If you heard that a very destructive creature was in your village, what would you expect this creature to look like? Perhaps a ferocious cat, or a colossal beast that was capable of leveling whole buildings? Such a creature does exist in Africa, except it is a single celled bacterium by the genus Trypanosome, a microscopic creature with the capacity to strike fear into the heart of virtually an entire continent. Living a segment of its life as a parasite in the bloodstream of humans and other mammals, Trypanosome can trigger a lethal neurological disorder in the circulatory system. It has also been found that it is the cause of a serious sleep disorder in humans. The disease can ruin a person’s circadian cycle, cause fevers, and changes in personality. Unfortunately, about 60 million people in 36 of the 52 countries in Africa are at constant risk.

Another significant role in the lifecycle of trypanosomiasis is the tsetse fly, the bacteria’s most common intermediate host, which transports the Trypanosome from one mammalian host to another. Trypanosomiasis is endemic in a large area of approximately 3.8 million sq. mi. in Africa, where both the parasitic disease and the tsetse fly coexist. Moreover, the danger is not limited to humans because it also affects many other mammal species, most notably livestock and horses. Malnutrition often follows as a direct consequence when large swaths of animals are killed by trypanosomiasis, as there will be less meat and dairy to consume.

The trypanosome parasite invites disease for the host mammal by collapsing or neutralizing its immune system. Let us first remember how the immune system works:

The immune system

Every living thing is provided with two things: food and protective systems. Immune system is one of these vital systems. Most immune systems across mammals function in similar ways; Antibodies are produced to destroy toxic substances and antigens on foreign bacteria, fungal cells, or the virus sheath invading the body. These antigens can be found on the infected foreign cells and have a unique shape and structure according to the organism that causes each disease. The immune system binds to the antigens of the foreign organism in the same manner as a key-lock system with its antibodies produced while fighting against the disease, thus neutralizes the invading organism.

Most of the antigens, which reveal the identity of a foreign being, are structures created of proteins, polysaccharides, or protein-based fats. Our immune system has the sensitivity and the capacity to produce an infinitely diverse variety that can discern even quite identical but foreign substances bearing antigenic properties for our body. To draw an analogy, a specific antibody can be produced for each speck of dust on Jupiter. Our immune system is blessed with the ability to synthesize appropriate antibodies by selecting proteins that differ in type or location of one amino acid.

The mechanism of binding of the antibody to the antigen is carried out with effective economy, because each type of antibody is produced specifically against a particular antigen. This mechanism works like a key-lock system, so the body recognizes its own cells and does not attack them. Each antibody produced in the immune system is created in a three-dimensional, one-to-one compatible structure with the antigen that causes it to be produced, and easily recognizes and locates it, binds as the key fits into the lock, and thus renders it harmless by disrupting the chemical structure of the antigen.

Trypanosome and the immune system

The case of trypanosome vs. the immune system is somewhat exceptional. The abovementioned almost universal immunity principle does not work against trypanosome. Even though parasites are constantly exposed to the mammalian immune system in the blood, they constantly change the antigen that forms the surface sheath. They thwart the host’s defense, as if rapidly changing their password so that it can never be guessed. Until the immune system produces new antibodies to bind to new antigens, some of the trypanosomes discard their sheaths and drape themselves in another one. If this condition persists, the immune system of the host cannot cope with the infection and may succumb to it.

This extraordinary phenomenon astonishes the scientific community and many scientists are investigating the molecular structure of antigen diversity extensively in African, European, and US laboratories. These parasites are only 0.015–0.030 mm in size, and its two most notorious species are Trypanosoma rhodesiense and Trypanosoma gambiense, which inflict serious damage on the human body.

Like many other parasitic species, the life cycle of trypanosomes is very complex. In each phase of this life journey, the parasite takes different forms and exhibits different characteristics in such an unusual way that generates curiosity. The life cycle can be summarized as follows: when the tsetse fly bites a disease-bearing mammal, the trypanosomes in the mammal’s blood are sucked up and settle in the middle intestine of the fly. They undergo a series of complex processes including several structural and biochemical changes. After about three weeks, the trypanosomes appear in the fly’s salivary glands in a disease-bearing form. Meanwhile, they are also draped in new surface sheaths.

When the secondary host fly bites a healthy person, the disease-causing trypanosomes enter the blood of the new host. In this new stopover, parasites are transformed into a form in which they can rapidly multiply. First, they wreak havoc in blood vessels and on lymph nodes, causing fever, marks and swelling in the body. At this stage, a constant struggle with the host’s immune system ensues. A likely invasion the patient’s central nervous system by the trypanosomes can cause intense drowsiness, coma, and eventually death.

