Falus / Brusic Clinical Applications of Immunomics

1. Auflage 2008
ISBN: 978-0-387-79208-8
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 2, 275 Seiten

Reihe: Immunomics Reviews:

Innate immunity is one the most evolutionally conserved systems, designed to protect the organism from viruses and bacterial infections, stress and many other types of attacks from the outside world. During the past decade, the capacity of molecular biology and information technology to produce and analyse data have grown exponentially, rapidly reforming many aspects of immunology research in the post-genomics era. As a result, scientific understanding of signalling networks governing the innate immunity response in human tissues and other organisms has evolved beyond recognition, compared to even just a decade ago. Many strategies have been designed over the years to identify novel proteins, which have a crucial role in innate immunity responses by regulating particular signalling pathways. These projects had many advantages, including the definition of novel drug targets, as exemplified by the recent success of anti-TNF therapy, as well as leading to a better, system-wide understanding of the molecular control of innate immunity. In the past few years, a new concept, Immunomics, has been adopted to define an emerging, multidisciplinary field of research (Schonbach, 2003). Although rapid progress has been made to identify the proteins playing pivotal roles in the innate immunity-related signalling pathways (for example, TIR signalling pathways), the catalogue of proteins with a key regulatory function identified and studied is far from completed. Novel proteins need to be char- terised to gain a more comprehensive picture of how signalling networks are regulated.

Autoren/Hrsg.

