8536d_ch01_001-0238/1/02 4: 25 PM Page 2 mac79 Mac 79: 45_BW: Goldsby et al./ Immunology 5e two thousand years passed before the concept was success- fully converted into medically effective practice The first recorded attempts to induce immunity deliber- ately were performed by the Chinese and Turks in the fif- teenth century. Various reports suggest that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin(a technique called variolation). In 1718, Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children. The method was significantly improved by the English physician Edward Jenner, in 1798. Intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subse quently immune to smallpox, which is a disfiguring and of- ten fatal disease, Jenner reasoned that introducing fluid from a cowpox pustule into people(i.e, inoculating them)might protect them from smallpox. To test this idea, he inoculated an eight-year-old boy with fluid from a cowpox pustule and later intentionally infected the child with smallpox. As pre lenner's technique of inoculating with cowpox to protect agal. for n knowledge of their causes, it was nearly a hun- against smallpox spread quickly throughout Europe. How- dred years before this technique was applied to other dis- ppens In sclence, ser ombination with astute observation led to the next major advance in immunology, the induction of immunity FICURE 1-1 Wood engraving of Louis Pasteur watching Joseph cholera. Louis Pasteur had succeeded in growing the bac- Meister receive the rabies vaccine. [From Harper's Weekly 29:836 terium thought to cause fowl cholera in culture and then had courtesy of the National Library of Medicine. J shown that chickens injected with the cultured bacterium de eloped cholera. After returning from a summer vacation, he injected some chickens with an old culture. The chickens be- 1885, Pasteur administered his first vaccine to a human,a came ill, but, to Pasteur's surprise, they recovered. Pasteur young boy who had been bitten repeatedly by a rabid dog then grew a fresh culture of the bacterium with the intention(Figure 1-1). The boy, Joseph Meister, was inoculated with a of injecting it into some fresh chickens. But, as the story goes, series of attenuated rabies virus preparations. He lived and his supply of chickens was limited, and therefore he used the later became a custodian at the Pasteur Institut. previously injected chickens. Again to his surprise, the chick- ens were completely protected from the disease. Pasteur Early Studies Revealed Humoral and Cellular hypothesized and proved that aging had weakened the viru- Components of the Immune System lence of the pathogen and that such an attenuated strain might be administered to protect against the disease. He Although Pasteur proved that vaccination worked, he did not called this attenuated strain a vaccine( from the Latin vacca, understand how. The experimental work of Emil von meaning"cow), in honor of Jenner's work with cowpox Behring and Shibasaburo Kitasato in 1890 gave the first in inoculation sights into the mechanism of immunity, earning von Behring Pasteur extended these findings to other diseases, demon- the Nobel prize in medicine in 1901 (Table 1-1). Von Behring strating that it was possible to attenuate, or weaken, a and Kitasato demonstrated that serum(the liquid, noncell pathogen and administer the attenuated strain as a vaccine. lar component of coagulated blood) from animals prevost In a now classic experiment at Pouilly-le-Fort in 1881, Pas- immunized to diphtheria could transfer the immune state teur first vaccinated one group of sheep with heat-attenuated unimmunized animals. In search of the protective agent, var- anthrax bacillus( Bacillus anthracis); he then challenged the ious researchers during the next decade demonstrated that vaccinated sheep and some unvaccinated sheep with a viru- an active component from imi erum could neutralize lent culture of the bacillus. All the vaccinated sheep lived, and toxins, precipitate toxins, and agglutinate(clump)bacteria all the unvaccinated animals died. These experiments In each case, the active agent was named for the activity it ex- marked the beginnings of the discipline of immunology. In hibited: antitoxin, precipitin, and agglutinin, respectivelytwo thousand years passed before the concept was success￾fully converted into medically effective practice. The first recorded attempts to induce immunity deliber￾ately were performed by the Chinese and Turks in the fif￾teenth century. Various reports suggest that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin (a technique called variolation). In 1718, Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children. The method was significantly improved by the English physician Edward Jenner, in 1798. Intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subse￾quently immune to smallpox, which is a disfiguring and of￾ten fatal disease, Jenner reasoned that introducing fluid from a cowpox pustule into people (i.e., inoculating them) might protect them from smallpox. To test this idea, he inoculated an eight-year-old boy with fluid from a cowpox pustule and later intentionally infected the child with smallpox. As pre￾dicted, the child did not develop smallpox. Jenner’s technique of inoculating with cowpox to protect against smallpox spread quickly throughout Europe. How￾ever, for many reasons, including a lack of obvious disease targets and knowledge of their causes, it was nearly a hun￾dred years before this technique was applied to other dis￾eases. As so often happens in science, serendipity in combination with astute observation led to the next major advance in immunology, the induction of immunity to cholera. Louis Pasteur had succeeded in growing the bac￾terium thought to cause fowl cholera in culture and then had shown that chickens injected with the cultured bacterium de￾veloped cholera. After returning from a summer vacation, he injected some chickens with an old culture. The chickens be￾came ill, but, to Pasteur’s surprise, they recovered. Pasteur then grew a fresh culture of the bacterium with the intention of injecting it into some fresh chickens. But, as the story goes, his supply of chickens was limited, and therefore he used the previously injected chickens. Again to his surprise, the chick￾ens were completely protected from the disease. Pasteur hypothesized and proved that aging had weakened the viru￾lence of the pathogen and that such an attenuated strain might be administered to protect against the disease. He called this attenuated strain a vaccine (from the Latin vacca, meaning “cow”), in honor of Jenner’s work with cowpox inoculation. Pasteur extended these findings to other diseases, demon￾strating that it was possible to attenuate, or weaken, a pathogen and administer the attenuated strain as a vaccine. In a now classic experiment at Pouilly-le-Fort in 1881, Pas￾teur first vaccinated one group of sheep with heat-attenuated anthrax bacillus (Bacillus anthracis); he then challenged the vaccinated sheep and some unvaccinated sheep with a viru￾lent culture of the bacillus. All the vaccinated sheep lived, and all the unvaccinated animals died. These experiments marked the beginnings of the discipline of immunology. In 1885, Pasteur administered his first vaccine to a human, a young boy who had been bitten repeatedly by a rabid dog (Figure 1-1). The boy, Joseph Meister, was inoculated with a series of attenuated rabies virus preparations. He lived and later became a custodian at the Pasteur Institute. Early Studies Revealed Humoral and Cellular Components of the Immune System Although Pasteur proved that vaccination worked, he did not understand how. The experimental work of Emil von Behring and Shibasaburo Kitasato in 1890 gave the first in￾sights into the mechanism of immunity, earning von Behring the Nobel prize in medicine in 1901 (Table 1-1). Von Behring and Kitasato demonstrated that serum (the liquid, noncellu￾lar component of coagulated blood) from animals previously immunized to diphtheria could transfer the immune state to unimmunized animals. In search of the protective agent, var￾ious researchers during the next decade demonstrated that an active component from immune serum could neutralize toxins, precipitate toxins, and agglutinate (clump) bacteria. In each case, the active agent was named for the activity it ex￾hibited: antitoxin, precipitin, and agglutinin, respectively. 2 PART I Introduction FIGURE 1-1 Wood engraving of Louis Pasteur watching Joseph Meister receive the rabies vaccine. [From Harper’s Weekly 29:836; courtesy of the National Library of Medicine.] 8536d_ch01_001-023 8/1/02 4:25 PM Page 2 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: