Phagocytes and Lymphocytes​—The Big Guns!

But these are mere skirmishes compared to the battles that rage back and forth once alien organisms breach these outer defenses and enter the bloodstream and body tissues or fluids. They have invaded the territory of the big guns of the immune system​—the white blood cells, two trillion strong. Born in the bone marrow​—about a million every second—​they emerge to mature and form three distinct divisions: phagocytes and two kinds of lymphocytes, namely, T cells (three major kinds​—helper, suppressor, and killer cells) and B cells.

Now, the immune system may have a trillions-strong army, but each soldier can fight only one class of invader. During a disease millions of germs can be generated, and every one of those germs will have the same kind of antigen. But different diseases, even different varieties of the same disease, have different antigens. Before the T cells and the B cells can attack these invaders, they must have receptors that can bind to their particular antigens. Hence, among the T cells and the B cells, there must be many different receptors, receptors specific for the antigens of each and every different disease​—but each individual T cell and B cell has receptors that are specific for only one disease antigen.

Daniel E. Koshland, Jr., editor of the magazine Science, says on this point: “The immune system is designed to recognize foreign invaders. To do so it generates on the order of 10 ¹¹ (100,000,000,000) different kinds of immunological receptors so that no matter what the shape or form of the foreign invader there will be some complementary receptor to recognize it and effect its elimination.” (Science, June 15, 1990, page 1273) Thus, there are groups of T cells and B cells that, among them, can match every disease antigen that enters our body​—just as a key fits a lock.

To illustrate. Two locksmiths work completely independently of each other. One of them makes millions of locks of all kinds but no keys. The other makes millions of keys of all shapes but no locks. Now the billions of locks and keys are dumped into a giant container and shaken thoroughly, and every key finds a lock and fits itself into it. Impossible? A miracle? It would seem so.

Like locks with their keyholes, millions of germs with their antigens invade your body and circulate through your bloodstream and lymph system. Like millions of keys, your immune cells with their receptors also circulate there and fit onto the matching antigens of the germs. Impossible? A miracle? It would seem so. But the immune system accomplishes it nonetheless.

Each category of lymphocytes has its special role to play in the fight against infection. The helper T cells (one of the three major T cells) are crucial. They are the ones that orchestrate the various reactions of the immune system, directing the battle strategy. Triggered by the presence of enemy antigens, the helper T cells by chemical signals (proteins called lymphokines) rally the troops of the immune system and increase their ranks by the millions. Incidentally, it is the helper T cells that the AIDS virus singles out for attack. Once they are knocked out, the immune system is rendered virtually helpless, which leaves the AIDS victim vulnerable to all sorts of diseases.

At this time, however, consider the helper T cell’s role with the phagocytes, which are scavengers. Their name means “eating cells.” They are not choosy​—they eat anything that looks suspicious, whether foreign microorganisms, dead cells, or other debris. They function both as an army defending against disease germs and as a janitorial service gobbling up rubbish. They even eat the contaminants from cigarette smoke that blacken the lungs. If the smoking continues over a long period of time, the smoke destroys the phagocytes faster than they can be produced. Some of the meals of these eating cells, however, are indigestible, even fatal​—silica dust and asbestos fibers, for example.

Phagocytes are of two kinds, neutrophils and macrophages. The bone marrow pours out some one hundred billion neutrophils a day. They live only a few days, but during an infection, their numbers skyrocket, increasing fivefold. Each neutrophil may engulf and destroy up to 25 bacteria and then die, but replacements come in a steady stream. Macrophages, on the other hand, may destroy a hundred invaders before they expire. They are bigger, tougher, and live longer than the neutrophils. They respond in only one way both to invaders and to trash​—they eat them. It would be a mistake, however, to think of macrophages only as garbage disposal units. They “can manufacture as many as 50 different types of enzymes and antimicrobial agents” and function as communication links between “not only the cells of the immune system but also hormone-producing cells, nerve cells, even brain cells.”

Help! An Enemy Is in Our Midst!

