Vaccines are designed based on the specific nature of an antibody response to an antigen. In other words, the antibody will work only against the antigen that stimulated its production. A "booster" creates more antibodies, a quicker response, and longer protection.
The equine immune system, which is designed to protect a horse from invading pathogens, is extremely complex. When everything is functioning in synchrony, the system works well. The problem is that many things can compromise the immune system, and when that happens, the horse is at an increased risk of developing disease. Often one (or more) of three key elements are at the root of the problem when the immune system becomes compromised, says Glen Gamble, DVM, of Riverton, Wyo. They are stress, nutrition, and age.
When a horse is stressed, lacking in proper nutrients, or old, he says, the immune system can't function appropriately and pathogens are able to breach the defensive lines. But before we can understand how that works, we must first understand the immune system.
One of the most interesting descriptions of an animal's immune system is provided by Ian Tizard, PhD, BSc, BVMS, MRCVS, who authored the book, Veterinary Immunology, An Introduction.
"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 who '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 keeps the population under surveillance and promptly eliminates dissidents. 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."
Fighting the Invaders
Who are these foreigners and how are they dealt with? A term for the foreigners is antigen. Simply put, an antigen is any foreign substance that stimulates an antibody response. (Antibodies are specific proteins that are produced to engage in combat against specific antigens and eliminate them.) Antigens include x bacteria, viruses, and parasites.
First, of course, the system must recognize that it is under attack and identify the attacker. This is like a sentry discovering an intruder and sounding the alarm. Once that recognition occurs, the immune system launches a counter-attack either via the antibody-forming system or the cell-mediated system, both of which will be discussed in more detail shortly. It is up to these systems to come up with the appropriate weapons through the production of specific antibodies or cells that are capable of eliminating the antigens.
Another important component is important in the aftermath of battle--memory.
"The immune system must also remember this event," Tizard reports, "so that on subsequent exposure to the same antigen, its response will be faster and more efficient. In our totalitarian state analogy, the information will be filed away for future use."
The basic requirements of an immune system, according to Tizard, include four components:
A method of trapping and processing antigens;
A mechanism for reacting specifically to the specific antigen (becoming antigen-sensitive);
Cells to produce antibodies or to participate in the cell-mediated immune response; and
Cells to retain memory of the event and to react specifically to the antigen in future encounters.
"All of these components can be recognized within the body," according to Tizard, "and each is associated with a specific type of cell. Antigens are trapped, processed, and eventually eliminated by cells known as macrophages. Lymphocytes (cells that originate from stem cells and differentiate in lymphoid tissue such as the thymus or bone marrow) also function as memory cells and therefore initiate a secondary immune response. The cells that mediate the cell-mediated responses are also identified as lymphocytes (more on this later), while antibody-producing cells are derived from lymphocytes and are known as plasma cells."
The complexity of a horse's immune response is underscored by the fact that his body is faced with the task of permitting the free access of necessary nutrients and oxygen, while at the same time excluding potentially dangerous organisms, such as bacteria, parasites, and viruses.
Another challenge is that if the body is going to reject foreign invaders, it must tolerate or recognize its own cells as being "not-foreign." If such recognition does not occur, the animal will suffer from autoimmune disease, which means that antibodies or lymphocytes destroy normal cells in an effort to eliminate the "offending" antigen.
With Tizard as our chief guide, along with other researchers in the field, we will take a tour of the horse's immune system. When that is concluded we will address the matter of vaccination and the latest information concerning its effects on the immune system of the equine at certain early stages of life.
We also will take a look at how stress, nutrition, and age can impact the immune system.
The horse's defense mechanisms begin at the skin, which when unbroken helps keep pathogens from invading underlying tissues. Defenses that are designed to trap--then eliminate--any foreign material that succeeds in breaching the outer defenses also are found within the body.
The trapping system within the body features cells able to bind, ingest, and destroy foreign material through a process known as phagocytosis, which simply means that the phagocytes "eat" the invading agents.
There are two systems directly involved in the production of these phagocytic cells within the horse. One is called the myeloid system, which consists of cells that act rapidly, but are incapable of sustained effort. The other system is called the mononuclear phagocyte system, which consists of cells that act more slowly, but are capable of repeated phagocytosis.
The major cell type in the myeloid system is the neutrophil, which is formed in the bone marrow and migrates to the bloodstream. Neutrophils remain in the bloodstream for about 12 hours, then move into the tissues. Their total life-span is only a few days, but new neutrophils are constantly being formed in the bone marrow.
