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Another Layer of Defense: The Adaptive Immune System

Medical concept of cancer. 3d illustration of T cells or cancer cells.

Editor’s note: Physicians have a special place among the thinkers who have elaborated the argument for intelligent design. Perhaps that’s because, more than evolutionary biologists, they are familiar with the challenges of maintaining a functioning complex system, the human body. With that in mind, Evolution News is delighted to offer this series, “The Designed Body.” For the complete series, see here. Dr. Glicksman practices palliative medicine for a hospice organization.

the-designed-body4.jpgThe body is constantly under attack from powerful microorganisms that, if given the chance, will invade and take over. The body’s first layer of defense is the skin and epithelium that lines the respiratory, gastrointestinal, and genitourinary tracts. If the microbes get past this barrier, they come up against the body’s immune system. The immune system can be divided into the innate immune system,which each of us is born with and acts in the same way every time it encounters foreign matter, and the adaptive immune system which develops over time and reacts in a specific way to the foreign matter it is encountering.

Without the first layer of defense or both components of the immune system, our earliest ancestors could not have lived long enough to reproduce because they would have died from overwhelming infection. In the last several articles in this series, I have detailed how the cells and proteins of the innate immune system work. But on their own, they are incapable of defending the body from pathogenic microorganisms. Now we will start to look at the adaptive immune system, which brings extra intelligence, firepower, and precision accuracy to the field of battle to help the rest of the immune system get the job done.

The cells of the adaptive immune system are called lymphocytes and are produced in the bone marrow. The B-lymphocytes (B-cells) stay in the bone marrow to mature and the T-lymphocytes (T-cells) enter the blood and migrate to the thymus. The thymus is located inside the chest between the breastbone and the heart and is not to be confused with the thyroid gland, which is in the neck and secretes thyroid hormone. Once inside the thymus, the T-cells develop further and become subdivided into helper T-cells and cytotoxic T-cells. Since the lymphocytes come from the bone marrow and the thymus, these regions are known as primary lymphoid tissue.

Using about a thousand different receptors, each of the immune cells of the innate system can detect about a thousand different chemical patterns present on the surface of invading microbes. These cells activate when their receptors lock on to these foreign chemical patterns. Therefore, although the cells of the innate immune system can only detect a limited number of different chemical patterns, they all have the same ability to do so. This means that when they sense the presence of an intruder, all of the cells of the innate immune system can start to work together as a large fighting force.

In contrast, each lymphocyte has about a hundred thousand identical receptors on its surface, which can only detect a very small chemical pattern. This is usually just a few amino acids from within a very large protein molecule on the surface of a microbe. The first cells of the adaptive immune system to be understood were the B-cells. When B-cells activate by having their receptors lock on to these small chemical patterns on a microbe, they produce millions of specific proteins called antibodies.

Each of these antibodies has the same small chemical pattern as the specific receptors on the surface of the B-cell that produced it. Contact with one of these specific small chemical patterns on a microbe was responsible for generating specific antibodies from a B-cell, so scientists call them antigens. The word antigen is a shorthand term for an anti(body) gen(erating) small chemical pattern on a microbe which can cause an immune response from B-cells or T-cells. As opposed to the immune cells of the innate system, which can only detect about a thousand different chemical patterns, it is estimated that altogether, the cells of the adaptive immune system can detect about ten billion different antigens.

A lymphocyte activates when its specific receptors lock on to the specific antigens on the surface of a microbe. But, since each of the ten billion different lymphocytes can only detect one specific, small chemical pattern on a microbe, when they activate, there are too few of them around to provide an effective defense for the body. In other words, altogether, the cells of the adaptive immune system, with their ten billion different receptors, are much better at detecting foreign invasion than the innate immune system, with its one thousand receptors, but not as good at mounting an immediate response. The job of the adaptive immunity requires much more time than the one of innate immunity, because it must take the specific information it has detected about the pathogen, integrate it, and then use specific effector cells to bring about a more effective defense.

On its way back to the bloodstream, the fluid in the lymphatics travels through tissue that contains collections of lymphocytes. In this way, the lymphocytes are exposed to antigens from microbes that are present within the lymph that is draining all the organs and tissues of the body. These regions are called the secondary lymphoid tissue and consist of the lymph nodes, the spleen, the tonsils, and adenoids and the appendix. After they mature, lymphocytes migrate back and forth between the blood and the secondary lymphoid tissue, patrolling for foreign antigens.

