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Applications of Immune Responses

I / accination, the practice of deliberately stimulating the MX immune system in order to protect individuals against a disease, has become routine all over the world. As a result, many of the diseases that once caused widespread death and disability, such as smallpox, measles, whooping cough, mumps, and poliomyelitis, are now non-existent or much less common.

Even before people knew that microorganisms caused disease, it was recognized that individuals who recovered from a disease such as smallpox rarely contracted it a second time. Old Chinese writings dating from the Sung dynasty (a.d. 960-1280) describe a procedure known as variolation, in which small amounts of the powdered crusts of smallpox pustules were inhaled or placed into a scratch made in the skin. Usually the resulting disease was mild, and a permanent immunity to smallpox resulted. Occasionally, however, severe disease developed, often resulting in death. Nevertheless, the risk of serious disease using this procedure was rare enough that people were willing to take the risk.

Although variolation was practiced in China and the Mideast a thousand years ago, it was not widely used in Europe until after 1719. At that time, Lady Mary Wortley Montagu, wife of the British ambassador to Turkey, had their children immunized against smallpox in this way. Since smallpox was disfiguring, producing deep scars ("pocks"), and was often fatal, variolation subsequently became popular in Europe.

Although a person exposed to smallpox through variolation would usually completely recover and so was not at great risk, he or she would become contagious. Because of the danger of contagion and because the procedure was reasonably expensive, large segments of the population in Europe remained unprotected.

As an apprentice physician, Edward Jenner noted that milkmaids who had suffered cowpox infections rarely got smallpox. Cowpox was a disease of cows that caused few or no symptoms in humans. In 1796, long before bacteria and viruses had been discovered, Jenner conducted a classic experiment in which he deliberately transferred material from a cowpox lesion on the hand of a milkmaid, Sarah Nelmes, to a scratch on the arm of a young boy named James Phipps. Six weeks later, when exposed to pus from a smallpox victim, Phipps did not develop the disease. The boy had been made immune to smallpox when he was inoculated with pus from the cowpox lesion. Using the less dangerous cowpox material in place of the pustules from smallpox cases Jenner and others worked to spread the practice of variolation. Later, Pasteur used the word vaccination (from the Latin vacca for "cow") to describe any type of protective inoculation. By the twentieth century, most of the industrialized world was generally free of smallpox as the result of routine vaccination of large populations.

In 1967, the World Health Organization (WHO) initiated a program of intensive smallpox vaccination. Since there were no animal hosts and no non-immune humans to whom it could be spread, the disease died out. The last case of naturally contracted smallpox occurred in Somalia, Africa, in 1977. In 1979 in a ceremony in Nairobi, Kenya, WHO declared the world free of smallpox. Nevertheless, a few laboratories around the world still have the virus. In this age of bioterrorism concerns, some see smallpox as a major threat should the deadly virus ever be released into the largely unprotected populations of the world. Because of this, vaccine stores in the US are being increased.

It is now known that the smallpox and cowpox viruses are closely related. The vaccinia virus used in recent years for vaccination against smallpox is neither the cowpox nor the smallpox virus, and it is not clear where this virus originated. Some scientists believe that the vaccinia virus is a hybrid of the cowpox and smallpox viruses. Quite possibly it developed during Jenner's time, when calves injected with cowpox virus to produce vaccine material accidentally received the smallpox virus at the same time. In addition to its importance in defeating smallpox, the vaccinia

420 Chapter 17 Applications of Immune Responses virus has been genetically engineered in recent years to make experimental vaccines against other diseases such as AIDS and viral hepatitis. Thus, Edward Jenner's legacy extends beyond the eradication of smallpox.

—A Glimpse of History

IN CHAPTERS 15 AND 16, WE DISCUSSED BASIC defense mechanisms, both innate and adaptive, and became acquainted with antibodies and lymphocytes. This chapter will consider how immunization can be used to enhance the immune response and how immunization techniques have advanced remarkably in recent years to become safer and more effective. In fact, immunization has had probably the greatest impact on human health of any medical procedure, and we shall see that even better means of immunization are likely in the near future. We will also explore some useful applications of immunological reactions in diagnostic tests.

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