Keep your horse’s protective immune system functioning at every stage of his life
Do you ever wonder how it is that you travel to clinics and events away from home and, for the most part, your horse returns in good shape, with not even a sniffle? It’s largely due to a well-functioning immune system defending him from a world teeming with microorganisms. Many factors affect your horse’s ability to mount an effective immune response, one of which is his age. Basic immune mechanisms are similar in foals and adults, but cell response, regulation, and response to pathogens and vaccines do differ in these populations. In this article we’ll examine immunity across all ages.
Priming Immune Systems for Life
A newborn foal acquires protective immunity from antibodies (proteins that target and eliminate foreign bodies called antigens) he obtains from his dam’s colostrum (first milk), through a process called passive transfer. The antibodies are ones the mare has produced in response to her environment and to immunizations received in the last month of pregnancy. The protein molecules in colostrum can pass easily through the intestinal tract lining immediately after birth. By 12 to 24 hours, however, specialized cells in the foal’s intestinal lining no longer pass these large molecules through into the bloodstream. Breeders can have their veterinarians determine the extent of foals’ protection via a blood test that measures concentrations of immunoglobulin G (IgG) antibodies in serum.
“Foals are capable of producing antibodies to foreign antigens while in the womb, starting around nine months gestation,” says David Horohov, PhD, director of the University of Kentucky’s Gluck Equine Research Center, in Lexington. “Once born, they have the capability of responding to any environmental antigen they encounter, but with two limitations. First, the ability to make specific subclasses of IgG is impeded for the first couple of months by the low expression of certain cytokines (molecules that affect and modulate the behavior of other surrounding cells, such as those necessary to mount an immune response). Second, and more importantly, the presence of maternal antibodies can interfere with a foal’s own immune system’s ability to respond.”
Adaptive immunity is the foal’s second line of defense, but it only develops later in life as maternal antibodies wane and the immature immune system begins to respond to stimulation by foreign proteins. Antibodies develop, and specialized white blood cells get summoned to areas under attack. Immune cells retain a memory that allows them to respond rapidly to future insult by the same antigen.
This process is the basis of vaccination. When foals first need to be vaccinated depends on the degree of maternal antibody interference derived from the colostrum.
“Maternal antibodies remain in the foal’s circulation until approximately six months of age,” says Elizabeth Davis, DVM, PhD, Dipl. ACVIM, professor and head of the Department of Clinical Sciences at Kansas State University’s College of Veterinary Medicine, in Manhattan.
At this point, foals need the first of their three-dose series of core vaccines (rabies, tetanus, West Nile virus, Eastern/ Western equine encephalitis). Veterinarians typically administer the first dose at 4 to 6 months of age, followed by a booster approximately one month later and a third dose two to three months after that.
“Boosters are then administered once or twice annually according to manufacturer recommendations and environmental risks,” she adds.
Foals might begin receiving immunization against viral respiratory diseases at 6 months of age, with a series of three given over four- to six-week intervals. Regardless of when these vaccines are initiated, foals should receive influenza and rhinopneumonitis boosters at 10 to 12 months of age.
Keep in mind that weaning is a stressful time that renders a foal more susceptible to infection because increased cortisol (the stress hormone) diminishes cell-mediated immunity (which does not involve antibodies but, instead, relies on other cellular responses to antigens.)
Factors Affecting Adult Horses
Owners should work with their veterinarians to construct a vaccination program that includes core and risk-based vaccines for each horse. Amanda Adams, PhD, assistant professor at the Gluck Equine Research Center, says that because horses’ vaccine responses vary greatly, it is important to follow American Association of Equine Practitioners (AAEP) guidelines for immunization (aaep.org/vaccination-guidelines), ensuring horses receive core vaccines at least annually and more often in areas with year-round exposure to endemic diseases such as West Nile virus and encephalitis. She also stresses the importance of following vaccine manufacturers’ labels for duration of protection, along with your veterinarian’s recommendations.
