Immunogenetics

I.
The Immune System has two major branches. Although there are significant differences between the operations of the two branches of the immune system, they are similar in many key ways, including the problem of manufacturing antigen-specific recognition proteins. Understanding how the humoral system works tells us a great deal about the cell mediated system
A.
The Cell Mediated Immune Response utilizes T lymphocytes. In general these cells direcly engage invading foreign objects and substances.
B.
The Humoral Immune Response utilizes B lymphocytes which manufacture proteins called antibodies. Antibodies are designed to specifically identify and tag foreign antigens. These antigenic objects are then destroyed by phagocytes (another kind of lymphocyte).

II.
The Immune Response occurs in two stages.
A.
The Primary Immune Response occurs the first time your body is exposed to a new antigen (such as a newly encountered virus or bacterium).
1.
Since your immune system has never encountered this particular enemy, it must first learn how to tailor a specific antobody to attack this antigen.
2.
This process occurs in a special group of lymphocytes (one type of white blood cell) in the bone marrow. These special cells are stem cells.
3.
Once a group of stem cells has created the corect antibody for this antigen, it will begin to give rise to new lymphocytes which are all specialized in the production of this single antibody.
4.
In the early part of the primary immune response, the invading organism is largely unchallenged. This is the period of time during which you actually may get sick.
5.
As the programmed stem cells produce more and more specialized B lymphocytes, the production of the correct antibody also increases. This is the period of time during which you begin to recover from the illness.
6.
Along with the active B lymphocytes, the programmed stem cell will also produce a group of long lived B lymphocytes called memory cells. These remain in the bone marrow for many years.
7.
Once a B lymphocyte is programmed to produce a particular antibody, it is specialized for the rest of its life. It cannot be reprogrammed to produce a different antibody.
B.
The Secondary Immune Response occurs any time you encounter an antigen after the first time.
1.
If an antigen invades your body for a second time, you will already have in your bone marrow memory cells which are programmed to combat that antigen.
2.
These memory cells will immediately begin to manufacture new B lymphocytes, which immediately begin to churn out specialized antibodies.
3.
These antibodies will immediately begin to combat the antigen.
4.
This happens much more rapidly than the primary response. This is the basis of immunity. The second time you encounter the same antigen, you probably don't even know it; your immune system defeats it before it has a chance to make you feel sick.
5.
Each time you encounter the same antigen, it renews your supply of memory cells.
C.
Vaccination is meant to elicit a primary immune response without making you sick. There are several ways this is done.
1.
You could be injected with a damaged or weakened (attenuated) virus. this is relatively dangerous, because there is a reasonable possibility tha the vaccination could actually give you the disease you are trying to prevent.
2.
More commonly today, vaccines contain heat-killed viruses. The immune response is excited by the protein coat of a virus, not its nucleic acid, so the viruse doesn't have to be alive.
3.
A newer technique is to manufacture the viral coat protein in vitro, and inject just the protein. This is the safest technique, since it doesn't involve whole viruses (even dead ones).

III.
One of the puzzles of human genetics has been that the body is capable of manufacturing more kinds of antibodies than humans have genes. In recent years, the mystery of how this is done has been solved.
A.
Each antibody is composed of two light chains and two heavy chains, associated in a kind of Y-shaped fork configuration.
B.
Each of the chains is composed of two parts, called the constant region and the variable region. The variable region has one (light chain) or three (heavy chain) portions.
C.
In the human genome, there is a fairly large section of DNA which is devoted to the sequences of DNA necessary to code for these various regions. There are only a few kinds of constant regions, but the variable regions come in an apparently limitless variety of combinations.
D.
When the lymphocyte is stimulated to design a specific antibody to match a specific antigen, these genetic sequences are literally cut and pasted into a unique, contiguous gene for the production of either a light or a heavy chain. The portions of the DNA from this region which are not necessary for the production of this custom-designed antibody gene are cut away and discarded.
E.
Thus, once a B lymphocyte is programmed to produce a specific kind of antibody, it cannot be reprogrammed; it has thrown away the choices for variable region genetic elements which it did not use, and they cannot be regained.
F.
Exactly how the stem cell determines just which of hte variable sequences to keep and which to discard is not yet completely understood.