Contents
Preface
List of contributors
1 Genotyping methods and disease gene identification
Ramón Kucharzak and Ivo Glynne Gut
1.1 Introduction
1.2 Genotyping of single-nucleotide polymorphisms
1.3 Methods for interrogating SNPs
1.4 Analysis formats
1.5 The current generation of methods for SNP genotyping
1.6 The next generation
1.7 Classical HLA typing
1.8 MHC haplotypes
1.9 Molecular haplotyping
1.10 Microhaplotyping
1.11 MHC and disease association
1.12 Conclusions
2 Glycomics and the Sugar Code: Primer to their Structural Basis and Functionality
Hans-Joachim Gabius
2.1 Introduction
2.2 Lectins as effectors in functional glycomics
2.3 Galectins: structural principles and intrafamily diversity
2.4 Ligand-dependent levels of affinity regulation
2.5 Perspectives for galectin-dependent medical applications
2.6 Conclusions
3 Proteomics in Clinical Research: Perspectives and Expectations
Ivan Lefkovits, Thomas Grussenmeyer, Peter Matt, Martin Grapow, Michael Lefkovits and Hans-Reinhard Zerkowski
3.1 Introduction
3.2 Proteomics: tools and projects
3.3 Discussion
3.4 Concluding remarks
4 Chemical genomics: bridging the gap between novel targets and small molecule drug candidates. Contribution to immunology
Gyrgy Dorm n, Takenori Tomohiro, Yasumaru Hatanaka and Ferenc Darvas
4.1 Introduction of chemical genomics: definitions
4.2 Chemical microarrays
4.3 Small molecule and peptide probes for studying binding interactions through creating a covalent bond
4.4 Photochemical proteomics
4.5 General aspects of photoaffinity labelling
4.6 Summary
5 Genomic and proteomic analysis of activated human monocytes
Ameesha Batheja, George Ho, Xiaoyao Xiao, Xiwei Wang and David Uhlinger
5.1 Primary human monocytes, as a model system
5.2 Transcriptional profiling of activated monocytes
5.3 Functional genomics
5.4 Proteomic analysis of activated human monocytes
6 Bioinformatics as a problem of knowlege representation: applications to some aspects of immunoregulation
S ndor Pongor and Andr s Falus
6.1 Introduction
6.2 Sequences and languages
6.3 Three-dimensional models
6.4 Genomes, proteomes, networks
6.5 Computational tools
6.6 Information processing in the immune system
6.7 Concluding remarks
7 Immune responsiveness of human tumours
Ena Wang and Francesco M. Marincola
7.1 Introduction
7.2 Defining tumour immune responsiveness
7.3 Studying immune responsiveness in human tumours
7.4 Immune responsiveness in the context of therapy
7.5 The spatial dimension in the quest for the target
7.6 Studying the receiving end - tumour as an elusive target for immune recognition
7.7 The role of the host in determining immune responsiveness
7.8 Concluding remarks
8 Chemokines regulate leukocyte trafficking and organ-specific metastasis
Andor Pivarcsi, Anja Mueller and Bernhard Homey
8.1 Chemokines and chemokine receptors
8.2 Chemokine receptors in the organ-specific recruitment of tumour cells
8.3 Cancer therapy using chemokine receptor inhibitors
8.4 Conclusions
9 Towards a unified approach to new target discovery in breast cancer: combining the power of genomics, proteomics and immunology
Laszlo G. Radvanyi, Bryan Hennessy, Kurt Gish, Gordon Mills and Neil Berinstein
9.1 Introduction
9.2 The use of CGH and DNA microarray-based transcriptional profiling for new target discovery in breast cancer
9.3 The challenge of new tumour marker/target validation: traditional techniques meet new proteomics tools
9.4 Immunological validation of new target genes in breast cancer: the emerging concept of the cancer 'immunome'
9.5 Future prospects: combining target discovery approaches in unified publicly accessible databases
10 Genomics and Functional Differences of Dendritic Cell Subsets
Peter Gogolak and Eva Rajnavlgyi
10.1 Introduction
10.2 Origin, differentiation and function of human dendritic cell subsets
10.3 Tissue localization of dendritic cell subsets
10.4 Antigen uptake by dentritic cells
10.5 Antigen processing and presentation by dendritic cells
10.6 Activation and polarization of dendritic cells
10.7 Enhancement of inflammatory responses by NK cells
10.8 Suppression of inflammatory responses by natural regulatory T cells
10.9 The role of dendritic cells and T-lymphocytes in tumour-specific immune responses
11 Systemic lupus erythematosus: new ideas for diagnosis and treatment
Sandeep Krishnan and George C. Tsokos
11.1 Introduction
11.2 Strategies for identifying diagnostic markers
