Immunogenomics and Human Disease

One of the major features that distinguishes vertebrates from invertebrates is the presence of a complex immune system. Over millions of years, many novel immune genes and gene families have emerged and their products form sophisticated pathways conferring protection against most pathogens. The Human Genome Project revealed that the immunoglobulin gene superfamily was one of the largest in the genome, containing more than 2% of all known human genes. High–throughput technologies for the study of DNA, mRNA and proteins, such as  microarrays and real–time gene amplification technologies, as well as biobank facilities, are enabling the investigation of these genes and pathways in ever more detail. The parallel development of databases and bioinformatics tools to store and interpret this information will also contribute to greater understanding of the function of the immune system.
Genomics is finally changing from an academic discipline to one with real clinical relevance. The study of immune regulation in response to pathogen invasion, to the presence of malignant or allogeneic tissue and, in some cases, to normal autologous tissue requires techniques that study the behaviour of whole systems in parallel. A genome–wide, systems biology approach is needed to understand the genetic and environmental factors that regulate the healthy immune system and its response to pathogens as well as to malignant cells arising within the body. It will also facilitate determining what goes wrong when the immune system attacks normal host cells, as in autoimmune diseases such as Type 1 diabetes.
Finally, greater knowledge of the immune system will enable us to use it to promote health and cure disease, through vaccine development – targeting both pathogens and tumour cells – and by manipulation of cellular and humoral defences.
This book provides an overview of key conceptual and molecular technologies being deployed in immunogenomics, follo wed by detailed evaluations of the impact of genomics and systems biology on important areas such as cancer immunology, autoimmunity, allergy and the response to infection. It will be of interest to all those working in immunology, as well as to bioinformaticians and specialists such as oncologists and microbiologists.

Spis treści:
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 t argets and small molecule drug candidates. Contribution to immunology (György Dormán, 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 (Sándor Pongor and András 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   S tudying 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 Rajnavölgyi).
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.