lung |
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293 | (18) |
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293 | (1) |
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II Heterogeneity of Lymphoctye Subsets |
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294 | (1) |
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III Techniques for Studying Lymphocyte Traffic to the Lung |
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295 | (1) |
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IV Lymphocytes in the Lung Are Found in Different Comparments |
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295 | (2) |
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V Lymphocyte Numbers in the Lung Depend Not Only on Entry from the Blood |
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297 | (1) |
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VI The Unique Double Blood Supply of the Lung Is of Great Relevance to Lymphocyte Traffic |
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298 | (1) |
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VII Lack of a Bronchial Blood Supply in the Mouse |
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298 | (1) |
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VIII Lessons Learned from Neutrophil Migration to the Lung |
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298 | (1) |
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IX Defensins as Chemoattractants for Lymphoid Cells in the Lung |
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299 | (1) |
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X Postnatal Increase of Lymphocytes in the BAL Fluid |
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299 | (1) |
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XI Adhesion Molecules in Lymphocyte Traffic |
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300 | (3) |
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XII Chemokines in Lymphocyte Traffic to the Lung |
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303 | (1) |
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304 | (1) |
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304 | (7) |
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13 Neuroimmune Interactions in the Pathogenesis of Allergic Asthma |
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311 | (32) |
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I Cellular Immunity and Airway Inflammation in Allergic Asthma |
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311 | (1) |
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II Airway Hyperresponsiveness |
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312 | (1) |
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III Innervation of the Lung |
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313 | (6) |
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IV Neuronal Changes in Allergic Asthma |
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319 | (3) |
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V Effects of Inflammatory Mediators on Neurons |
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322 | (1) |
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VI Putative Role of Neurotrophins in the Pathogenesis of Asthma |
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323 | (3) |
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VII Effects of Neuropeptides on Immune Cells |
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326 | (3) |
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329 | (1) |
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330 | (13) |
| Part Three Integrated Immunology Of Airway Inflammation |
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14 Immunopathology of Atopic and Nonatopic Asthma |
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343 | (22) |
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343 | (1) |
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II Eosinophilic Airways Inflammation |
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344 | (2) |
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346 | (1) |
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347 | (5) |
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V Mast Cells and Basophils |
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352 | (1) |
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352 | (1) |
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VII Cytokines and Chemokines |
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353 | (6) |
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359 | (1) |
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359 | (6) |
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15 Immunology of Eosinophilic Airway Inflammation: What the Animal Models Teach Us |
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365 | (44) |
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I Human Asthma as a Th2-Driven Disorder? |
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365 | (3) |
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II Use of Murine Models of Eosinophilic Airway Inflammation |
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368 | (4) |
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III Role of Antigen-Presenting Cells in the Induction of Airway Eosinophilia in the Mouse |
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372 | (8) |
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IV Role of Antigen-Presenting Cells in the Maintenance of Airway Eosinophilia in Sensitized Animals |
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380 | (4) |
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V Role of CD4 Cells and Their Cytokine Products in Inducing Eosinophilic Airway Inflammation and Airway Hyperreactivity |
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384 | (6) |
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VI Role of CD8 Cells and Their Cytokine Products in Regulating Eosinophilic Airway Inflammation and Airway Hyperreactivity |
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390 | (1) |
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VII Do Mast Cells and IgE Have an Extended Role Beyond the Early Asthmatic Response by Orchestrating Airway Eosinophilia |
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391 | (1) |
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VIII Downstream Events That Contribute to the Asthmatic Phenotype in Mice |
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392 | (1) |
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393 | (1) |
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393 | (16) |
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16 Regulation of Cellular Traffic in the Asthmatic Lung |
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409 | (30) |
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Jose-Carlos Gutierrez-Ramos |
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409 | (1) |
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II Inflammatory Infiltrates |
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409 | (1) |
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III Leukocyte Recruitment |
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410 | (1) |
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410 | (2) |
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V The Chemokine Receptor Family |
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412 | (1) |
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413 | (4) |
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VII Evidence for the Functional Roles of Chemokines in Asthma |
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417 | (1) |
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VIII Migration of Antigen-Specific Effector T Cells |
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418 | (3) |
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IX Role of Chemokines in the Polarization of the Allergic Response |
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421 | (1) |
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X Coordination of Chemokine Responses |
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421 | (1) |
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XI Synergy with Other Inflammatory Mediators |
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422 | (1) |
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XII Chemotaxis Versus Chemokinesis |
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423 | (1) |
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XIII Regulation of Chemokine Responses |
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424 | (2) |