Brusic, Vladimir

Falus, Andras

Inhaltsverzeichnis

1;Contents;6
2;Contributors;8
3;Introduction: Clinical Immunomics; A New Paradigm for Translational Research;12
3.1;References;17
4;Integrative Systems Approaches to Study Innate Immunity;18
4.1;1 Transcriptome Data Sets and the Macrophage Transcriptional Network;21
4.2;References;27
5;Immunomics: At the Forefront of Innate Immunity Research;31
5.1;1 Introduction;32
5.2;2 Cytokines;32
5.2.1;2.1 Interferons;32
5.2.2;2.2 Interleukins (ILs);33
5.2.2.1;2.2.1 Traditional IL-1 Cytokines;34
5.2.2.2;2.2.2 Novel IL-1 Cytokines;35
5.3;3 Cytokine Receptors;35
5.3.1;3.1 IL-1 Receptors;35
5.3.2;3.2 Toll-Like Receptors;36
5.3.2.1;3.2.1 Identification of Lps Locus;37
5.4;4 TIR Signalling Pathways (Downstream Components);39
5.4.1;4.1 MyD88;39
5.4.2;4.2 IRAKs;41
5.4.3;4.3 TRAFs;42
5.4.4;4.4 NF-kappaB/I-kappaBs;42
5.4.5;4.5 IKKs;43
5.5;5 Identification of Key Components of TIR Signalling;44
5.5.1;5.1 Methods for Identifying Novel Components of Signalling Pathway;44
5.5.2;5.2 cDNA Library Screening as a Powerful Tool to Explore Signalling Networks;44
5.6;6 Concluding Remarks;47
5.7;References;48
6;Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety;55
6.1;1 Introduction;55
6.2;2 Defining the Immunome;56
6.2.1;2.1 How Large Is the Immunome?;57
6.3;3 Steps in the Development of an Epitope-Based IDV;57
6.3.1;3.1 Select Protein Antigens of Interest;57
6.3.2;3.2 Identifying B Cell Antigens;59
6.3.3;3.3 Identifying T Cell Antigens;59
6.3.3.1;3.3.1 In Vitro Assays: Peptide Binding Assays;60
6.3.3.2;3.3.2 In Vitro Assays: Measuring T Cell Responses;60
6.3.4;3.4 Select Delivery Vehicle and Adjuvant;61
6.3.5;3.5 Animal Model for Vaccine Efficacy;62
6.3.6;3.6 Challenge Studies;63
6.3.7;3.7 Clinical Development;63
6.4;4 Epitope Mapping Tools for IDV;64
6.4.1;4.1 EpiMatrix: T cell Epitope Mapping for IDV;64
6.4.2;4.2 ClustiMer: Finding Promiscuous T cell Epitopes;65
6.5;5 Additional Vaccine Design Tools;66
6.5.1;5.1 Conservatrix: Finding Conserved T Cell Epitopes;66
6.5.2;5.2 EpiAssembler: Immunogenic Consensus Sequence Epitopes;67
6.5.3;5.3 Eliminating Cross-Reactivity (BlastiMer);68
6.5.4;5.4 Vaccine CAD: Aligning Epitopes;69
6.5.5;5.5 HLA Coverage for IDV;70
6.5.6;5.6 Aggregatrix: Aggregation of Epitopes into the Ideal IDV;70
6.5.7;5.7 Individualized T Cell Epitope Measure (iTEM);72
6.5.8;5.8 Anticipating Processing and Presentation;72
6.6;6 Methods of Confirming IDV;73
6.6.1;6.1 Two Case Studies;73
6.6.1.1;6.1.1 Bacterial (Tularemia);73
6.6.1.2;6.1.2 Therapeutic HPV Vaccine;74
6.7;7 Advantages and Disadvantages of IDV;75
6.8;8 Future Research;76
6.9;9 Conclusion;77
6.10;References;78
7;Immunodeficiencies and Immunome: Diseases and Information Services;86
7.1;1 ImmunoDeficiency Resource (IDR);90
7.2;2 Immunodeficiency Diagnostics Registry (IDdiagnostics);91
7.3;3 PIDexpert;92
7.4;4 Immunodeficiency Mutation Databases, IDbases;93
7.4.1;4.1 Using the IDbases;95
7.5;5 Genotype- Phenotype Correlations;95
7.6;6 Immunome;96
7.7;References;98
8;Immunomics of Immune Rejection;101
8.1;1 Introduction;102
8.2;2 Relevance of Tumor-Specific Immune Responses in Humans;102
8.3;3 Genetic Variables that May Affect the Ability of the Host to Control Cancer Growth;104
8.4;4 Cancer Cell Biology as the Orchestrator of the Host Immune Response;105
8.5;5 The Study of the Requirements for Immune Rejection Within the Target Organ;109
8.6;References;112
9;Spectrum, Function, and Value of Targets Expressed in Neoplastic Mast Cells;120
9.1;1 Pathogenesis of Mastocytosis and Classification;120
9.2;2 Current treatment options for patients with systemic mastocytosis;122
9.3;3 Expression of Molecular Targets on the Surface of Neoplastic Cells;123
9.4;4 Signal Transduction-Associated Targets in Neoplastic Mast Cells;126
9.5;5 Molecular Targets that Play a Role in Growth or Survival of Mast Cells;128
9.6;6 Mast Cell-Derived Effector Molecules as Targets of Therapy;129
9.7;7 Targeting of Mast Cell Progenitors and Neoplastic Stem Cells in Mastocytosis;130
9.8;8 Concluding Remarks;131
9.9;References;131
10;Structure, Allergenicity, and Cross-Reactivity of Plant Allergens;139
10.1;1 Introduction;139
10.2;2 Protein Families of Plant Allergens;140
10.2.1;2.1 The Prolamin Superfamily;142
10.2.2;2.2 Profilins;145
10.2.3;2.3 Bet v 1-Related Allergens;146
10.2.4;2.4 Seed Storage Globulins;147
10.2.5;2.5 Expansins and Expansin-Related Allergens;148
10.2.6;2.6 Polcalcins;149
10.3;3 Common Molecular Properties of Allergens;150
10.3.1;3.1 Properties of Food Allergens;151
10.3.2;3.2 Properties of Pollen Allergens;152
