Clinical Applications of Immunomics (eBook)

Contents 6
Contributors 8
Introduction: Clinical Immunomics A New Paradigm for Translational Research
References 17
Integrative Systems Approaches to Study Innate Immunity 18
1 Transcriptome Data Sets and the Macrophage Transcriptional Network 21
References 27
Immunomics: At the Forefront of Innate Immunity Research 31
1 Introduction 32
2 Cytokines 32
2.1 Interferons 32
2.2 Interleukins (ILs) 33
2.2.1 Traditional IL-1 Cytokines 34
2.2.2 Novel IL-1 Cytokines 35
3 Cytokine Receptors 35
3.1 IL-1 Receptors 35
3.2 Toll-Like Receptors 36
3.2.1 Identification of Lps Locus 37
4 TIR Signalling Pathways (Downstream Components) 39
4.1 MyD88 39
4.2 IRAKs 41
4.3 TRAFs 42
4.4 NF-kappaB/I-kappaBs 42
4.5 IKKs 43
5 Identification of Key Components of TIR Signalling 44
5.1 Methods for Identifying Novel Components of Signalling Pathway 44
5.2 cDNA Library Screening as a Powerful Tool to Explore Signalling Networks 44
6 Concluding Remarks 47
References 48
Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety 55
1 Introduction 55
2 Defining the Immunome 56
2.1 How Large Is the Immunome? 57
3 Steps in the Development of an Epitope-Based IDV 57
3.1 Select Protein Antigens of Interest 57
3.2 Identifying B Cell Antigens 59
3.3 Identifying T Cell Antigens 59
3.3.1 In Vitro Assays: Peptide Binding Assays 60
3.3.2 In Vitro Assays: Measuring T Cell Responses 60
3.4 Select Delivery Vehicle and Adjuvant 61
3.5 Animal Model for Vaccine Efficacy 62
3.6 Challenge Studies 63
3.7 Clinical Development 63
4 Epitope Mapping Tools for IDV 64
4.1 EpiMatrix: T cell Epitope Mapping for IDV 64
4.2 ClustiMer: Finding Promiscuous T cell Epitopes 65
5 Additional Vaccine Design Tools 66
5.1 Conservatrix: Finding Conserved T Cell Epitopes 66
5.2 EpiAssembler: Immunogenic Consensus Sequence Epitopes 67
5.3 Eliminating Cross-Reactivity (BlastiMer) 68
5.4 Vaccine CAD: Aligning Epitopes 69
5.5 HLA Coverage for IDV 70
5.6 Aggregatrix: Aggregation of Epitopes into the Ideal IDV 70
5.7 Individualized T Cell Epitope Measure (iTEM) 72
5.8 Anticipating Processing and Presentation 72
6 Methods of Confirming IDV 73
6.1 Two Case Studies 73
6.1.1 Bacterial (Tularemia) 73
6.1.2 Therapeutic HPV Vaccine 74
7 Advantages and Disadvantages of IDV 75
8 Future Research 76
9 Conclusion 77
References 78
Immunodeficiencies and Immunome: Diseases and Information Services 86
1 ImmunoDeficiency Resource (IDR) 90
2 Immunodeficiency Diagnostics Registry (IDdiagnostics) 91
3 PIDexpert 92
4 Immunodeficiency Mutation Databases, IDbases 93
4.1 Using the IDbases 95
5 Genotype- Phenotype Correlations 95
6 Immunome 96
References 98
Immunomics of Immune Rejection 101
1 Introduction 102
2 Relevance of Tumor-Specific Immune Responses in Humans 102
3 Genetic Variables that May Affect the Ability of the Host to Control Cancer Growth 104
4 Cancer Cell Biology as the Orchestrator of the Host Immune Response 105
5 The Study of the Requirements for Immune Rejection Within the Target Organ 109
References 112
Spectrum, Function, and Value of Targets Expressed in Neoplastic Mast Cells 120
1 Pathogenesis of Mastocytosis and Classification 120
2 Current treatment options for patients with systemic mastocytosis 122
3 Expression of Molecular Targets on the Surface of Neoplastic Cells 123
4 Signal Transduction-Associated Targets in Neoplastic Mast Cells 126
5 Molecular Targets that Play a Role in Growth or Survival of Mast Cells 128
6 Mast Cell-Derived Effector Molecules as Targets of Therapy 129
7 Targeting of Mast Cell Progenitors and Neoplastic Stem Cells in Mastocytosis 130
8 Concluding Remarks 131
References 131
Structure, Allergenicity, and Cross-Reactivity of Plant Allergens 139
1 Introduction 139
2 Protein Families of Plant Allergens 140
2.1 The Prolamin Superfamily 142
2.2 Profilins 145
2.3 Bet v 1-Related Allergens 146
2.4 Seed Storage Globulins 147
2.5 Expansins and Expansin-Related Allergens 148
2.6 Polcalcins 149
3 Common Molecular Properties of Allergens 150
3.1 Properties of Food Allergens 151