When the macrophage ingests an enemy microorganism, it does more than just eat it. Like virtually all body cells, on its surface it carries the MHC molecules that identify it as self. But when the macrophage eats a germ, the MHC molecule draws out and displays a fragment of this enemy antigen in one of the grooves on its surface. This strip of antigen then acts as a red flag to the immune system, sounding the alarm that a foreign organism is on the loose inside of us.

By sounding this alarm, the macrophage is calling for reinforcements, more macrophages, millions of them! And this is where the helper T cell comes in. Billions of them are milling around in the body, but the macrophage must recruit a specific kind. It needs one with the kind of receptor that will fit onto the particular antigen that the macrophage is displaying.

Once this kind of helper T cell arrives and connects to the enemy antigen, macrophage and helper T cell exchange chemical signals. These hormonelike chemicals, or lymphokines, are extraordinary proteins that come with a bewildering array of functions to regulate and boost the immune system’s response to disease germs. The result is that both macrophage and helper T cell begin reproducing themselves prodigiously. This means more macrophages to eat more of the invading germs and more of the right kind of helper T cells to latch onto the antigens those macrophages will display. Thus the ranks of the immune forces explode, and hordes of these particular disease germs are vanquished.

T Cells and B Cells Go to College

THE T cells and the B cells can’t just come out of the bone marrow and go off to war. Their weaponry is ultramodern. High-tech training is mandatory before they take to the field. The T cells will be involved in biological warfare. B cells will be specializing in guided missiles. They get their training for this in the technical colleges of the immune system.

Hence, half of the millions of lymphocytes produced every minute in the bone marrow go to the thymus gland​—a small gland located behind the breastbone—​for their training as T cells. Concerning this, the book The Body Victorious says: “The lymphocytes which attend the technical college of the thymus are the helper, suppressor, and killer cells called T-lymphocytes (or T-cells). They are among the most indispensable armed forces of the immune system.”

Antibodies​—10,000 per Cell per Second!

The other “half of the unschooled lymphocytes,” The Body Victorious tells us, are B cells that go to the lymph nodes and related tissues for their training to be able to manufacture and launch guided missiles, called antibodies. When the B cells “muster in these tissues, they are like blank pages: they know nothing, and must learn from scratch” to “acquire the capacity to react specifically against substances foreign to the body.” In the lymph nodes, a mature B cell, activated by helper T cells and related antigen, “proliferates and differentiates to form plasma cells that secrete identical antibodies with a single specificity at a rate of about 10,000 molecules per cell per second.”​—Immunology.

To help us absorb the magnitude of what the immune system is accomplishing, an article in the National Geographic, June 1986, details the problem confronting the thymus gland: “Somehow, as the T cells mature in the thymus, one learns to recognize the antigens of, say, the hepatitis virus, another to identify a strain of flu antigens, a third to detect rhinovirus 14 [a cold virus], and so on.” After commenting on the “staggering task the thymus confronts,” the article says that in nature there are “antigens in hundreds of millions of different shapes. The thymus must turn out a group of T cells that recognizes each one. . . . The thymus pumps out T cells by the tens of millions. Even though only a few of them may recognize any one antigen, the collective scouting force is vast enough to identify the almost infinite variety of antigens nature produces.”

While some of the helper T cells were stimulating the macrophages to multiply, others in the lymph nodes were coupling with the B cells located there, causing them to multiply. Many of them become plasma cells. Again, there must be the right receptors on the helper T cells to join up with the B cells and cause them to produce plasma cells. It is those plasma cells that start churning out thousands of antibodies a second.

Since each plasma cell makes only one kind of antibody, with a receptor specific for only one disease antigen, soon billions are on the front lines homing in on the antigens of one specific disease. They latch onto the invaders, slowing them down, causing them to clump together, making them more tempting morsels for the phagocytes to gobble up. This, together with the release of certain chemicals by the T cells, whips up the macrophages into a feeding frenzy, causing them to gobble up millions of the invading microorganisms.

Moreover, the antibodies themselves can lead to the death of these microorganisms. Once they have locked onto its surface antigens, special protein molecules, called complement factors, flock onto the germ. When the required number of complement factors are in place, they penetrate the membrane of the microorganism, liquid flows in, and the cell bursts and dies.