In years of research on the trypanosomes, the thick surface sheath covering the cell membrane of the parasite was first described in 1965 by Keith Vickerman of the University of Glasgow. Shortly thereafter, different surface sheaths were discovered in different trypanosome clones. In 1968, Richard W. F. Page from the Molteno Parasitic Research Institute in Cambridge analyzed and decoded the isolated antigenic surface proteins from several clones, revealing that each clone had a biochemically different protein. The clarity of these differences suggests that each antigen is expressed by a different gene. In the 1970s, George Cross and his colleagues found evidence supporting Le Page’s proposal. These antigens are now called Variable Surface Glycoproteins (VSG). As a result of subsequent research, the picture became even more clear.

Once the infection has begun, antibodies are formed in the host’s immune system that bind to the variable surface glycoproteins that appear on the surface sheath of the invading parasites. These antibodies kill most of the initial trypanosomes. Yet interestingly, on a few remaining trypanosomes a new sheath to which antibodies cannot bind is built, and the trypanosomes evade the immune system’s grasp. The survivors induce a new population producing new variable surface glycoproteins. This time, the immune system produces new antibodies against these freshly constructed antigens. Meanwhile, the parasitic population grows. Newly produced antibodies are able to kill 99% of new parasites again. However, until that time, the parasitic group constituted by about 1% of the survivors has already changed its sheath. Hence, another population begins to multiply. This process of life being a struggle unfortunately continues until the host mammal dies.

The mechanisms of antigen diversity in trypanosomes are very complex and variable, and the total capacity to produce varieties is not clearly known. Recombinant DNA technology is used to investigate the structure of the genes for producing variable surface glycoproteins, the mechanism of cell membrane binding, and the selection and expression of one of the codes. In addition to the four licensed medicines produced for the treatment of parasitic diseases, new drugs are being developed.

It is astonishing that this tiny window of invisible dimensions has such a huge potential opening to different branches of science. Many such exceptional and precise situations exist in the universe that may showcase contradicting mechanisms with general principles and procedures. Sometimes we may wonder why God creates such harmful parasites. Since we do not know the performance at every point of an entire ecosystem with our insufficient scientific knowledge, limited sensory organs and temporary observation, we tend to see any seemingly harmful being as futile and devoid of wisdom and immediately raise our voices in protest. However, with new discoveries in science, thousands of wise meanings may be extracted from a creature we generally take for granted.

References

Lori Peacock, Simon Cook, Vanessa Ferris, Mick Bailey, Wendy Gibson (2012): The life cycle of Trypanosoma (Nannomonas) congolense in the tsetse fly, Parasites & Vectors, 5:109 www.parasitesandvectors.com/content/5/1/109.

Michael P Barrett, Richard J S Burchmore, August Stich, Julio O Lazzari, Alberto Carlos Frasch, Juan José Cazzulo, Sanjeev Krishna, (2003): The Trypanosomiases, The Lancet, Vol 362, November 1, Pages 1469-1475, www.thelancet.com.

www.cdc.gov/dpdx/trypanosomiasisafrican/index.html

I, the protective system that you call the “immune system,” am divided into different groups and sections, each of which has its own area of expertise. Just like a military unit, each of my groups has to be partially or fully trained before it begins life in my system so that it can properly fulfill its defensive function. “Soldiers” in this protective troop work according to what expertise they have and the type of “enemy” (alien microorganisms) they encounter. Some are equipped with heavy weapons against tough enemies; some produce a special poison with which they kill their enemies by injecting it into their bodies, some work like a waste disposal, smashing up the dead bodies of the enemies, and some of them eat the alien intruders alive when they attack your body. Others produce raw material to arm your body, some turn that material into weapons, some work as defenders, some are signalers, some are rangers and some are equipped with a special intelligence which allows them to recognize the previous invaders and destroy them more easily at their future encounter. In this intelligence system, which works like an information center, the soldiers check the dangerous invaders and remember their previous experience with them. Then, they develop a strategy to fight against those invaders. If the enemy is known well, the defense against it will be easier.

Now, using this analogy, I will talk about your enemies and the features of my soldiers that are placed in your body to fight against them. However, I have to remind you of something first: as you know, every army has to have a top commander. Similarly, there is someone who has placed such a perfect system like me in your body, someone who has boundless knowledge and power, and has no one else superior to Him or has no one to receive orders and instructions. That is our Lord God Almighty. Since He knows very well what kinds of enemies you will face, He has created me with all my troops so that you can be defended against those enemies.

