The immunome is the set of
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s and
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s that constitute the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
, excluding those that are widespread in other cell types, and not involved in the immune response itself.
It is further defined as the set of peptides derived from the
proteome
The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
that interact with the immune system.
There are numerous ongoing efforts to characterize and sequence the immunomes of
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
s,
mice, and elements of non-human primates. Typically, immunomes are studied using
immunofluorescence microscopy to determine the presence and activity of immune-related
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s and pathways.
Practical applications for studying the immunome include
vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. s, therapeutic proteins, and further treatment of other diseases.
The study of the immunome falls under the field of
immunomics
Immunomics is the study of immune system regulation and response to pathogens using genome-wide approaches. With the rise of genomic and proteomic technologies, scientists have been able to visualize biological networks and infer interrelationshi ...
.
Etymology
The word immunome is a
portmanteau
A portmanteau word, or portmanteau (, ) is a blend of words[immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...](_blank)
" and "
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
." See
omics
The branches of science known informally as omics are various disciplines in biology whose names end in the suffix '' -omics'', such as genomics, proteomics, metabolomics, metagenomics, phenomics and transcriptomics. Omics aims at the collect ...
for a further discussion.
Efforts to characterize
The exact size of the human immunome is currently unknown and has been a topic of study for decades. However, the amount of information it encodes is said to exceed the size of the human genome by several orders of magnitude due to, at least in part,
somatic hypermutation
Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM div ...
and
junctional diversity
Junctional diversity describes the DNA sequence variations introduced by the improper joining of gene segments during the process of V(D)J recombination. This process of V(D)J recombination has vital roles for the vertebrate immune system, as it ...
. There are several ongoing efforts to characterize the immunomes of humans and other species.
One major effort, launched in 2016, is a collaborative project between The Human Vaccines Project,
Vanderbilt University Medical Center
The Vanderbilt University Medical Center (VUMC) is a medical provider with multiple hospitals in Nashville, Tennessee, as well as clinics and facilities throughout Middle Tennessee. VUMC is an independent non-profit organization, but maintains acad ...
, and
Illumina, Inc. This project is entitled the Human Immunome Program and its goal is to decipher the complete collection of B and T immune cell receptors from the human population. Thousands of individuals will need to be studied in order to meet this goal, and they will need to represent different ages, genders, ethnicities, and geographical origins. Furthermore, people with diseases and people who have undergone vaccination will need to be studied as well.
The results of the program will be shared as an
open-sourced database
In computing, a database is an organized collection of data stored and accessed electronically. Small databases can be stored on a file system, while large databases are hosted on computer clusters or cloud storage. The design of databases s ...
. The sequencing project will continue until no new unique sequences occur within the B and T cell receptors and is expected to take ten years.
Similarly, there is a research project called the
Immunological Genome Project whose stated goal is to generate "a complete microarray dissection of gene expression and its regulation in the immune system of the mouse". In other words, the project is trying to define and characterize the immunome of the mouse. This project is primarily intended to function as a primary resource and the researchers actively accept suggestions from the community. The project team consists of more than 20 research labs, all working on various aspects of the project, including studying T cells, B cells, and
dendritic cells, along with many other types of cells within the mouse immunome. The project has been ongoing since 2008.
Efforts are also being made to characterize aspects of non-human immunomes, particularly non-human primates because of their genetic similarity to humans.
Methods of study
In order to gain useful knowledge about the immunome and its characteristics, the cells and components of the immune system must be phenotyped in a quick and pragmatic manner. There are hundreds of known cell types within the immune system and the possibility of detecting and characterizing them without the use of recent advances in immunophenotyping technology was remote because large amounts of an individual's blood would have been required. This outdated method is called low-dimensional immunophenotyping. However, high-dimensional immunophenotyping is now a possibility. The types of high-dimensional immunophenotyping can be broadly grouped into two categories: the use of
isotope
Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numb ...
s of
lanthanide and the use of
fluorophore
A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with se ...
s. These advanced technologies allow for up to 100 parameters to be measured at one time.
Applications
There are potentially far-reaching applications for studying the immunome. Dr. Anne De Groot believes that knowledge gained from the immunome could lead to discovering differences in the absolute number of T cell
epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...
s, and could reveal antigenic relationships between different but immunologically similar pathogens. She further states that there are possibilities for
autoimmune disease therapies and
organ transplantation
Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpor ...
.
Immunome investigation has proven useful in determining the symptoms and potential causes of
pulmonary fibrosis
Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...
on a molecular level.
The development of vaccines is also an application of immunome study as shown by Carlos F. Suárez and his colleagues. They were able to find components of a malaria vaccine that could be readily used in humans as a result of having characterized the cell surface receptor of an immune cell from an
owl monkey
Night monkeys, also known as owl monkeys or douroucoulis (), are nocturnal New World monkeys of the genus ''Aotus'', the only member of the family Aotidae (). The genus comprises eleven species which are found across Panama and much of South Ame ...
. These monkeys have been shown to be highly susceptible to human malaria, so they serve as a good model for the disease.
It could also be possible to develop an influenza vaccine that would provide protection from several strains of the virus.
Furthermore, analyzation of the immunomes of non-human primates and other species can reflect the evolutionary history of species as shown by David F. Plaza and his colleagues. This immunome data can also be helpful when testing antibody therapies on non-human primates to ensure they are safe for humans. This can be accomplished by being able to interpret results in the context of the slight differences in ortholog structure between the human and non-human primate immunomes.
Databases
There are a number of databases corresponding to the different facets of the human immunome and the immunomes of other species.
Immunome Knowledge Base (IKB)
An effort is being made to assemble immunological information into a singular database called the Immunome Knowledge Base(IKB). The two scientists behind the effort, Csaba Ortutay & Mauno Vihinen, have integrated data from three separate databases into IKB. These three databases, Immunome, ImmTree, and ImmunomeBase, all have separate, but related information pertaining to the immunome. Immunome contains entries to official gene names according to the
HUGO Gene Nomenclature Committee
The HUGO Gene Nomenclature Committee (HGNC) is a committee of the Human Genome Organisation (HUGO) that sets the standards for human gene nomenclature. The HGNC approves a ''unique'' and ''meaningful'' name for every known human gene, based on a ...
, alternative names, and locations of genes on the chromosomes. ImmTree contains entries related to the molecular evolution of the immune system, including orthologous genes and
phylogenetic trees. Finally, ImmunomeBase is a multi-species database related to immunity. Altogether, as of 2009, IKB has entries for more than 100,000 data items, including 893 entries for genes in the immunome.
Immune Epitope Database (IEDB)
This database serves as a resource for data on antibody and T cell epitopes studied in humans, non-human primates, and other species as it relates to disease, allergies, autoimmunity, and transplantation. The database also has tools to assist in the prediction and analysis of epitopes.
Immunome Database for Marsupials and Monotremes (IDMM)
This database has data for every known marsupial and monotreme immune gene. It serves as a resource for immunologists and researchers studying the evolution of mammalian immunity.
Immunology Database and Analysis Portal (ImmPort)
A database developed for the purpose of promoting the re-use of immunological data. It is a partnership between researchers at the University of California-San Francisco, Stanford University, the University of Buffalo, the Technion - Israel Institute of Technology, and Northrop Grumman. It encompasses results from over 400 studies related to immunology.
Immunological Genome Project (ImmGen)
This database is a public resource containing the data relating to the study of the immune system of the mouse.
Other databases
* Reference Database of Immune Cells (RefDIC)
* Innate Immune Database (IIDB)
* Immunogenetic Related Information Source (IRIS)
* DC ATLAS
References
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Systems biology