These antibodies, of course, must also have the right receptors to latch onto the intruders. On this point the 1989 Medical and Health Annual of the Encyclopædia Britannica, page 278, says that B cells are able “to produce between 100 million and a billion different antibodies.”

Killer T Cells Wage Biological Warfare

By now the helper T cells have recruited millions of the scavenger macrophages to gobble up the enemy and have stimulated B cells with their antibodies to join the fray against the invaders, but there are still other forces that the helper T cells call to battle. They marshal millions of the deadliest fighters to join the struggle​—the killer T cells.

The goal of viruses, bacteria, and parasites is to get inside the body cells because once there, they are safe from the macrophages and the B cells and their antibodies​—but not from the killer T cells! One of these infected cells needs only to brush against a killer T cell to cause it to shoot the infected cell full of holes with lethal proteins, destroy its DNA, and spill its contents out in death. In this way killer T cells can attack and destroy even mutant cells and cells that have turned cancerous.

In addition to killer T cells, there are other killer cells in the immune system’s weaponry, namely, natural killer cells. Unlike T and B cells, these natural killer cells do not need to be triggered by a specific antigen. Cancer cells and cells invaded by other viruses are vulnerable to their onslaughts. But their reach may not be limited to viruses. Scientific American, January 1988, says that their “main targets are thought to be tumor cells, and perhaps also cells infected by agents other than viruses.”

How do these disease fighters meet up with the invading microorganisms? Is it just hit-or-miss? No. Nothing is left to chance. Disease antigens and T cells, B cells, phagocytes, and antibodies circulate throughout the body by means of the bloodstream and the lymphatic system. The secondary lymphoid organs, such as lymph nodes, spleen, tonsils, adenoids, patches of specialized tissue on the small intestine, and appendix, are sites where immune responses are initiated. The lymph nodes play a major role. Lymph is the fluid that bathes the cells in our tissues. It originates in those tissues, collects in thin-walled vessels and flows to the lymph nodes, continues throughout the rest of the lymphatic system, and finally completes its circulation by emptying into the large veins that lead into the heart.

As the disease antigens pass through the lymph nodes, they are filtered out and trapped. The disease fighters of the immune system take 24 hours to complete the entire lymphatic circuit, but 6 hours of that time is spent in the lymph nodes. There they meet the trapped invading antigens, and major battles begin. Likewise, enemy antigens traveling in the bloodstream do not escape. They are channeled to the spleen, where disease fighters are waiting to confront them.

Now the war within us is over. The invasion forces are defeated. The immune system with its trillion or more white blood cells has won. It’s time for another category of T cells to take over, namely, the suppressor T cells. When they see that the war has been won, they call off the battle and close down the fighting forces of the immune system.

Memory Cells and Immunity, With Complications

By this time, however, the B cells and the T cells have performed another vital service: They have produced memory cells that circulate in the bloodstream and the lymph vessels for many years​—in some cases for a lifetime. Should you ever be infected with the same strain of flu virus or cold virus, or with any other foreign substance encountered in the past, these memory cells will spot it immediately and rally the immune system for a quick and overwhelming assault. The memory cells will swiftly produce a flood of the specific type of B cells and T cells that fought off the first attack of this particular assailant. This new invasion is stamped out before it gains a foothold. What originally might have taken three weeks to defeat is now whipped before it gets started. Your previous infection by that particular invader has left you immune to it.

The picture is complicated, however, by the existence of different strains of flu viruses, often originating in different parts of the world. In addition, there are some 200 strains of cold virus, and each strain has its own particular antigen. So there must be 200 different types of helper T cells, each type having a receptor that matches the antigen of one of the 200 cold viruses. But that’s not all. The cold and flu viruses are constantly mutating, and each time that happens, there is a new cold or flu antigen that requires a new helper T-cell receptor to fit it. The cold virus keeps changing the locks, so the T cell must keep changing the keys.