10.4;4 Sequences, Structures, and Cross-Reactivity;153
10.5;5 Protein Family Membership and Prediction of Allergenicity;154
10.6;6 Concluding Remarks;155
10.7;References;156
11;The Live Basophil Allergen Array (LBAA): A Pilot Study;164
11.1;1 Live Basophil Allergen Array;164
11.2;2 A Short History of Tests for Allergy;165
11.2.1;2.1 Skin Prick Tests and Specific IgE Determination;165
11.2.2;2.2 Basophil Activation Tests;166
11.2.3;2.3 Allergen Microarray Tests: The Next Generation?;167
11.3;3 Immunobiology of IgE-Dependent Basophil Activation;168
11.3.1;3.1 The High-Affinity IgE Receptor FcepsivRI;168
11.3.2;3.2 Lipid Rafts and Basophil Activation;169
11.4;4 Basophil Binding and Monitoring of Activation;170
11.4.1;4.1 Basophil Binding in the LBAA;170
11.4.2;4.2 Detection of Basophil Activation;173
11.5;5 Potential Pitfalls of the LBAA;175
11.6;6 Conclusion;177
11.7;References;178
12;Emerging Therapies for the Treatment of Autoimmune Myasthenia Gravis;181
12.1;1 Introduction;182
12.1.1;1.1 Clinical Features;183
12.2;2 Current Treatments and Treatments at the Clinical Trial Stage;184
12.2.1;2.1 Anticholinesterase Drugs;184
12.2.2;2.2 Other Symptomatic Treatments;185
12.2.3;2.3 Thymectomy;186
12.2.4;2.4 Oral Corticosteroids;186
12.2.5;2.5 Non-Steroidal Immunosuppressants;186
12.2.6;2.6 Plasmapheresis;188
12.2.7;2.7 Immunoadsorption;190
12.2.8;2.8 Intravenous Immunoglobulin (IVIg);191
12.3;3 Emerging theRapies;192
12.3.1;3.1 Immune System Ablation;193
12.3.2;3.2 Gene Therapy;193
12.3.3;3.3 Phosphodiesterase Inhibitors;194
12.3.4;3.4 Suppression of MG by Mucosally Administered Recombinant AChR Fragments;195
12.3.5;3.5 Manipulated Antigen-Presenting Cells (APCs);196
12.3.6;3.6 Altered Peptide Ligands (APLs);197
12.3.7;3.7 Protective anti-AChR Antibody Fragments;198
12.3.8;3.8 Anti-TCR Antibodies;200
12.3.9;3.9 RNA Aptamers;201
12.3.10;3.10 Anti-AChR Ab-Specific Plasma Clearance;201
12.4;4 Future Perspective;204
12.5;References;205
13;New Diagnostic and Therapeutic Options for the Treatment of Multiple Sclerosis;215
13.1;1 Introduction;216
13.2;2 Targeting Blood-Brain Barrier Inflamed Sites by Cationic Colloidal Carriers;217
13.3;3 The Role of MMPs in MS Pathogenesis and the Modulation of Their Expression and Activity for MS Treatment;220
13.4;4 The Relevance of Nutrition in the Course of MS;223
13.4.1;4.1 Background;223
13.4.2;4.2 Diet and MS;224
13.4.2.1;4.2.1 The Role of Animal Fat;224
13.4.2.2;4.2.2 Milk and MS;224
13.4.2.2.1;4.2.2.1 Milk MFGM Proteins and Multiple Sclerosis;225
13.4.2.2.2;4.2.2.2 Concluding Remarks on Milk and MS;226
13.4.3;4.3 Gut, Food Absorption, and MS;226
13.4.3.1;4.3.1 Dietary Remarks on Gut and Malabsorption;227
13.4.4;4.4 Oxidative Stress and Dietary Antioxidants;227
13.4.4.1;4.4.1 Unsaturated Fatty Acids from Vegetables;229
13.4.4.2;4.4.2 PUFA from Sea Food and MS;229
13.4.4.3;4.4.3 The Role of Insulin in MS;230
13.5;5 Conclusions;230
13.6;References;230
14;Glycoimmunomics of Human Cancer: Relevance to Monitoring Biomarkers of Early Detection and Therapeutic Response;237
14.1;1 Introduction;238
14.2;2 Diversity of Glycoantigens;238
14.3;3 Gangliosides;239
14.3.1;3.1 Family of Glycoantigens;239
14.3.2;3.2 Origin and Distribution During Tumor Formation;240
14.3.3;3.3 Antigenic Determinants;242
14.4;4 Glycoimmunomics of Gangliosides;243
14.4.1;4.1 Gangliosides Are T-Independent Antigens;244
14.4.2;4.2 Gangliosides Elicit IgM Response in Humans;244
14.4.3;4.3 Gangliosides Suppress Immune Functions;246
14.4.4;4.4 Cell Recognition of Gangliosides;248
14.4.5;4.5 Emerging Concepts of Clinical Glycoimmunomics of Human Cancer;250
14.5;5 Glycoimmunomic Biomarkers;251
14.5.1;5.1 Glycoimmunomic Biomarker: Origin of the Hypothesis;251
14.5.2;5.2 Glycoimmunomic Early Biomarker of Prostate Cancer;252
14.5.3;5.3 Glycomic Therapeutic Response Biomarker for Human Melanoma;254
14.6;6 Conclusions;256
14.7;References;258
15;Translational Immunomics of Cancer Immunoprevention;263
15.1;1 Cancer Immunoprevention;263
15.2;2 Immunoprevention of Viral Tumors;264
15.3;3 Immunoprevention of Non-viral Tumors;264
15.3.1;3.1 HER-2/neu Transgenic Mice;265
15.3.2;3.2 Mammary Carcinoma Immunoprevention in HER-2/neu Transgenic Mice;266
15.4;4 Transcriptomics of HER-2/neu Mammary Carcinoma Development and Immunoprevention;267
15.5;5 Oncoantigens;268
15.6;6 Mining for New Oncoantigens;269
15.7;7 Translational Development of Cancer Immunoprevention;270
15.8;8 Mathematical Models of Cancer Immunoprevention;270
15.9;9 Toward Clinical Implementation, or Back to Immunotherapy;275
15.10;References;276
16;Index;279