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Clinical Applications of Immunomics

:	Vladimir Brusic, Andras Falus, Andras Falus
:	Andras Falus
:	Clinical Applications of Immunomics
:	Springer-Verlag
:	9780387792088
:	1
:	CHF 135.40
:

:	Nichtklinische Fächer
:	English

:	275
:	Wasserzeichen/DRM
:	PC/MAC/eReader/Tablet
:	PDF

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.

	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 Basop