Our Immune System​—A Miracle of Creation

We cannot see them, but they are there. Their teeming millions are everywhere around us, clinging to us, bent on getting inside of us. They crave the moist, nutritional warmth within us, and once there, their numbers escalate alarmingly. If left uninhibited, they would soon take us over completely. Our only response to counter this destructive force is war, a war within us. It must be instant and total war between these disease-carrying alien invaders and our body’s immune system with its two trillion defenders.a No quarter asked, none given. Our lives hang in the balance. It’s them or us. Usually we win. But not always. The outcome depends on how quickly and completely our immune system gears up for the fight.

THE immune system is one of the most incredible and complex features of our amazingly and wonderfully made bodies. It is compared favorably with the most complex organ of them all, the human brain. Immunologist William Paul of the National Institutes of Health says: “The immune system has a phenomenal ability for dealing with information, for learning and memory, for creating and storing and using information.” High praise, but not too high. Dr. Stephen Sherwin, director of clinical research at Genentech, Inc., adds his tribute: “It’s an incredible system. It recognizes molecules that have never been in the body before. It can differentiate between what belongs there and what doesn’t.” And if it doesn’t, it’s war!

How does our immune system know what belongs there and what doesn’t? A special protein molecule, called MHC (major histocompatibility complex), sits on the surface of nearly every cell of our body. It is an identity tag that tells the immune system that this cell is a friend, a part of us, unique to us. The immune system thereby recognizes our own cells and accepts them but attacks any cells displaying different molecules on their surfaces​—and all cells not ours do display surface molecules different from ours.

So it is by means of these surface molecules that our immune system recognizes each cell as “us” or “them,” as self or nonself. If nonself, it triggers a reaction by our immune system. “The concept that the immune system must discriminate continually between self and nonself,” says the book Immunology, “is a cornerstone of all immunological theory.” In the category of nonself are such disease-causing organisms as viruses, parasites, fungi, and bacteria.

The Skin​—More Than a Passive Covering

The skin is the first line of defense against these foreign invaders. More than just a passive protective covering, it has cells that warn the immune system of invading microorganisms. Billions of friendly bacteria live on the skin​—in some places nearly 20 million per square inch [3 million per sq cm]. Certain ones produce fatty acids that hinder growth of harmful kinds of bacteria and fungi. Scientific American, June 1985, calls the skin an “active element of the immune system,” with specialized cells that “have interacting roles in the response to foreign invaders.”

Joining the skin as a part of the body’s protective covering are the membranes that line the internal surfaces of the body. These membranes secrete mucus that traps microbes. Saliva, nasal secretions, and tears contain microbe-killing substances. Hairlike cilia in the air passages leading to the lungs push mucus and debris into the throat, where they can be eliminated by sneezing and coughing. If any invaders reach the stomach, they are either killed by the acids there, broken down by digestive enzymes, or trapped in the mucus that lines the stomach and the intestines. Eventually, they are evacuated along with other body waste.

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.

[Footnotes]

[Box on page 4, 5]

“Prefabricated Weapons Against Every Conceivable Invader”

The immune system maintains “an armory of prefabricated weapons against every conceivable invader.” This profusion of weaponry “is known to be produced by a complex genetic process in which parts of genes are shuffled and recombined.” Now the report of a recent major discovery sheds light on how this happens.

“The newly discovered gene is believed to play an important role in that genetic recombination process. The scientists have named the gene RAG-1 for recombination activating gene.” That discovery was reported in the magazine Cell, December 22, 1989. But the scientists at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, U.S.A., who discovered RAG-1, worried that “the recombination gene was too inefficient and slow to explain how the body produces such a steady and dazzling variety of immune proteins. To meet the possibility of any sort of invasion, the body must keep on tap many millions of antibodies and T-cell receptors, all shaped just differently enough that at least a few can recognize even an entirely new type of pathogen.”​—The New York Times, June 26, 1990.

So these same scientists began looking for another gene to overcome this difficulty. Six months later Science magazine of June 22, 1990, reported that they had found it. “The scientists say the new gene, RAG-2, works with the first gene to weave together antibodies and receptor proteins more speedily. When operating in tandem, the two genes can recombine pieces of the immune system from 1,000 to one million times more efficiently than either gene can independently.” Working in tandem, RAG-1 and RAG-2 pour out the millions of antibodies and T-cell receptors needed.

This research is described as “a very elegant piece of science.” It is a major discovery that may open the door to a better understanding of some genetic diseases in which the body’s defense systems fail.​—The New York Times, December 22, 1989.