Each helper T-cell has about a hundred thousand specific T-cell receptors on its surface that can detect only one specific antigen. Upon digestion of microbes in the tissues, dendritic cells and macrophages from the innate immune system migrate to the secondary lymphoid tissue. By placing some of the foreign protein they just digested on their surface, they present it to passing helper T-cells to activate them. Then the dendritic cells and macrophages release cytokines that enable the helper T-cells to grow and multiply into thousands of identical clones. This process converts the naïve helper T-cells into effector helper T-cells. These have no direct killing power, but regulate the immune response by releasing cytokines that attach to specific receptors on other immune cells to improve their killing ability and help them multiply.

Since there are only a limited number of cells in the adaptive immune system that can identify a specific microbe, it is important for them to be able to increase their population quickly in response to attack. In addition, some of the activated helper T-cells remain within the lymph nodes to act as memory cells so the immune system can respond faster the next time. The immune system demonstrates a measure of intelligence through helper T-cells. By knowing which specific reserves to multiply and mobilize in defending the body both during the present and future infection, it is able to adapt over time.

Just like the helper T-cell, the cytotoxic T-cell also has about a hundred thousand specific T-cell receptors on its surface that can detect only one specific antigen. After migrating to the secondary lymphoid tissue, dendritic cells that are infected with a virus or bacteria place foreign antigens on their surface so that a passing naive cytotoxic T-cell can attach to it and become activated. With the release of cytokines from either the dendritic cells or nearby helper T-cells that have responded to the same antigen, the cytotoxic T-cells grow and multiply into thousands of identical clones. The effector cytotoxic T-cells are now able to destroy any other host cell that has been infected by the same virus or bacteria. They use their specific receptors to identify and attach to the foreign antigens on their surface and then release deadly chemicals and enzymes to kill them and prevent the spreading of infection.

Like all lymphocytes, B-cells are made in the bone marrow, but unlike T-cells, they remain there to mature. Once released, they migrate back and forth between the secondary lymphoid tissue and the blood patrolling for antigens. Each B-cell has about a hundred thousand specific B -cell receptors on its plasma membrane that allow it to identify and attach to just one specific antigen. The molecular structure and shape of the part of the receptor that attaches to the antigen is identical to the antibodies the B-cell will produce when it activates. Unlike T-cells, B-cells do not need other cells to present them with antigens and when an antigen attaches to its specific receptors, it is brought into the B-cell.

The captured antigen is then processed and placed back onto the cells surface. When the now activated B-cell connects with an effector helper T-cell that has been activated by the same antigen, the latter releases cytokines that attach to receptors on the B-cell and stimulates it to multiply and become numerous identical plasma cells. Each of these plasma cells can produce millions of identical antibodies, shaped to react to the specific antigen that started the immune process in the first place. In addition, just like for the effector helper T-cells, some of the effector B-cells become memory cells that are stored in the secondary lymphoid tissue so the body can react faster the next time it becomes infected by the same microbe.

Just as a walled medieval town had to have enough defenders to prevent itself from invaders, so too, the body’s immune system must have enough specific cells and proteins to protect itself from serious infection. We have seen that without the right amounts of each of the cells and proteins of the innate immune system, our earliest ancestors could not have survived long enough to reproduce. The blood must have at least 500 million helper T-cells per liter to be sure that there’s enough help for cytotoxic T-cells to kill enough infected cells and for B-cells to produce millions of different antibodies which altogether can detect about ten billion different antigens. How do we know this? HIV.

HIV, or human immunodeficiency virus, targets helper T-cells and when chronic HIV infection causes their level in the blood to drop below 200 million per liter, the person is said to have AIDS (acquired immunodeficiency syndrome). A person with HIV-AIDS usually has not only severe infections caused by the usual pathogenic microbes, but also opportunistic infections. These infections usually do not cause infection in a person with normal immunity. HIV-AIDS can affect almost every organ system in the body and often results in the formation of different types of cancer as well. Having a helper T-cell blood count below 200 million per liter is not sufficient for allowing the adaptive immune system to do its job and is equivalent to not having enough defenders to help protect a walled medieval town from invasion and destruction. The result: usually death from overwhelming infection and sepsis.

Evolutionary biologists have imaginative theories about how the adaptive immune system came into being, but none of those really accounts for all of the irreducibly complex parts needed for it to work properly, nor the natural survival capacity needed to assure that there are enough of each of them to survive. Next time we will look at how the proteins of the adaptive immune system, the antibodies, work to provide the body’s defense with additional intelligence, firepower, and precision accuracy.