A free-source in silico genetics-based model of the immune system: How does the Immune System recognize the individuality of a specific Invader? How does it discriminate Invader from Constituent? How does it translate the recognition of an Antigen into a destroying reaction? How does it learn, in order to repel a second attack much faster than the first? How does the Immune System fail in the above?

The initial application will be multiple sclerosis research. "Plug-ins" will model other human diseases and even veterinary applications. This project may also provide insight into network security.

Pandora: Project Dictionary

Name	Kind	Description
Immune System	system	a vertebrate's elaborate subsystem of protective measures that work by a learning process
Immunology	term	the study of the Immune System
Constituent	class	anything natural/normal to the body
Invader	class	anything foreign/abnormal to the body
Antigen	class	an Invader (or a Constituent, incorrectly) which is recognized by -- or triggers the formation of -- an Antibody or Lymphocyte
recognizes	relationship	the Immune System recognizes the presence of Antigens
discriminates	relationship	the Immune System tries to discriminate between an Invader and a Constituent
destroys	relationship	the Immune System destroys Antigens
Immunopathology	term	the study of diseases due to a damaged Immune System (lupus, multiple sclerosis, rheumatoid arthritis, AIDS)
Autoimmune Disease	state	when the Immune System does not discriminate correctly

The Lymphocytes of the Immune System respond to Antigens in three different ways (system operations):

Name	Kind	Description
Humoral Immunity	system operation	certain Proteins (Immunoglobulin and Complements) in the body's bloodstream carry out the immune response; Antibody Diversity and Clonal Selection are key parts
Protein	class	a large polymer composed of more than 50 Amino Acids
Complement	class	an immune Protein which destroys Bacteria to which Antibody is bound
B Lymphocyte	class	Lymphocyte with Antibodies on its Surface; when these bind, the cell becomes a plasma cell and secretes Antibodies into the bloodstream
Surface	class	every cell has a Surface
Antibody Diversity	concept	routinely, bone marrow produces an enormous number of B Lymphocytes, each with structurally different Antibody regions but lasting only a few days
Memory B Cell	class	long-lived descendant of a stimulated B Lymphocyte, in case of a secondary immune response
Clonal Selection	concept	When a vertebrate encounters an Antigen, the Antigen is bound only by those B Lymphocytes with the appropriate Antibodies on their Surface. These selected B Lymphocytes multiply/clone and secrete the specific Antibodies.

An Antibody is a Y-shaped molecule composed of 2 matched pairs of Protein Chains. It has 2 Binding Domains and 1 Effector Domain. There are 5 major classes of Immunoglobulin (blood Protein) Antibody. All are made by B Lymphocytes.

Name	Kind	Description
Domain	term	Protein region with distinct structure and activity
Binding Domain	class	region of Antibody which tries to bind with Antigen; highly specific to a particular Antibody
Effector Domain	class	region of Antibody which signals the initiation of processes to rid the body of the bound Antibody-Antigen (e.g, phagocytosis); also provides Signals which distribute Antibodies to various bodily fluids
signals	relationship	communicates via molecular circuitry
IgM	class	pentamer Immunoglobulin Antibody; five Antibody molecules polymerize in a cluster; stimulates Complements and Macrophages
IgG	class	monomer; main serum Antibody; stimulates Complements and Macrophages
IgA	class	trimer, dimer, and monomer forms; in saliva, tears, lungs, intestines; defends against Microorganisms
IgE	class	monomer; mainly in tissues as a defense against parasites, but also stimulates the release of histamine, causing allergic reaction
IgD	class	monomer; no known function
H Chain	class	heavy Protein of namesake Immunoglobulin: Mu, Gamma, Alpha, Epsilon, Delta respectively
L Chain	class	light Protein of Immunoglobulin: Kappa or Lambda

The introduction of genetics becomes necessary.

Name	Kind	Description
Chromosome	class	unit of a cell's genetic material (DNA and special Proteins); paired Chromosomes have paired Alleles (variations on a Gene); human cells have 23 pairs
Chromosome 14	class	has Gene for H Chains
Chromosome 2	class	has Gene for Kappa L Chains
Chromosome 22	class	has Gene for Lambda L Chains
Gene	class	DNA sequence(s) necessary for creating a particular Protein or RNA molecule
DNA	class	lifeless strand of genetic sequences; nucleic acid polymerized from deoxyribose nucleotides of Adenine, Cytosine, Guanine, and Thymine
RNA	class	nucleic acid which retrieves and converts genetic information into Protein or more RNA; polymerized from ribose nucleotides of Adenine, Cytosine, Guanine, and Uracil
Codon	class	a sequence of three nucleotides whose 4x4x4 permutations redundantly specify the 20 Amino Acids as well as START and STOP

How does the Immune System generate Antibody Diversity from only three Genes? By shuffling each Gene like a deck of cards. That is, Recombinant DNA concepts link Antibody Proteins and Genes.

Name	Kind	Description
mRNA Synthesis	factory	Transcription: an enzyme copies Gene's DNA as RNA; then RNA Processing: caps ends and removes Introns
Template	class	original strand of DNA copied as RNA or DNA
snRNP	class	small nuclear ribonucleoprotein particle; consists of snRNA and several Proteins; assists in splicing during mRNA Processing
Protein Synthesis	factory	Translation: three types of RNA create a Protein (e.g, an Antibody)
mRNA	class	messenger RNA's sequence of Codons specifies a sequence of Amino Acids
tRNA	term	transfer RNA creates a Protein one mRNA-specified Amino Acid at a time
rRNA	term	ribosomal RNA forms the Ribosome where the Protein is created

Several genetic sequences encode information in the form of Active RNA (instead of Protein). These useful byproducts are erroneously referred to as junk:

Name	Kind	Description
Antisense RNA	class	created from the DNA strand complementary to the strand of a Protein-coding Gene; can bind to the Gene's mRNA, thereby blocking Synthesis
Intron	class	RNA sequence within the RNA Transcript of a Protein-coding Gene which does not code for Protein; instead, may be active as microRNA which can effectively suppress other Genes
RNA Interference	system operation	double-stranded RNA (of a Virus, bound Antisense RNA, or microRNA) within a Cell is peeled apart by Enzymes, which then use the RNA fragments to destroy complementary RNA
Riboswitch	class	RNA (from the non-coding DNA between Protein-coding Genes) which acts as a switch: its Protein-coding sequence activates (changes shape) when its non-coding sequence binds to an appropriate Protein or chemical target
Pseudogene	class	incomplete copy of a Protein-coding Gene; can yield RNA which controls the expression of the Gene

The genomic machine consists of Recombinant DNA, Active RNA, and Epigenetics:

Name	Kind	Description
Methyl Tag	class	methyl group attached to DNA, usually suppressing a Gene (e.g, to defend against a Transposon)
Transposon	class	Gene which clones itself into other Chromosomes, thereby suppressing or amplifying other Genes
Acetyl Tag	class	acetyl group attached to Chromatin, usually amplifying nearby Genes
Chromatin	class	DNA-binding Protein in a Chromosome; its shape can suppress a Gene by making the DNA inaccessible or attracting repressor Proteins

Source: Molecular Cell Biology, H. Lodish et al., 1995 (Scientific American Books).

Last modified: 12/18/2003