Some factors beyond immunization, however, can affect a horse’s level of immunity. We’ll describe three here.
Did you know that a large percentage of the equine immune system is located in the gut? “An imbalance in the gut microbiota allows overgrowth of ‘bad’ microbes,” says Adams. “This stimulates an inflammatory response that damages the intestinal lining and contributes to or causes a ‘leaky gut.’ ”
With a leaky gut, says Davis, “severe damage to the intestinal lining may limit its ability to maintain an effective barrier between intestinal contents and the bloodstream. Bacteria and/or bacterial products (endotoxin) may enter the circulation, resulting in sepsis. Such a systemic infection significantly reduces white blood cell numbers, which markedly impairs immune function.
“A vicious cycle continues because inflammatory cells within the gut wall activate resident immune cells and/or recruit more immune cells,” she adds. “Leaky gut syndrome leads to a number of problems, including malabsorption of nutrients, autoimmune diseases, and systemic inflammation, which in turn contributes to many chronic diseases.”
The immune system demands a lot of nutrients and energy to maintain homeostasis (stability) and function. “This delicate dance between gut microflora and the immune system is a relationship one wants to keep happy with appropriate nutrition and management,” says Adams.
Both she and Davis recommend practical ways to achieve this: a balanced diet, abundant roughage, minimal processed concentrate, and routine exercise.
Davis also advises avoiding antimicrobial therapy unless veterinarian-prescribed to treat a condition. “Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) can have marked detrimental effects on the gastrointestinal health of horses, including a direct toxic effect to intestinal lining (epithelial) cells,” she says. “In extreme situations, NSAIDs irritate the intestinal lining, potentially leading to protein loss and diarrhea.”
Davis says she can’t overemphasize the importance of a healthy gastrointestinal tract on a horse’s immune system. “For high-stress situations associated with competition or in combination with (the antibiotics or NSAIDs described), additional nutritional aids, like probiotics (live organisms), may be indicated,” she adds. “Horse owners should work with their veterinarians to determine which probiotic products contain appropriate ingredients that are ideal for horses.”
Adams describes one study she and colleagues performed in collaboration with Purina Mills on 40 senior horses, in which they found that a specific dose of a prebiotic (plant fiber that promotes probiotic growth) added to the horses’ diets reduced inflammation and improved immune responses to vaccination.
A competent immune system also needs certain nutrients to function well: amino acids (methionine, arginine, glutamine); trace minerals (zinc, copper, selenium); vitamins (folate, B6, B12, vitamins C, A, D, E); and polyunsaturated fatty acids.
Low- to moderate-intensity exercise benefits the immune system. High-intensity exercise or exercise for long durations (as experienced by endurance athletes), on the other hand, might put horses more at risk of developing lung infections due to short-term immunosuppression soon after exercise. Scientists believe horses might inhale normal bacterial inhabitants in the back of their throat into the lower airways during intense exercise. Because airway turbulence during high speeds might adversely affect the respiratory tract lymphocytes’ (a type of white blood cell) immune competence, bacterial infections might ensue as microorganisms proliferate. Stress-induced immunosuppression that occurs during travel, competition, and changes in routine adds to infection risks.
In recreational and competitive sport horses cortisol concentrations increase temporarily following exercise, but they do so in a beneficial way that increases neutrophil (another type of white blood cell) bactericidal activity.
Researchers have shown that conditioning is associated with health benefits for the immune system. “However, this response in aged horses differs from younger horses and remains diminished, even with conditioning,” says Adams.
In 2013 Liburt et al. demonstrated that the pituitary and adrenal glands experience declining function with age, but exercise training helps counteract these deficits by improving the hormonal (hypothalamic-pituitary-adrenal) axis function. This axis intertwines the endocrine and nervous systems and serves as a stress control center for all body functions.
In human medicine doctors have associated obesity with a “pro-inflammatory” state. Severely overweight people often have reduced responses to vaccination and increased susceptibility to infectious disease. In horses, says Adams, obesity similarly contributes to inflammation in both systemic and local tissues.