The enemies of your body are germs, which enter your body through different passage ways, including digestion, respiration, excretion and the skin. “Germ” is a general term referring to many kinds of micro-organisms. Some of them are bacteria, some are fungi and some are viruses. Your body needs different special tactics to defend against each group of germs and my soldiers are quite talented in those tactics. I have to be always watchful against germs coming from outside. Not only that, but I also have to be careful about inner enemies, that is, the cells in your body which suddenly turn into “terrorists” becoming harmful and spoiling the system. You call those cells “cancerous.” It is a great challenge for me to cope with those cells because they originate from among your very own cells and they know our tactics very well. Nevertheless, with God’s help, we can defeat them. However, when too much stress and anxiety weaken me I might miss some of those cancerous cells, which will grow and become tumors. In fact, cancerous cells develop much more in number than is commonly known. But my soldiers constantly check every single cell that is formed in your body and try to see whether it is normal or not. As soon as they discover a cancerous “terrorist” cell, they try to quickly destroy it. However, some cancerous cells are disguised like a wolf wearing a sheepskin so that they can avoid detection. My soldiers make rounds and check the cells from outside by only looking at their skin. Thus, they can be manipulated. All of your cells, including those with germs or cancer, contain protein with a special code which identifies the cells as being yours. When my soldiers encounter our fellow cells carrying those coded proteins, they release them. But the enemies who do not carry this code (or password) are immediately caught and destroyed. When we have diseases like cancer, however, the cancerous cells may evade our “rounds man” because they know this password. Sometimes the opposite may happen: my soldiers get confused and cannot identify their fellow cells despite carrying the right password, assume that they are enemies and start to attack them. These types of diseases, called Autoimmune diseases, emerge with a quite complicated mechanism which is a puzzle even for me! For example, during rheumatoid arthritis, which is among the many long-lasting and unrecoverable diseases, my soldiers attack and gradually destroy the tissues like cartilage, cardiac muscle, eye lenses, and the tubes of the kidneys with which they share a body. In fact, when we are created as a whole system (when you are only an embryo in your mother’s womb), some of my soldiers make an agreement with the other cells of your body, announcing that they will forever stay friends with them, will show tolerance to them and will only attack the enemies. But, somehow this agreement is broken later; my soldiers do not obey me anymore.

Now it is time for my group of soldiers to introduce themselves:

The most general term by which we are identified with is white blood cells or leukocyte. We appear approximately 6,000 to 7,000 times in each cubic millimeter of human blood. The other blood cells, which are called red blood cells (erythrocyte) are red in color; it is for this reason that we are called white. Since blood vessels can reach to the remotest edges of the body, we roam around the body through those vessels and look for work to do. Of course, not everyone can do everything. So, we are first divided into two sections. The cells in the first section contain microscopic granules, so they are called granular leukocyte. The cells in the second section do not contain such granules, so they are called agranular leukocyte. Those sections are divided into groups among themselves. The first section has three groups: neutrophils, eosinophils and basophils. The second section has two groups named monocyte and lymphocyte.

Eosinophills: You may not know much about these soldiers that make up 12% of the whole protective body. However, during allergic reactions and diseases caused by parasites, the number of these soldiers increases. They complete the effect of the antibodies produced against the antigens. Some chemical substances like histamine appear as a reaction to antigens, such as itchiness, rash, and swelling. Eosinophils reduce the effects of those substances and the symptoms.

Basophils, which are the least in number, make up the 0.5% of the body. Those soldiers are present mostly in the scars that are healing or in highly infected areas. The granules inside basophils contain two very important substances called heparin and histamine. Histamine helps expand the blood vessels and accelerates the release of active substances within me from the blood vessel walls, enabling them to reach to the affected area. Heparin also prevents the blockage of blood vessels because of blood clot.