Phagocytosis is the major function of a neutrophil. Because of its structure and nature of attack, the neutrophil is considered the first line of defense for the immune system. The problem is that neutrophils possess a limited reserve of energy that cannot be replenished. This means that when neutrophils are first released from bone marrow, they are capable of a burst of energy in the early going (sort of like a short-distance sprinter), but quite rapidly become exhausted and normally are capable of undertaking only a limited number of phagocytic events.
There are two other cells to be identified before leaving a discussion of the myeloid system--eosinophils and basophils. Eosinophils develop within the bone marrow and migrate into the bloodstream to ultimately take up residence in the tissues. One of their key functions is to kill parasitic larvae. Basophils are the least numerous of the myeloid cells--their basic purpose is to provoke an inflammatory response where antigens are deposited.
Because the neutrophils of the myeloid system are unable to mount a sustained attack, a second line of defense is needed. It is provided by the mononuclear phagocyte system. This system consists of cells called macrophages. Unlike neutrophils, macrophages are capable of sustained phagocytic ability (more like a distance runner). Another of their jobs involves repairing tissue damage by removing dead, dying, and damaged tissue.
Macrophages are widely distributed throughout the body. In addition to being phagocytic, macrophages secrete factors that help cause fever. Fever is a part of the overall defense system--it promotes defensive cell proliferation. It also induces lethargy that reduces the horse's activity level and thus his energy demands, enhancing the efficiency of defense and repair mechanisms.
Macrophages also help produce inflammation and process foreign material so that an immune response is provoked.
Inflammation is the response of tissues to irritation or injury. It serves as a protective mechanism since it provides a means by which defensive cells that are normally confined to the bloodstream can gain direct access to sites of microbial invasion or tissue damage.
Next, we turn our attention to antibodies. These protein molecules are produced by the plasma cells, and they have the ability to bind specifically to antigens and hasten their destruction or elimination. Once bound together, the antigen can then more easily be engulfed by a phagocyte. This system enhances the efficiency of antigen destruction.
Antibodies are found in many body fluids, but are present in highest concentration in blood serum (a liquid part of blood remaining after cells and clotting factors have been removed). Antibodies are classified as globulins, and are generally known as immunoglobulins (Ig). The term immunoglobulin is used to describe all proteins with antibody activity as well as some proteins that have the characteristic molecular structure of antibody molecules, but have no known antibody activity.
Immunoglobulin G (IgG) is the one found in highest concentration in serum. When observed under an electron microscope, the molecule seems Y-shaped. The "arms" of the Y are capable of binding antigens. The site on an antigen molecule that stimulates an immune response from an antibody and is the site for binding to an antibody is called the epitope, or antigenic determinant.
Gentlemen, Start Your Engines!
Now for a look at the immune response. The mounting of an immune response in a horse's system is the job of lymphocytes; these small round cells are the predominant cell type in organs such as the spleen, lymph nodes, and thymus.
The organs whose function is to regulate the production and differentiation of lymphocytes are known as the primary lymphoid organs; these include the thymus and Peyer's patches in horses and other mammals.
The thymus is an organ found within the mass of tissues and organs separating the lungs. In horses, it also extends up the neck as far as the thyroid gland. The thymus reaches its maximum weight and size at puberty, then undergoes involution (shrinking or return to a former size). It's necessary in early life for development and maturation of cell-mediated immunological functions.
Tizard explains the functions of the thymus by describing what occurs when it is surgically removed from young rodents:
"Thymectomy performed on mice within a day of birth results in these animals becoming much more susceptible to infection and occasionally failing to grow. Examination of these neonatally thymectomized animals reveals that they have greatly reduced numbers of circulating lymphocytes and their ability to mount some type of immune response is impaired. In particular, their ability to reject grafts is severely compromised, reflecting a total loss of the cell-mediated immune response. Antibody-mediated immunity is also depressed, but to a lesser extent."
However, Tizard reports, removal of x the thymus from domestic animals such as the horse yields much less dramatic results. This, he states, is because the thymus matures earlier in these species and has performed many of its critical tasks well before the animal is born. Removal of the thymus of adult animals has little effect on the immune system, according to Tizard.
Next we take a look at Peyer's patches. In the newborn foal, the lymphoid tissue of the intestine consists of clusters of lymphocytes and macrophages within the mucosa. These clusters are overlaid by epithelium that is thin and consists of specialized cells called M cells. The M cells transport antigens from the intestinal lumen into the underlying lymphoid tissues where they can be destroyed. Under the influence of antigens, the lymphoid tissue expands to form Peyer's patches, which help regulate and differentiate lymphocytes.