11.3 Strategies for gene therapy for SLE
11.4 Conclusion and future direction
12 Immunogenetics of experimentally induced arthritis
Tibor T. Glant and Vyacheslav A. Adarichev
12.1 Rheumatoid arthritis in humans and murine proteoglycan-induced arthritis: introduction
12.2 Genetic linkage analysis of PGIA
12.3 Transcriptome picture of the disease: gene expression during initiation and progression of joint inflammation
12.4 Conclusions
13 Synovial activation in rheumatoid arthiritis
Lars C. Huber, Renate E. Gay and Steffen Gay
13.1 Introduction
13.2 Synovial activation in rheumatoid arthritis
13.3 Conclusions/perspectives
14 T cell epitope hierarchy in experimental autoimmune models
Edit Buzas
14.1 Introduction
14.2 Immunodominance and crypticity
14.3 Epitope spreading (endogenous self-priming)
14.4 Degenerate T cell epitope recognition
14.5 The self-reactive TCR repertoire
14.6 Thymic antigen presentation
14.7 Peripheral antigen presentation
14.8 Epitope hierarchy in experimental autoimmune encephalomyelitis
14.9 Epitope hierarchy in aggrecan-induced murine arthritis
14.10 Summary
15 Gene-gene interaction in immunology as exemplified by studies on autoantibodies against 60 kDa heat-shock protein
Zolt n Proh szka
15.1 Introduction
15.2 Basic features of gene-gene interactions
15.3 How to detect epistasis
15.4 Autoimmunity to heat-shock proteins
15.5 Epistatic effect in the regulation of anti-HSP6 autoantibody levels
15.6 Conclusions
16 Histamine genomics and metabolomics
Andras Falus, Hargita Hegyesi, Susan Darvas, Zoltan Pos and Peter Igaz
16.1 Introduction
16.2 Chemistry
16.3 Biosynthesis and biotransformation
16.4 Histidine decarboxylase gene and protein
16.5 Catabolic pathways of histamine
16.6 Histamine receptors
16.7 Histamine and cytokines, relation to the T cell polarization of the immune response
16.8 Histamine and tumour growth
16.9 Histamine research: an insight into metabolomics, lessons from HDC-deficient mice
16.10 Histamine genomics on databases
17 The histamine H4 receptor: drug discovery in the post-genomic era
Niall O'Donnell, Paul J. Dunford and Robin L. Thurmond
17.1 Introduction
17.2 Cloning of H3R and H4R
17.3 Generation of H4R-specific antagonists
17.4 High-throughput screening
17.5 Functional studies
17.6 Future prospects
18 Application of microarray technology to bronchial asthma
Kenji Izuhara, Kazuhiko Arima, Sachiko Kanaji, Kiyonari Masumoto and Taisuke Kanaji
18.1 Introduction
18.2 Lung tissue as 'source'
18.3 Particular cell as 'source'
18.4 Conclusions
19 Genomic investigation of asthma in human and animal models
Csaba Szalai
19.1 Introduction
19.2 Methods for localization of asthma susceptibility genes
19.3 Results of the association studies and genome-wide screens in humans
19.4 Animal models of asthma
19.5 Concluding remarks
20 Primary immunodeficiencies: genotype-phenotype correlations
Mauno Vihinen and Anne Durandy
20.1 Introduction
20.2 Immunodeficiency data services
20.3 Genotype-phenotype correlations
20.4 ADA deficiency
20.5 RAG1 and RAG2 deficiency
20.6 AID deficiency
20.7 WAS
20.8 XLA
20.9 Why GP correlations are not more common
21 Transcriptional profiling of dentritic cells in response to pathogens
Maria Foti, Francesca Granucci, Mattia Pelizzola, Norman Pavelka, Ottavio Beretta, Caterina Vizzardelli, Matteo Urbano, Ivan Zanoni, Giusy Capuano, Francesca Mingozzi and Paola Ricciardi-Castagnoli
21.1 Transcriptional profiling to study the complexity of the immune system
21.2 DC subsets and functional studies
21.3 DC at the intersection between innate and adaptive immunity
21.4 DC and infectious diseases
21.5 DC and bacteria interaction
21.6 DC and virus interaction
21.7 DC and parasite interaction
21.8 Leishmania mexicana molecular signature
21.9 Conclusions
22 Parallel biology: a systematic approach to drug target and biomarker discovery in chronic obstructive pulmonary disease
Laszlo Takacs
22.1 Introduction
22.2 Genome research is a specific application of parallel biology often regarded as systems biology
22.3 Chronic obstructive pulmonary disease
22.4 Goals of the study
22.5 Methods
22.6 Results
23 Mycobacterial granulomas: a genomic approach
Laura H. Hogan, Dominic O. Co and Matyas Sandor
23.1 Introduction
23.2 Initial infection of macrophage
23.3 Mycobacterial gene expression in the host
23.4 Host genes important to granuloma formation
23.5 Granulomatous inflammation as an ecological system
Index