Fighting Invaders

The immune systems of humans and horses are what keep us alive. Without a properly functioning immune system, disease would run rampant, with serious illness and death being the ultimate outcome. Unfortunately, it is not a simple system that functions the same for all species or even for all individuals within a species. Much of what we know about the immune system has been learned in recent years. There is promising research continuing, but generally speaking, progress is made in small stages or steps.

One of the most exciting approaches in ongoing research, says Johanna Watson, DVM, PhD, assistant clinical professor in the department of medicine and epidemiology at the University of California, Davis, involves determining the early responses of the immune system to disease. By understanding what is involved in the early response, researchers will be better able to come up with modalities of treatment and prevention, she believes. In other words, man will be able to do a better job of intervening and helping the equine immune system ward off attackers.

Watson describes the immune system and its role in preventing disease in terms of a battle against warring invaders. "Think of the body as the nation," she says, "and the immune system as the national defense."

Ian Tizard, PhD, BSc, BVMS, MRCVS, author of Veterinary Immunology, An Introduction, sees it in a similar light, though he uses a different analogy. "In some ways," he wrote, "the immune system
may be compared to a totalitarian state in which foreigners are expelled and citizens who behave themselves are tolerated, but those that 'deviate' are eliminated. While this analogy must not be pursued too far, it is apparent that such regimes possess a number of characteristic features.

"These include border defenses and a police force that keep the population under surveillance and promptly eliminate dissidents," he continued in his book. "Organizations of this type also tend to develop a pass system, so that foreigners not possessing certain identifying features are promptly identified and dealt with."

Watson, a researcher as well as an instructor at UC Davis, has this to say about the function of the immune system: "The immune system is a fascinating network of cells and cell 'depots.' This network not only protects the body from invaders like bacteria, viruses, and parasites, but it also travels long distances, communicates specifics regarding the enemy invader, and coordinates special forces to return to the front line. The immune system also keeps detailed records about all previous invaders for many years, allowing a very rapid response in case the same 'enemy' invades the body a second time."

The first line of defense, she explains in an article published in The Horse Report (a publication of the Center for Equine Health at UC Davis), is the innate immune system. It includes cells called macrophages (cells that engulf foreign bodies) and neutrophils (granulocytic white blood cells).

"The immune system," she explains, "sends information via macrophages to T and B lymphocytes, which are cells of the immune system that focus the response on the specific type of invader (i.e., bacteria, protozoa, virus). The T lymphocytes coordinate waves of T and B lymphocytes that are highly specific for the particular invader/pathogen. When the battle is over, memory T and B lymphocytes remain, containing all the information necessary to remount an effective response the next time the invader happens to gain access to the body. This specific response is called the adaptive immune response.

"There really is no other system that compares," Watson says. "Imagine that in order to evade a disease, you need to change the color of your eyes. That would require changing the genes that code for eye color in every cell in your iris. Sound impossible? Well, that is all in a day's work for the immune system. For each new disease agent or pathogen encountered, the immune system--T and B lymphocytes--rearranges its genes to accomplish a highly specific defense against the disease."

Vaccination and Immunity

The English word immunity has its roots in the Latin term immunis, which means exempt, explains Watson. A vague concept of immunity existed hundreds of years ago, but man's role in helping the body develop immunity was crude at best. There were those who realized that survivors of a disease rarely were afflicted with it again and attempted to build on this knowledge.

Listed by historians as being among the first to realize that disease survivors were not afflicted with the same malady a second time were the Chinese who lived many years before the birth of Christ. They had observed that individuals who recovered from smallpox were resistant to further attacks of this killing disease.

The Chinese attempted to apply this knowledge in a direct way. They deliberately infected infants with smallpox by rubbing the scabs from infected individuals into small cuts in the skin of those who had not contracted the disease. This "vaccination" procedure produced some dire consequences in the way of a high death rate among those treated. Then, the Chinese discovered that if they used material from individuals who had only a mild bout of smallpox, the mortality rate decreased dramatically. In fact, we are told, it dropped from 20% to 1% by using this approach.

History also reveals that back in 430 BC, Thucydides, the historian of the Peloponnesian War, wrote that only recovered plague victims should nurse the sick because they would not contract the disease.

Progress was made as time went on, but a landmark year for vaccine development was 1798, when English physician Edward Jenner discovered that material from cowpox lesions could be substituted for smallpox in inoculations against smallpox.

Of major concern to farmers in Europe during that time were periodic outbreaks of rinderpest or cattle plague, also referred to as cowpox. The skin lesions in affected cattle resembled those caused by smallpox in humans. It was felt in 1794 that perhaps cattle could be inoculated against the disease. The approach was a bit crude. A piece of string was soaked in the nasal discharge from an animal afflicted with rinderpest and the string was then inserted into an incision in the dewlap of the animal to be protected. The success rate was such that this method of inoculation gained acceptance, and "inoculators" traveled throughout Europe inoculating cattle against the virulent form of rinderpest.

Jenner then experimented with using material from cowpox to protect humans from smallpox, and the rest is history.

Another major step in the immunology field was taken by Louis Pasteur in 1879. It was something of an accidental breakthrough; Pasteur was studying the resistance of chickens to fowl cholera, a deadly bacteria-caused affliction. Pasteur had a culture of this organism that was accidentally allowed to "age" on a laboratory shelf while his assistant went on vacation. When the assistant returned, he attempted to infect the chickens with the aged culture. However, it no longer worked. The birds did not develop cholera. Later when the same chickens were infected with a fresh culture, it was discovered that they had become resistant to the disease. The chickens had been injected with a killed organism that was incapable of causing the disease, but at the same time it stimulated the immune system to react and protect the flock against future live invaders.

