The “Evolving” Immune System

Sean D. Pitman M.D.

© Aug. 2001

Everyone has experienced sickness at one time or another in his or her life. However, most people get better and often do not get that same “bug” again. Why is this? There are literally millions and millions of “bugs” and other things in our everyday environment that can make us sick. Why then do we generally remain so healthy? The reason is because most of us have a highly effective “immune system”. Those, whose immune system is not functioning well, will certainly have a lot of problems. The famous HIV-virus stands for “Human Immunodeficiency Virus.” This virus causes the disease AIDS… or “Acquired Immune Deficiency Syndrome.” A person with AIDS has a very weakened immune system. Because of a lack of immunity, “bugs” that other people never get infected with, infect an AIDS victim. Eventually, these infections kill their host. Now that we understand just how important it is to recognize bad “bugs”… just how does the body become capable of recognizing the millions and billions of things that can make us sick?

Surprisingly enough, it is through a process of natural selection. In our bodies we have cells that are specialized immune cells. They go to “school” to learn what not to kill… self … or their own host body. But how do they recognize what is self and what is not self? These cells recognize certain molecules (antigens) that are on the surfaces of all “self” cells in their own body that they are to protect. They sense or “feel” these molecules with their own molecules called antibodies. Those immune cells that do not recognize self-antigens, are killed off before they get out of school. It is a tough school indeed if the students do not learn their lessons! Those cells that do recognize self-antigens graduate to go and search the body for non-self antigens. However, each immune cell only has one type of antibody, so it can recognize only a specific antigen. Since there are millions and billions of different possible antigens, how do the immune cells cope with such a variety of enemies? Well, there are millions and even billions of immune cells produced by the body. Each of them will recognize a different non-self antigen. Chances are, that if a non-self antigen gets into the body in a significant amount to cause sickness, at least one of the immune cells will recognize this non-self antigen as foreign. When this happens, the immune cell sounds the alarm that the body has been invaded. The foreign body with the non-self antigens on it is attacked. However, if not too many immune cells recognize the foreign body, the initial attack might be rather weak. The sickness may linger on for some time before the body can kill off the offending “bug”. However, the immune system remembers this particular bug for the future so that the body can kill it much quicker if it ever sees this antigen again. The immune cell that recognized the antigen clones itself to make many identical copies of itself. Now, there are many immune cells that will recognize this particular foreign antigen. If infected again by a bug with this particular antigen, the body is ready and kills it much more quickly… making it immune to this particular bug. This is how vaccines work. A vaccine presents the body with the antigens of either a dead or a weakened bug. In this way the body can prepare to kill that particular bug without first having to go through the sickness that the bug may causes.

Many people, including scientists, say that this process is evolution in action. Is this actually true? After all, this system does use survival of the fittest (immune cell) and natural selection… and creates incredible diversity of antibody types. Is this not evolution on a small scale? Is this not representative of what we see in the rest of nature… the incredible diversity through competition between “kinds” in the animal and plant kingdoms? Lets take a look and see.

The first question that needs to be asked is just why there are so many different immune cells with different antibodies. How did the immune system in a single individual come up with so many different antibodies to begin with? I mean, it had no previous knowledge about all the evil antigens in the world or just which ones it might have to combat with. So, how did it get its gigantic arsenal of options? The answer lies in the DNA.

Antibodies are proteins and so they are coded for by DNA. Antibodies are Y-shaped molecules with two different protein strands called heavy and light chains. At the tips of the V-end of the Y there are “variable regions” on both the light and heavy chains that can be different from cell to cell. The rest of the antibody does not vary in its protein sequencing. Each of the two chains (heavy and light) is coded for by DNA in sections. Before a cell is chosen to become an immune cell, each section of DNA has many genes that can code for part of the final antibody for that cell if it becomes an immune cell. Even though there are many options or genes for each section, only one gene will be chosen. This choice is by random recombination of one gene from each section. For light chains there are about 250 V-segments (or separate genes in the original DNA), four J-segments, and three different ways that a V-segment can join to a J-segment when the DNA is spliced. The final product for a light chain in DNA is one V-segment (gene) followed by a single J-segment (gene). This makes up the “variable region” of the light chain. The constant region of DNA for the light chain follows this region. The rest of the genes are not read for that cell. For the heavy chains, there are about 250 V-segment genes, 15 D-segment genes, and 5 J-segment genes… followed by the constant region genes. Just like in the light chain DNA, only one gene from each segment is chosen for the final splicing of DNA so that just one V-gene is followed by one D-gene, which is followed by one J-gene. This makes up the “variable region” of the heavy chain. The constant region follows just like in the light chain.

The large number of different genes and their different possible combinations make the huge variety of antibodies possible. This number can be calculated as follows: For light chains there are 250 V-segments, 4 J-segments, and 3 possible joining frames. This gives a total of 250 x 4 x 3 or 3000 different kinds of complete light chain possibilities. For heavy chains there are 250 V-segments, 15 D-segments, 5 J-segments, and 3 different joining frames. This gives a total of 250 x 15 x 5 x 3 or 56,250 different kinds of complete heavy chain possibilities. Combining the chains gives 1.7 x 10⁸ (170 million) different possible antibody specificities.

Certainly this is a huge variety, but is it an example of the modern theory of evolution at work? Lets draw some parallels and see. In the current theory of evolution, one type of animal evolves into another type of animal over time. This happens when that animal has a mutation in its DNA that creates a different protein, which works better for a particular environment. This mutation is passed on to its offspring who in turn have other mutations, one of which may give an advantage and is therefore preferentially passed on… and so forth. In the immune system scenario, our specific “animal” is the antibody. Nature uses the foreign or non-self antigens, which match a particular antibody, as a selection tool. This antibody has now been selected by nature to make more of its exact self… NOT mutated or changed in any way. In fact, if the antibody were changed after cloning, it would not be helpful to the body. Therefore, the antibody (animal) does not change in its succeeding generations or “evolve.” In the immune system there is no evolution at all. All the different “kinds” of animals (antibodies) were made “in the beginning” by the body… BEFORE natural selection by nature. In other words, the body made all the millions of kinds of antibodies (animals) suddenly… without the influence of natural selection or exposure to any external factors. After the creation and education of the immune cells, each with a different type of antibody, there is no evolution of antibodies in the body. An immune cell does not gradually change the antibody that it produces over generations. If it did, then it could not perform its intended function or remember what it is looking out for. This is actually less varied than in the animal world. In the animal world, an animal’s offspring can change through Mendelian variation, but not in the immune cell world. Once an immune cell is born, educated, and is making a particular type of antibody, neither it nor its “offspring” or clones change the type of antibody that is made… unless the clones of itself that are made are somehow mutated… in which case they would not be helpful in defending against a previously recognized threat.

So, we see that even though the immune system does undergo natural selection and survival of the fittest, just like in the animal and plant kingdoms, this is not an example of evolutionary theory in action. Natural selection and survival of the fittest actually work against differentiation through mutation… as a rule. The great varieties within “kinds” in the animal and plant kingdoms can easily be explained by “preprogrammed” or inherent genetic abilities for variety… as studied by Gregor Mendel. Similarly, the immune system has inherent abilities for genetic or preprogrammed variety… not related to the modern theory of evolution or dependent on mutation. The varieties in both worlds are dependent upon preprogrammed genetic codes, which are incredibly complicated and specific. The genetic shuffling of codes themselves follows very strict rules that are extremely complicated, but are in no way evolving beyond what are already preprogrammed and predictable changes.

1. Stryer, Lubert. Biochemistry, 3^rd ed., 1988, pp. 904-909.