Immunomics
Therefore, it is critical that the expression patterns of these immune cell types be deciphered in the context of a network, and not as an individual, so that their roles be correctly characterized and related to one another.
[1] Defects of the immune system such as autoimmune diseases, immunodeficiency, and malignancies can benefit from genomic insights on pathological processes.
These classical approaches could only visualize this system as a static condition and required a large amount of time and labor.
It has revealed that some of the immune system's most distinguishing features are the continuous motility, turnover, and plasticity of its constituent cells.
New, proteomic approaches, including T-cell and B-cells-epitope mapping, can also accelerate the pace at which scientists discover antibody-antigen relationships.
A host's immune system responds to pathogen invasion by a set of pathogen-specific responses in which many “players” participate; these include antibodies, T-helper cells, cytotoxic T-cells, and many others.
The ‘immunome’ of a pathogen is described by its set of epitopes, and can be defined by comparing genome sequences and applying immunoinformatic tools.
[3] Ash Alizadeh et al. were some of the first to recognize the potential of cDNA microarrays to define gene expression of immune cells.
Their analysis probed gene expression of human B and T lymphocytes during cellular activation and/or stimulation with cytokines, a type of signaling regulatory molecule.
In the concluding paragraphs of their landmark paper, these scientists state “virtually every corner of immunological research will benefit from cDNA microarray analysis of gene expression,” and, thus, heralded the rise of immunomics.
These can be used for functional immunomic applications to the understanding of autoimmune diseases and allergies, definition of B-cell epitopes, vaccine studies, detection assays, and analysis of antibody specificity.
MHC microarrays are the most recent development in immunomic arrays and use peptide-MHC complexes and their co-stimulatory molecules as probes and T-cell populations as targets.
[7] The Lymphochip is a specialized human cDNA microarray enriched for genes related to immune function and created by Ash Alizadeh at Stanford University.
Finally, 3,183 genes that are known or suspected to have roles in immune function, oncogenesis, apoptosis, cell proliferation, or being open reading frames from pathogenic human viruses were used on the Lymphochip.
Immunomics harnesses the power of bioinformatics and offers mapping algorithms that accelerate the discovery of epitope sequences.
These algorithms are relevant to vaccine design and for characterizing and modifying immune responses in the context of autoimmunity, endocrinology, allergy, transplantation, diagnostics and engineering of therapeutic proteins.
Whereas the following list of contributions is not complete, it is meant to demonstrate the broad application of immunomic research and powerful consequences on immunology.
Early activated DCs are enabled to migrate from non-lymphoid tissues to lymph nodes, where they can prime T-cell responses.
For example, the transcriptional profiles from thymic medullary epithelial immune cells mapped closer to lymphocytes than to other epithelia.
Additionally, it may better explain the observed plasticity in lymphoid and myeloid cell differentiation because of the considerable overlap between global expression profiles of these different lineages.
[14] Networks represent the broadest level of genetic interactions and aim to link all genes and transcripts in the immunological genome.
This analysis suggests a hierarchical network where a small number of highly connected genes (called “hubs”) regulated most interactions.
Notably, MYC was found to directly control BYSL, a highly conserved, but poorly characterized gene, and is the largest hub in the whole B cell network.
Changes gene expression signatures may precede clinical exacerbation of symptoms, like in multiple sclerosis, and allow physicians to nip these “flare-ups” in the bud.
The Immunological Genome Project seeks to generate a complete compendium of protein-coding gene expression for all cell populations in the mouse immune system.
