Specificity of the Adaptive Immune System
Each lymphocyte has only one type of epitope receptor, but pathogens have many potential antigenic molecules, each of which may have several epitopes. In addition, the epitopes for some pathogens, such as those on influenza's hemagglutinen protein, change from year to year as a result of mutations. Consequently, the number of possible foreign epitopes is enormous, but the human genome only has about 30,000 genes. In view of this, how does the immune system manufacture all of the lymphocyte receptors needed to recognize so many different epitopes?
Answer: This is accomplished through gene spicing.
In most cases, a single gene encodes for a single protein.
However, lymphocyte receptor proteins are produced by a different process. The stem cells that produce lymphocytes have a pool of 300-400 genes which encode for peptides in lymphocyte receptors. During development and maturation of lymphocytes, most of these genes are eliminated, and only 5-6 randomly selected genes are retained and spliced together. This spliced sequence encodes for receptors in the mature lymphocytes.
The pool of receptor genes in stem cells is like a deck of 300-400 cards. Each lymphocyte that is produced is dealt 5-6 of these at random, and the 5-6 genes can be shuffled into any order before they are spliced together. As a result, it is possible to synthesize a hundred million different receptors from the original pool of 300-400 genes. When it matures, each lymphocyte can manufacture just one type of epitope receptor.
This short video summarizes the process by which specific antibodies are made.
Self-Tolerance Through Lymphocyte Selection
How does the immune system avoid attacking our own cells which also have potentially antigenic shapes?
As a result of the random selection and splicing of 5-6 genes to create unique receptors, some of the lymphocytes created will have receptors that would bind our own proteins. However, during the maturation process in the thymus gland, those lymphocytes are induced to undergo apoptosis (programmed cell death), and they are permanently eliminated.
Autoimmune diseases, such as rheumatoid arthritis, lupus, & juvenile (type I) diabetes result when self-tolerance fails and lymphocytes attack our own cells.