Before you poke fun at doctors who can’t cure the common cold, understand the problem. The particular cold you have may be cured and never attack you again, but a newly mutated cold virus comes along, and your immune system must come up with an entirely new helper T cell to rally the immune forces to fight it. Win one battle, soon another begins. The war is endless.

Brain and Immune System Communicate

No wonder the immune system has been compared favorably with the brain. Research continues to show that it and the brain talk to each other about our health and that the mind exercises influence over the body, including the immune system. The following quotes indicate a relationship between brain and immune system. It’s a case of mind over body and body over mind.

“Immunologists are discovering more about the links between mind and body, the mechanisms of psychosomatic disease.”​—National Geographic, June 1986, page 733.

Recognized but little understood is the connection between the immune system and the brain. Mental stress, bereavement, loneliness, and depression affect the workings of the white blood cells, or lymphocytes, and this reduces T-cell activity. “The biological basis of these interconnections remains much of a mystery. It is clear, however, that the nervous and immune systems are inextricably linked, anatomically and chemically.”​—The Incredible Machine, pages 217, 219.

“The immune system . . . rivals the central nervous system in sensitivity, specificity, and complexity.”​—Immunology, page 283.

Science magazine reported on the link between the brain and the immune system: “A great deal of evidence shows that the two systems are inextricably interconnected. . . . The emerging picture shows that the immune and nervous systems are highly integrated, able to talk back and forth to coordinate their activities.”​—March 8, 1985, pages 1190-1192.

Defenders in the Ranks of the Immune System

1. Phagocytes Feeding cells, of two kinds: neutrophils and macrophages. Both are scavengers that consume inanimate trash, dead cells and other rubbish, and large numbers of invading microbes. Macrophages are bigger, tougher, stronger than the neutrophils, living longer and ingesting many more microorganisms. Much more than garbage disposal units, they manufacture different enzymes and antimicrobial agents, and they function as communication links between other cells of the immune system and even the brain.

2. MHC (major histocompatibility complex) Molecules on the surfaces of cells that identify the cells as a part of the body. On macrophages, the MHC displays a bit of the antigens of victims the macrophage has ingested, which stimulates both helper T cell and macrophage to multiply prodigiously to increase their ranks to battle with infection.

3. Helper T cells They are chiefs of operations of the immune system, identifying enemies and stimulating the production of other warriors of the immune system, rallying them to join battle with the invaders. They call up reinforcements in the ranks of macrophages, other T cells and B cells, and stimulate the production of plasma cells.

4. Lymphokines Hormonelike proteins, including interleukins and gamma interferon, by which immune cells communicate with one another. They activate many vital reactions of the immune system, thereby boosting its response to disease germs.

5. Killer T cells These T cells destroy cells in which viruses and microbes have hidden. They fire lethal proteins into these cells, punching holes in their membranes and causing the cells to rupture. They also eliminate cells that have turned cancerous.

6. B cells Under the stimulus of helper T cells, B cells increase in numbers, and some divide and mature into plasma cells.

7. Plasma cells These cells produce antibodies by the millions, which, like guided missiles, then circulate throughout the body.

8. Antibodies When antibodies come across antigens their receptors can latch onto, they grab them, slow them down, cause them to clump together to become tempting morsels for the phagocytes to gobble up. Or they do the job themselves, with the help of the complement factors.

9. Complement proteins Once the antibodies have locked onto the surface of the microorganism, proteins called complement flock onto it and inject liquid into it, causing it to burst and die.

10. Suppressor T cell When the infection is contained and the immune system has won, the suppressor T cells go into action and use chemical signals to halt the entire range of immune responses. The battle is won.

11. Memory cells By this time the T cells and the B cells have produced and left behind memory cells that circulate in the bloodstream and lymphatic system for years, even a lifetime. If another invasion is mounted by the same kind of organism that was previously defeated, an overwhelming attack is mounted by these memory cells, and this new invasion is quickly crushed. The body is now immune to that particular microorganism. This is the mechanism that makes vaccinations effective in eliminating diseases that were once scourges​—measles, smallpox, typhoid, diphtheria, and others.