Lymphocytes are divided into two identities--B cells and T cells. The two cell types play different roles. B cells are thymus-independent, migrating to the tissues without passing through or being influenced by the thymus. They play a major role in humoral (found in body fluids) immunity. When stimulated by an antigen, they mature into plasma cells that synthesize humoral antibody.
T cells are thymus-dependent--they either pass through the thymus or are influenced by it as they travel toward the tissues. They can kill such cells as tumor and transplant tissue cells. T cells are largely responsible for cell-mediated immunity.
Along with the two primary lymphoid organs, there are also secondary lymphoid organs, including the lymph nodes, spleen, and lymphoid nodules of the gastrointestinal, respiratory, and urogenital tracts.
These organs are rich in macrophages and dendritic cells (similar to a macrophage, but not as capable of phagocytosis) that trap and process antigens, and they are rich in T and B lymphocytes.
Lymph nodes--These round or bean-shaped structures are strategically placed on lymphatic channels in such a way that they can trap antigens being carried through the lymph, which is a transparent, slightly yellow liquid found in lymphatic vessels and derived from tissue fluid. In essence, lymph nodes filter antigens from lymph fluid.
Spleen--Just as lymph nodes filter antigens from lymph, the spleen filters antigens from blood. This filtering process removes both antigenic particles and aged blood cells. (Interestingly, not only antigens are trapped by the spleen and lymph nodes. Lymphocytes that normally pass freely through these organs also are trapped in the presence of antigens. Trapping serves to concentrate lymphocytes in close proximity to sites of an antigen accumulation and, thus, enhances the efficiency of the immune response.)
Secondary lymphoid tissues--Antibodies are produced in the secondary lymphoid tissues. These tissues include bone marrow and lymphoid tissues scattered throughout the body.
Recruiting Soldiers in Peacetime
The above description of the horse's immune system is basic, to say the least. However, it sets the stage for the next part of the discussion, which concerns vaccination to establish immunity from certain diseases.
Simply put, vaccination involves a person administering to the horse an antigen derived from an infectious agent so that an immune response is mounted and resistance to that infectious agent is achieved. There have been interesting strides made in the development of immunizing agents, and there have also been changes in thinking about certain vaccination protocols.
First, a bit of history so we can better understand how the vaccination process came into being at a time when information on the immune system was far less advanced than it is today. In the years before vaccinations became commonplace, one either survived when disease struck or one didn't. Little notice was paid to the fact that the survivors almost never were afflicted with the same disease again.
Among the first to realize that disease survivors were generally not afflicted with the same malady a second time were the early Chinese, dating to 2650 BC. They observed that individuals who recovered from smallpox were resistant to further attacks of this deadly disease.
The Chinese took a direct approach in implementing what they had observed. They deliberately infected infants with smallpox by rubbing the scabs from infected individuals into small cuts in their skin. This "vaccination" procedure had some dire consequences in the form of a high rate of infant mortality. However, in those days, the risks were accepted because infant mortality was high anyway.
Then, the Chinese discovered that if they used material from individuals who had only a mild bout of smallpox, the mortality rate was lessened. In fact, the mortality rate dropped from 20% to 1% by using this approach. Knowledge of this inoculation procedure spread westward to Europe in the early 18th Century, and it soon came to be widely employed.
Major concerns to farmers in Europe during that period were periodic outbreaks of rinderpest or cattle plague. The skin lesions in affected cattle resembled those caused by smallpox in humans.
It was suggested in 1754 that inoculation might help prevent the disease. The approach was somewhat 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 resulting disease was usually milder than that from natural infection. Before long inoculators were traveling all through Europe inoculating cattle against the more virulent form of rinderpest.
A major breakthrough that has been of great benefit to humans occurred in the same century. In 1798, Edward Jenner, an English physician, discovered that material from cowpox lesions could be substituted for smallpox in inoculations against the disease. Cowpox doesn't cause severe disease in humans, so its use reduced the risks incurred in protecting against smallpox.
Louis Pasteur in 1879 underscored the importance of reducing the ability of an immunizing organism to cause disease. And it all came about by accident--Pasteur was studying the resistance of chickens to fowl cholera, a deadly bacterial affliction. One of his cultures of this organism 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, the birds did not develop cholera.
Later, when the same chickens were injected with a fresh culture, it was discovered that they had become resistant to the disease. Pasteur recognized that this phenomenon was similar in principle to Jenner's use of cowpox. He was the first to refer to the process as vaccination. (Vacca is Latin for cow.)
Two more terms as they relate to the immune system must be added to the vocabulary at this point--avirulent and virulent. In vaccination, exposure of an animal to a strain of an organism that will not cause disease (avirulent strain) can invoke an immune response that protects the animal against infection with a disease-producing (virulent) strain of the same, or a closely related, organism.