Pasteur was the first to refer to the process as vaccination. (Vacca is Latin for cow. Thus Pasteur's use of the terms vaccine and vaccination appear to be in honor of the work Jenner had carried out with cowpox.)

Pasteur's work also helped foster two terms that have become common in the field of immunology--virulent and avirulent. In vaccination, exposure of an animal to a strain of an organism that is incapable of causing the disease, but still invokes an immune response within the system, is known as avirulent. It protects the animal against future infections by a disease-producing (virulent) strain of the same or closely related organism.

"In the last 70 years," Watson reports, "scientists discovered most of what we know about the immune system. In the 1930s, researchers discovered antibodies, and in the 1950s, they determined that lymphocytes were the cells that govern the immune response. In the 1920s, scientists conducted early allergy studies, but IgE, the antibody responsible for allergic reactions, was not discovered until 1966."

As Watson noted, antibodies were discovered in the 1930s and knowledge about them and their role within the immune system has been invaluable. Antibodies are protein molecules produced by the plasma cells. Antibodies are found in many body fluids, but they are present in highest concentration in blood serum. They have the ability to bind specifically to an invading antigen (any foreign substance that stimulates an antibody response, such as a bacteria, virus, or parasite) and work to destroy it.

Researchers have used knowledge accumulated through the years in their attempt to better understand the immune system and prepare vaccines to protect against disease.

Immunity in the Young

Continued research also has revealed that some approaches in the past were incorrect. For example, W. David Wilson, MS, BVMS, MRCVS, a colleague of Watson's at UC Davis, has been heavily involved in research that indicates that an incorrect approach has been taken for years with foal vaccinations against such maladies as influenza and Western and Eastern equine encephalomyelitis.

Research has revealed that vaccinating before the foal reaches at least six months of age does more harm than good. This is because maternal antibodies passed on to the foal from the dam via colostrum inhibit the serologic response of foals to vaccination. (More on vaccinating young horses will be covered in the November installment of the vaccination series.)

Killed Vaccines

Through the years, researchers also have expanded on the work of Pasteur to produce safe vaccines by "killing" the disease-causing organism (as had happened with the organism involved with the aforementioned chickens), then using the killed entity to stimulate an immune response.

Pasteur, for example, developed a successful rabies vaccine by allowing spinal cords from rabies-infected rabbits to dry, then using the dry cords as his vaccine material. The drying process caused the virus from the infected rabbits to become avirulent (not disease-causing).

Today's scientists are adding still another exciting concept in vaccine development--bio-engineering with DNA material. Our current equine vaccines for West Nile virus (WNV) demonstrate the two approaches--one based on tried-and-tested theories over time and the other developed with newer bio-engineering techniques.

West Nile Innovator, the vaccine developed by Fort Dodge Animal Health, is a killed virus product. The manufacturer recommends two initial doses given intramuscularly three to six weeks apart, then annual booster vaccinations. Protection from the disease is reportedly achieved at least six weeks after the second initial dose. According to information in an Emerging Diseases paper published by the state of Michigan, the reported efficacy of the vaccine is 95%. In other words, 95% of properly vaccinated horses will be protected from disease if bitten by a mosquito carrying WNV.

A different approach to the development of a vaccine has been taken by Merial. Researchers with that company have developed a WNV vaccine known as Recombitek, which was approved for veterinary use by the USDA in 2004. This vaccine was developed through recombinant (the formation of new combinations of genes) DNA technology, and it has been proven to stimulate a protective immune response. Two initial doses four to six weeks apart are recommended by the manufacturer, as well as single annual booster shots.

Adding to the vaccines available against WNV, Fort Dodge Animal Health has recently submitted a WNV DNA vaccine for approval by the USDA (for more information, see "DNA Vaccine Awaits Approval" on p. 14).

More to Learn

While there has been progress in the field of immunology, Watson says, there still is much to be learned. Why, for example, are two animals afflicted with the same malady often affected differently? In one case, it might be a deadly illness, and in another, only a mild attack. What caused one immune system to be unable to ward off the disease and the other to at least partially protect against it? And why did the immune systems of other animals also exposed to the same disease totally fight off the attackers and allow those animals to remain healthy?

Watson says: "Immunology as a science has grown exponentially in the last 30 years, and there are many new tools available to study immune responses to different diseases in mice and humans. However, many of these tools are not available for the horse. In this century, the challenge for immunology researchers is to improve the science of vaccination and to develop immuno-therapeutic drugs to assist the body with a weak or inappropriate immune response. The challenge for those in equine immunology is to develop enough tools to do the same for the horse. Due to differences in their genes, people and animals respond differently to the same disease-causing pathogen. Once scientists can identify the genes responsible for these differences, then they can design therapies to help individuals with 'sub-standard' response to a given disease."

About the Author

Les Sellnow

Les Sellnow is a free-lance writer based near Riverton, Wyo. He specializes in articles on equine research, and operates a ranch where he raises horses and livestock. He has authored several fiction and non-fiction books, including Understanding Equine Lameness and Understanding The Young Horse, published by Eclipse Press and available at or by calling 800/582-5604.

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