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XIV Chemokines and Their Receptors as Novel Therapeutic Agents |
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426 | (3) |
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429 | (1) |
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429 | (10) |
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17 Cytokine Regulation of Bronchial Hyperresponsiveness |
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439 | (28) |
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439 | (2) |
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441 | (8) |
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449 | (1) |
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IV Proinflammatory Cytokines |
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450 | (1) |
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V Immunomodulating Cytokines |
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451 | (3) |
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454 | (1) |
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454 | (13) |
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18 Immunological Functions of Inflammatory Mediators |
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467 | (62) |
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467 | (1) |
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468 | (2) |
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470 | (13) |
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483 | (10) |
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493 | (3) |
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496 | (1) |
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497 | (32) |
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19 Virally Induced Eosinophilic Airway Inflammation |
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529 | (14) |
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529 | (1) |
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II Respiratory Viral Infections |
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530 | (1) |
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III Vaccine-Enhanced RSV Disease in Humans |
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531 | (1) |
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IV Animal Models of RSV-Induced Eosinophilia |
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532 | (4) |
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V Modulating Lung Eosinophilia in Mice |
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536 | (1) |
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VI Role of Eosinophils in Viral Lung Disease |
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536 | (1) |
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537 | (1) |
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538 | (1) |
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538 | (5) |
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20 Airway Remodeling as the Outcome of a Chronic Immune Response to Inhaled Allergen |
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543 | (40) |
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543 | (1) |
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II Pathological Characteristics of Airway Remodeling |
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544 | (4) |
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III Airway Remodeling and Natural History of Asthma |
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548 | (1) |
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IV Cell Activation by Allergens and Possible Remodeling Effects |
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549 | (12) |
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V Airway Allergen Challenge Induces Airway Remodeling |
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561 | (3) |
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VI Longstanding Asthma and Chronic Inflammation Are Likely to Increase Airway Remodeling |
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564 | (1) |
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564 | (1) |
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565 | (18) |
| Part Four Immunological Aspects Of Asthma Therapy |
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21 Immunomodulatory Aspects of Current Asthma Therapy |
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583 | (20) |
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583 | (1) |
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II Current Asthma Therapy |
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583 | (2) |
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585 | (7) |
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592 | (1) |
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593 | (1) |
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594 | (1) |
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VII Steroid-Sparing Therapies |
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594 | (1) |
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VIII Specific Immunotherapy |
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595 | (1) |
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595 | (1) |
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595 | (8) |
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22 Immunomodulators in the Treatment of Asthma |
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603 | (16) |
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603 | (1) |
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604 | (1) |
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605 | (1) |
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IV Other Immunomodulators |
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606 | (3) |
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V The Future of Immunomodulators in the Treatment of Asthma |
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609 | (3) |
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VI T-Cell-Specific Immunosuppressive Drugs |
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612 | (1) |
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VII Targeting Cellular Recruitment |
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612 | (1) |
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VIII Antichemokine Strategies |
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612 | (1) |
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612 | (1) |
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613 | (6) |
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23 Immunotherapy of Asthma: Prospects for a Vaccine? |
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619 | (24) |
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619 | (2) |
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II Potential Use of Live or Killed Bacteria as an Asthma Vaccine |
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621 | (2) |
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III Development of an Asthma Vaccine Using CpG Oligodeoxynucleotides |
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623 | (5) |
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IV Plasmid DNA Immunization as a Basis for an Efficient Asthma Vaccine |
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628 | (2) |
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V Additional Approaches Leading to the Discovery of a Potential Asthma Vaccine |
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630 | (3) |
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633 | (2) |
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635 | (8) |
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24 Adenovirus-Mediated Gene Therapy for Asthma 643 Ryan E. Wiley, David Alvarez, and Manel Jordana |
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643 | (1) |
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II Prospects for Adenoviral Gene Therapy |
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644 | (8) |
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III Inherent Limitations of the Adenoviral Vector |
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652 | (5) |
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IV Therapeutic Gene Transfer: Targeting the Lung |
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657 | (3) |
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660 | (4) |
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664 | (13) |
| Author Index |
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677 | (106) |
| Subject Index |
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783 | |