Pasteur first applied this "new" principle to anthrax. He rendered anthrax bacteria avirulent by growing them at unusually high temperatures. It worked--the avirulent strain protected test sheep from anthrax without first causing the disease.
Pasteur also developed a successful rabies vaccine by allowing spinal cords from rabies-infected rabbits to dry, then using the dried cords as his vaccine material. The drying process rendered the rabies virus avirulent. Later, research revealed that steps could be taken to "kill" the disease-causing organisms and still use them effectively to induce immunity in patients.
It was also learned that the substances that provided disease resistance could be found in blood serum. For example, if serum obtained from a horse which was vaccinated against tetanus toxin is injected into a normal horse, the normal horse will become resistant to tetanus for a short period of time. Serum derived from an immune horse in this way is known as tetanus immune globulin or tetanus antitoxin, and it is used today in the prevention of tetanus.
How Vaccines Work
Vaccines are designed based on the specific nature of an antibody response to an antigen. In other words, the antibody will work only against the antigen that stimulated its production. Vaccinating a horse against tetanus, for example, will provide no protection against any other malady or disease. The protection is only against tetanus.
In many equine vaccination programs, horse owners are encouraged by their veterinarians to give a "booster" shot, or shots, in the wake of the primary inoculation. The second injection of an antigen is very different from the first in that response occurs much more quickly, antibodies are produced in greater number, and the protection lasts much longer.
x Vaccinating foals might be more complicated than previously realized. For example, researchers have just recently come to grips with the fact that seeking to bolster a horse's immune system against certain diseases early in life can actually have the opposite effect.
A case in point involves vaccinating foals against such diseases as influenza, Eastern and Western equine encephalomyelitis, and equine herpesvirus types 1 (EHV-1) and 4 (EHV-4). A recent report by W. David Wilson, BVMS, MRCVS, MS, of the Department of Medicine and Epidemiology in the School of Veterinary Medicine at the University of California, Davis, indicates that for years the wrong approach has been taken. That approach involved vaccinating foals at a very early age to protect them against disease.
It has now been learned that vaccinating before the foal reaches at least six months of age does more harm than good, because maternal antibodies passed on to the foal when he ingested colostrum multiply in response to the vaccination antigen, according to Wilson, "to exert a profound inhibitory effect on the serologic response of foals to vaccination." Thus, the foal is not producing his own immune response, and will not have a sufficient response once maternal antibodies are gone around six months of age.
It was also found, Wilson says, that it was beneficial to include a third shot in the primary series.
Compromising the System
We come now to some of the factors that can compromise this delicately balanced, complex immune system. Earlier, Gamble was quoted as saying that in his experience, the three prime factors involved in compromising the immune system were stress, nutrition, and age.
Stress, he says, can be either mental or physical. A form of mental stress might occur at weaning time for the foal. Physical stress can range from breeding overload with a stallion to a physical injury of a pleasure horse. In stressed animals, Gamble says, there often will be increased steroid production, which tends to suppress the immune system.
If horses are malnourished, he says, this negatively impacts cell production. Even the well-fed horse, he said, can be at risk of suppression of the immune system if his diet doesn't contain the necessary micro- and macro-minerals. Micro-minerals include such elements as zinc, copper, cobalt, selenium, and manganese, while macro-minerals include calcium, phosphorus, and magnesium.
Age, Gamble says, can have an effect at both ends of the spectrum--the very young and the very old. In the very young horse, the immune system is in a developmental stage, and in the old horse, its capabilities are diminished as part of the aging process.
Science has come a long way in understanding the immune system since the days of Jenner and Pasteur, but there is still much to be learned.
PROMOTING GOOD HEALTH
Human doctors and veterinarians long have known that there are adjuncts they can use in the treatment of a patient that can help promote good health. Among these treatments are vitamins and additives used to stimulate the immune system in the expectation that the person's or animal's body will then be better able to fight off illness and disease. While there is little to no research on if or why these items improve a horse's immune system, there is also little evidence of harm if they are given within proper ranges.
A newcomer to animal medicine is something called transfer factor. Discovered in the 1940s, transfer factor describes the molecules derived from cow colostrum that transfer and establish the immune system in the newborn. Transfer factor from cows is said to improve and regulate the immune system in other species, including humans. Human medical doctors have used transfer factor in situations as simple as a cold or flu, and as complicated as cancer and AIDS.
Horse owners are advised to discuss their horses' health with their veterinarians before implementing management changes. Since transfer factor is so new to large and small animal medicine, the company that holds the patent on transfer factor has help numbers available to veterinarians and horse owners to answer questions.