How The Body’s Defences Tell Friend From Foe

Press, Volume CIX, Issue 31985, 12 May 1969, Page 9

How The Body’s Defences Tell Friend From Foe

WALTZR SULLIVAN)

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The fact that man can develop within his body the means to fight off disease was probably well known long before the birth of medicine as a science. In particular it was recognised that persons who had once overcome a disease, such as smallpox or the plague, would not suffer from it again. It was not until the discovery that bacteria can cause disease and that blood serum is responsible for immunity, however, that progress toward an understanding of the immune reaction became passible. Blood serum is the clear fraction of the blood that remains when the red portion dots. It is rich in large protein molecules known as immunoglobulins which, it is now known, serve as the body’s defenders against intrusion, whether by bacteria, viruses or foreign tissue, such as transplanted organs. Peculiar To Vertebrates Each of these immunoglobulins, known also as “antibodies,” carries structural “pinchers” capable of seizing only one particular kind of invading molecule. Hence an enormous variety

of antibody designs is needed for the protection of an individual.

This immunity system is pecular to the vertebrates. None of the lower forms of life has it and therefore it is comparatively easy, Tor example, to transplant tissues from one Insect to another.

One of the most challenging problems in modern biology is to find out how and why the body recognises and destroys foreign tissues, even if they come from a close relative, and yet it does not normally fight its own tissues. When it does so, in the so-called autoimmune diseases, the effects can be disastrous.

A major step toward an understanding of these problems was reported in April. Dr Gerald M. Edelman of Rockefeller University described the first complete decipherment of an immunoglobulin molecule. The scope of that feat is evident when one compares the complexity of this molecule with that of

the largest one previously deciphered. The latter, the molecule of subtilisin, is formed of 274 amino acids whereas the immunoglobulin molecule deciphered at Rockerfeller University contains 1320 such building blocks—-a total of 19,996 atoms. Exposing Clues The determination of the amino .acid sequence has shown where, along the four

1 constituent, chains of the i molecule, there are the sulfide bonds that hold the s assemblage in its three- . dimensional form, ready to f capture an invader. The exact t nature of that form cannot rbe determined until an s immunoglobulin has been crytalised and subjected to • X-ray analysis. t Dr Edelman presented his f results to the Federation of I American Societies for Ex- , perimental Biology in Atlantic i City. With one immunos globulin deciphered it is now i possible to examine others, i spelling out their differences i and similarities and hence i exposing clues to the way in which they work. i Only with such knowledge • .will it be possible to explain . the mysterious process that ! tells the body’s defensive ■ system which is friend and ! which is foe. That achieved, it • should be possible to devise I ways to manipulate that i system, persuading the body’s ' defences that a heart taken ! from someone else (or from ’ an animal, such as a pig) is a friend. f J Inducing Tolerance The latest findings regard- , ing immunity and what proi duces tolerance towards one’s ! own tissue were described at an international conference held last September at Brook Lodge in Atlanta, Michigan. Its proceedings have been i circulated in recent days. ‘ It appears that the cells ■ within the body that produce " antibodies when “turned on” ■by encountering an invader belong to the same family as cells that are “turned off” by the procedure that makes the ’ body tolerant to its own tissues.

Further, its has been found that under certain circumstances it is possible to induce tolerance to an invader. This remarkable—and still perplex-ing-discovery regarding the development of tolerance was made in Britain several years ago. When very small or very large amounts of a foreign material are injected into an animal, a tolerance for the material develops. With small amounts, however, the effect is too slow to appear very promising as a way to outwit the body’s defences. In the case of large amounts, the animal not only tolerates the invader, but acquires a lifelong tolerance to it Small Pieces Yet for some reason that may ultimately help resolve the mystery, the injected material produces tolerance

only when broken up into small bits (presumably individual molecules). Thus, if such material has been filtered, it will induce tolerance. Otherwise it may be rejected. There is now a suspicion that exposure to massive doses is how the body becomes tolerant to its own tissues. When the immune system first goes into action, during the organism’s infancy, it is exposed to massive quantities of all the materials forming the body. In some way this turns off (or, some believe, kills) the millions or billions of cells capable of making antibodies designed to attack each such substance. In theory, If one could extract heart tissue from a potential donor, culture it to massive proportions in the laboratory and inject material extracted from it into the intended recipient, the latter would become tolerant to the heart, but this hardly seems practical at this time. Nevertheless, some sort of manipulation of the immune system may some day become possible.

Likewise an understanding of autoimmune disease may come within reach. One of the most often cited is rheumatoid arthritis, but there are many others. One whose cause is believed to be known is called sympathetic ophthalmia. Ultimate Hope 'lt arises from a blow or other injury that damages the uvea, or middle coating, of the eye. Not only is that eye affected, but, if there is not suitable treatment, the other eye may gradually lose its sight. The reason, apparently, is that the injury exposes the body’s defence system to substances that hitherto were Isolated within the eye. As a result, the body regards the eye material as foreign and both eyes are destroyed. In another such disease, "acquired haemolytic anaemia,” the body begins to attack its own red blood cells, either because they have changed their chemical configuration in some subtle way, or because the defence system somehow has “forgotten” that the material of the red cells is “friendly.” The ultimate hope of those studying the immune system is not only to teach it to tolerate desirable “foreigners” but to reject “natives” that have become hostile—namely the proliferating cells of cancer. Copyright. “New York Times” News Service.