A Brief History of Veterinary Immunology

An awareness of the importance of the defense of the body against microbial invasion could not develop until the medical community accepted the concept of infectious disease. When infections such as smallpox or plague spread through early human societies, many people died, but some individuals recovered. It was rarely noticed that these recovered individuals remained healthy during subsequent outbreaks—a sign that they had developed immunity. Nevertheless, by the 12th century, the Chinese had observed that persons who recovered from smallpox were resistant to further attacks of this disease. Being practical people, they therefore deliberately infected infants with smallpox by inserting scabs from infected individuals into small cuts in their skin. Those infants who survived the resulting disease were protected from smallpox in later life. The risks inherent in this procedure were acceptable in an era of high infant mortality. On gaining experience with the technique it was found that using scabs from the mildest smallpox cases minimized the hazards. As a result, mortality due to smallpox inoculation (or variolation) dropped to about 1% compared with a mortality of about 20% in clinical smallpox cases. Knowledge of variolation spread westward to Europe by the early 18th century and was soon widely employed.

Outbreaks of rinderpest (then called cattle plague) had been a common occurrence throughout Western Europe since the ninth century and inevitably killed huge numbers of cattle. Since none of the traditional remedies appeared to work and the skin lesions in affected animals vaguely resembled those seen in smallpox, it was suggested in 1754 that inoculation might help. This process involved soaking a piece of string in the nasal discharge from an animal with rinderpest and then inserting the string into an incision in the dewlap of the animal to be protected. The resulting disease was usually milder than natural infection, and the inoculated animal became resistant to the disease. The process proved very popular, and skilled inoculators traveled throughout Europe inoculating cattle and branding them to show that they were protected against rinderpest (Box 1-1).

In 1798, Edward Jenner, an English physician, demonstrated that material from cowpox lesions could be substituted for smallpox in variolation. Since cowpox does not cause severe disease in humans, its use reduced the risks incurred by variolation to insignificant levels. The effectiveness of this procedure, called vaccination (vacca is Latin for “cow”) was such that it was eventually used in the 1970s to eradicate smallpox from the world.

Once the general principles of inoculation were accepted (even though nobody had the faintest idea how it worked), attempts were made to use similar procedures to prevent other animal diseases. Some of these techniques were effective. Thus, material derived from sheep pox was used to protect sheep in a process called ovination and was widely employed in Europe. Likewise, inoculation for bovine pleuropneumonia consisted of inserting a small piece of tissue from an infected lung into a cut in the tail. The tail fell off within a few weeks, but the animal became immune! Although the process was effective, infected material from the tail also spread the disease and delayed its eradication. On the other hand, administration of cowpox scabs to the nose of puppies to prevent canine distemper, although widely employed, was a complete failure.

The general implications of Jenner’s observations on cowpox and the importance of reducing the ability of an immunizing organism to cause disease were not realized until 1879. In that year, Louis Pasteur in France investigated fowl cholera, a disease caused by the bacterium now called Pasteurella multocida (Figure 1-1). Pasteur had a culture of this organism that was accidentally allowed to age on a laboratory bench while his assistant was on vacation. When the assistant returned and tried to infect chickens with this aged culture, the birds remained healthy (Figure 1-2). Saving money, Pasteur retained these chickens and subsequently used them for a second experiment in which they were challenged again, this time with a fresh culture of P. multocida known to be capable of killing chickens. To Pasteur’s surprise the birds were resistant to the infection and did not die. In a remarkable intellectual jump, Pasteur immediately recognized that this phenomenon was similar in principle to Jenner’s use of cowpox for vaccination. In vaccination, exposure of an animal to a strain of an organism that will not cause disease (an avirulent strain) can provoke an immune response. This immune response will protect the animal against a subsequent infection by a disease-producing (or virulent) strain of the same, or closely related, organism. Having established the general principle of vaccination, Pasteur first applied it to anthrax. He made anthrax bacteria (Bacillus anthracis) avirulent by growing them at an unusually high temperature. These attenuated organisms were then used as a vaccine to protect sheep against challenge with virulent anthrax bacteria. Pasteur subsequently developed a successful rabies vaccine by drying spinal cords taken from rabies-infected rabbits and using the dried cords as his vaccine material. The drying process effectively rendered the rabies virus avirulent (and probably killed much of it).

Although Louis Pasteur used only living organisms in his vaccines, it was not long before Daniel Salmon and Theobald Smith, working in the United States, demonstrated that dead organisms could make effective vaccines. They showed that a heat-killed culture of a bacterium called Salmonella choleraesuis (then called Bacillus suipestifer and believed to be the cause of hog cholera) could protect pigeons against the disease caused by that organism. A little later, Von Behring and Kitasato in Germany showed that filtrates taken from cultures of the tetanus bacillus (Clostridium tetani) could protect animals against tetanus even though they contained no bacteria. Thus bacterial products, in this case tetanus toxin, were also protective.

By 1900 many vaccines had been developed, and the development of immunity to infectious diseases of animals was a well-recognized phenomenon. Since then, immunologists have determined the molecular and cellular basis of this antimicrobial immunity. With this understanding has come the ability to use immune mechanisms to enhance resistance to infectious diseases. The role of the immune system in many different disease processes has been clarified. While much has been learned, much remains to be investigated. It is the current state of immunology as it relates to those species of interest to veterinarians that is the subject of this book.