Lymphocytes of the second section are the group of soldiers which goes through special training and has expertise in many subjects. They make up 20-25% of the soldiers in my system. Those soldiers detect antigens and germs and remove them from the body. Every soldier has a detector which identifies a certain antigen. Therefore, in your blood, there are millions of lymphocyte soldiers, which are different from each other and do not have a pair. For any antigen of a germ, you will definitely find a lymphocyte that finds and kills it. Those soldiers can be grouped according to their appearances, as small, medium, and large lymphocytes. Each group has different special features. We can also divide them according to their maturation and training process as B-lymphocytes and T-lymphocytes. Although both of them originate from stem cells in the bone marrow, T-lymphocytes mature in the thymus before they move to the other lymph tissues such as the spleen, liver, and tonsils (Thymus is a gland in the chest that talked about itself in the previous issue). B-lymphocytes, however, mature in the bone marrow, and go directly to the tonsils, appendicitis, spleen and other lymph tissues. When the T lymphocytes mature in the bone marrow, they acquire different new features. Some of them work as T helper cell, some work as natural killer T-cells and some work as suppressor T-cell. A helper T-cell, which is triggered by an antigen that is specific to it, secretes lymphokines, which makes B-cells produce antibodies. Among those lymphokines, interleukin-2 activates the natural killer T-cells, which kill the infected cells. The killer T-cells do not bind directly to an antigen. Rather, they secrete a substance that kills the infected cell after joining with the antibodies that were previously bound to the infected cells. On average, T-cells live 2-4 years; some, however, live more than 10 years. Today, the defense mechanism of the T-lymphocytes creates an issue in terms of organ transplantation. If, for some reason, a foreign organ (a kidney or heart, for example) is transplanted into the body, the T-lymphocytes attack that organ immediately. Those “headless” soldiers do not know that the body really needs that organ and try to eliminate it, therefore, leading to transplant rejection or tissue incompatibility. The T-lymphocytes treat the foreign organ the same way as they do to the cancerous cells: they attack and try to destroy it. For this reason, the immunologists are trying to discover medicines that will help them control the soldier T-lymphocytes whenever they need to be stopped.

Dear Peter, have you ever thought about how all this happens? While you have no idea about a germ that might enter your body, those memory cells, which are placed in your blood with a boundless compassion by our Creator, remember an enemy that they saw years ago, and begin to make weapons right away. Since those cells are devoid of reason and consciousness, to operate them there has to be Someone with a great knowledge and will.

The lymph nodes are production centers for the lymphocytes found at some particular places in the body. They resemble variously sized military headquarters. The lymphocytes are produced mostly at infection sites, which are the little lymph tissue groups located under the epithelium that lines along the walls of the digestive tube, respiratory track, and the bladder. When fighting with bacterial infections the lymph nodes swell and enlarge as much as 1–2 cm. In addition to the lymph nodes that extend through the lymph vessels, the areas such as nape, groin and the axilla (underarm) also contain lymph nodes. If you get an upper respiratory tract infection, the lymph nodes at your tonsils and neck areas become swollen. If you get a urinary track infection the nodes in your groin area become swollen. As for digestive track infections, it is the responsibility of the lymphocytes in your appendix to fight against germs. Some scientists view this organ, which is an extension of the cecum (the blind gut), as a “dead” piece of intestine. Both the appendix and tonsils are quite useful organs that produce lymphocytes in normal circumstances; they are not some useless remnants. For that reason, it is not right to remove them when it is not really necessary. However, we have to remember the proverb that says, “We salt the food so that it does not smell bad; but, what do we do if the salt itself smells bad? Then, we have to get rid of the salt.” Similarly, in some bodies where my system is weak and so is lymphocyte production, those areas become home to germs and you have to remove them.

Other than the soldiers of the immune system, several organs in your body have their own ways of protecting your body. Those organs do not have soldiers like in my system; theirs are like a “civil defense.” Chief among those are your skin which works as a natural barricade against the entrance of the germs, the mucous membrane that lines along the walls of your mouth and inner nose, interferon which is a substance produced by your cells against viruses, and an antibacterial substance called lysozyme which exists in your tears and sweat. Therefore, sweating, crying, and runny nose are not things to be ashamed of; they are only the protective systems that have been naturally placed in your body by our Lord God.

Dear Peter, I think I should stop here although there are still so many features of me that you have to discover. After all, beneath all diseases and deaths you will find disorders related to me. The biochemical processes in which many of my soldiers operate are not exactly known yet. If those are revealed, doctors will likely succeed in healing many other diseases. However, sooner or later you will reach the destined end: death. No creation can be immortal; there will definitely be a problem and you will have to leave this world, wherein you are only a guest. If you carefully contemplate the works of art in your body, in the hereafter you will have solved the riddle of the delicacies of those works. Of course, everyone’s time of death is unknown. Therefore, in this limited time, give your organs their due and give thanks to the God Almighty who gave you those gifts. Live according to His will, and always remember to glorify Him. Goodbye, Peter! May you and your troop be healthy!

Irfan Yilmaz is a professor of biology at Dokuz Eylul University, Izmir, Turkey