3.2 Properties of Pollen Allergens 152
4 Sequences, Structures, and Cross-Reactivity 153
5 Protein Family Membership and Prediction of Allergenicity 154
6 Concluding Remarks 155
References 156
The Live Basophil Allergen Array (LBAA): A Pilot Study 164
1 Live Basophil Allergen Array 164
2 A Short History of Tests for Allergy 165
2.1 Skin Prick Tests and Specific IgE Determination 165
2.2 Basophil Activation Tests 166
2.3 Allergen Microarray Tests: The Next Generation? 167
3 Immunobiology of IgE-Dependent Basophil Activation 168
3.1 The High-Affinity IgE Receptor FcepsivRI 168
3.2 Lipid Rafts and Basophil Activation 169
4 Basophil Binding and Monitoring of Activation 170
4.1 Basophil Binding in the LBAA 170
4.2 Detection of Basophil Activation 173
5 Potential Pitfalls of the LBAA 175
6 Conclusion 177
References 178
Emerging Therapies for the Treatment of Autoimmune Myasthenia Gravis 181
1 Introduction 182
1.1 Clinical Features 183
2 Current Treatments and Treatments at the Clinical Trial Stage 184
2.1 Anticholinesterase Drugs 184
2.2 Other Symptomatic Treatments 185
2.3 Thymectomy 186
2.4 Oral Corticosteroids 186
2.5 Non-Steroidal Immunosuppressants 186
2.6 Plasmapheresis 188
2.7 Immunoadsorption 190
2.8 Intravenous Immunoglobulin (IVIg) 191
3 Emerging theRapies 192
3.1 Immune System Ablation 193
3.2 Gene Therapy 193
3.3 Phosphodiesterase Inhibitors 194
3.4 Suppression of MG by Mucosally Administered Recombinant AChR Fragments 195
3.5 Manipulated Antigen-Presenting Cells (APCs) 196
3.6 Altered Peptide Ligands (APLs) 197
3.7 Protective anti-AChR Antibody Fragments 198
3.8 Anti-TCR Antibodies 200
3.9 RNA Aptamers 201
3.10 Anti-AChR Ab-Specific Plasma Clearance 201
4 Future Perspective 204
References 205
New Diagnostic and Therapeutic Options for the Treatment of Multiple Sclerosis 215
1 Introduction 216
2 Targeting Blood-Brain Barrier Inflamed Sites by Cationic Colloidal Carriers 217
3 The Role of MMPs in MS Pathogenesis and the Modulation of Their Expression and Activity for MS Treatment 220
4 The Relevance of Nutrition in the Course of MS 223
4.1 Background 223
4.2 Diet and MS 224
4.2.1 The Role of Animal Fat 224
4.2.2 Milk and MS 224
4.2.2.1 Milk MFGM Proteins and Multiple Sclerosis 225
4.2.2.2 Concluding Remarks on Milk and MS 226
4.3 Gut, Food Absorption, and MS 226
4.3.1 Dietary Remarks on Gut and Malabsorption 227
4.4 Oxidative Stress and Dietary Antioxidants 227
4.4.1 Unsaturated Fatty Acids from Vegetables 229
4.4.2 PUFA from Sea Food and MS 229
4.4.3 The Role of Insulin in MS 230
5 Conclusions 230
References 230
Glycoimmunomics of Human Cancer: Relevance to Monitoring Biomarkers of Early Detection and Therapeutic Response 237
1 Introduction 238
2 Diversity of Glycoantigens 238
3 Gangliosides 239
3.1 Family of Glycoantigens 239
3.2 Origin and Distribution During Tumor Formation 240
3.3 Antigenic Determinants 242
4 Glycoimmunomics of Gangliosides 243
4.1 Gangliosides Are T-Independent Antigens 244
4.2 Gangliosides Elicit IgM Response in Humans 244
4.3 Gangliosides Suppress Immune Functions 246
4.4 Cell Recognition of Gangliosides 248
4.5 Emerging Concepts of Clinical Glycoimmunomics of Human Cancer 250
5 Glycoimmunomic Biomarkers 251
5.1 Glycoimmunomic Biomarker: Origin of the Hypothesis 251
5.2 Glycoimmunomic Early Biomarker of Prostate Cancer 252
5.3 Glycomic Therapeutic Response Biomarker for Human Melanoma 254
6 Conclusions 256
References 258
Translational Immunomics of Cancer Immunoprevention 263
1 Cancer Immunoprevention 263
2 Immunoprevention of Viral Tumors 264
3 Immunoprevention of Non-viral Tumors 264
3.1 HER-2/neu Transgenic Mice 265
3.2 Mammary Carcinoma Immunoprevention in HER-2/neu Transgenic Mice 266
4 Transcriptomics of HER-2/neu Mammary Carcinoma Development and Immunoprevention 267
5 Oncoantigens 268
6 Mining for New Oncoantigens 269
7 Translational Development of Cancer Immunoprevention 270
8 Mathematical Models of Cancer Immunoprevention 270
9 Toward Clinical Implementation, or Back to Immunotherapy 275
References 276
Index 279