“There is clear evidence that obesity in equine metabolic syndrome (EMS)-prone horses has negative health effects besides insulin dysregulation (hyperinsulinemia, defined as excess levels of insulin in the blood due to overproduction in response to glucose, or insulin resistance, defined as a decrease in tissue sensitivity to insulin), which predisposes to laminitis,” says Davis. “Some horses may not demonstrate obvious obesity, yet may have metabolically active adipocytes (fat cells).”
Dianne McFarlane, DVM, PhD, MS, Dipl. ACVIM, professor of physiological sciences at Oklahoma State University’s Center for Veterinary Health Sciences, in Stillwater, says that, “in people, adipose depots (fat stores) directly release inflammatory mediators that add to systemic inflammation. Not all adipose tissue is equally damaging. Evidence supports that adipose deposits in horses, particularly fat stored in the neck, is most active in driving systemic inflammation.”
Adams and her group examined equine antibody production in response to vaccination and found no differences between EMS and non-EMS horses. “However,” she says, “comparable to data seen in humans, EMS horses demonstrate a lower cell-mediated response to vaccination than non-EMS horses.”
Until challenge studies are performed, in which researchers expose horses to the antigens the vaccines protect against, we don’t know if a reduced immune response to vaccination means a horse is not well-protected.
“Due to the risk of adverse effects on immunity and increased risk of contracting disease due to obesity, it is ideal to routinely examine horses’ body condition while maintaining exercise and nutritional programs that foster a healthy body condition score,” says Davis.
Declining Immune Function With Age
As horses live longer thanks to excellent management and veterinary care, we see syndromes not previously recognized in horses in their late teens or early 20s. Veterinarians consider horses over the age of 20 geriatric. These animals decline in obvious ways, including lost muscle tone, diminished body condition scores, and an overall reduced well-being.
Researchers debate whether such physical changes are the source of declining immune function or the result of it, referred to as inflamm-aging or immunosenescence.
“Inflamm-aging is the result of chronic, lifelong exposure to triggers to the immune system,” says McFarlane. “Exposure to environmental toxicants, poor diet, changes in gut bacterial flora, persistent viral infections, and chronic inflammatory diseases may tip the balance from a protective immune system to a detrimental inflammatory state.”
Adams describes the chronic inflammatory process: “Lymphocytes are part of a horse’s adaptive immune activity; these white blood cells respond to invasion by specific foreign antigens. But with age, exhausted lymphocytes or those that no longer divide (differentiate into various immune responders) are sources for production of significant amounts of inflammatory cytokines. Macrophages, another cell population responsible for inflamm-aging, are likely reacting to molecules from cellular debris that accumulates with age.” This debris stimulates inflammation, which adversely affects the immune system.
“The hallmark characteristics of immunosenescence … include reduced T cell (a lymphocyte integral to cell-mediated immunity) proliferation and function, reduced immune responses to vaccination, and the inflamm-aging process,” she continues. “All these factors contribute to age-related increased susceptibility to disease, both infectious and noninfectious.”
She believes the clinical effects of “aging” might simply be due to the immune system’s decline as a horse gets older.
In her research Adams has also identified seasonal changes in senior horses’ immune function, immune cell proliferation, and cytokine production. Inflammatory levels peak in the spring and drop in late summer into winter. However, she says, “neither season nor hormones are the cause or driving factor of inflamm-aging.” Rather, age and obesity have greater effects on increased cytokine production and the resulting inflammation.
Approximately one-third of the older horse population is affected by pituitary pars intermedia dysfunction (PPID, or equine Cushing’s disease), adding another layer of immunosuppression to normal age-related influences. Study results indicate that antibody titers (which reflect protection against disease) don’t persist as long in PPID-affected horses.
“Increased adrenocorticotropic hormone due to PPID leads to abnormal adrenal cortisol synthesis and release, which has immunosuppressive effects,” says Davis. “PPID-affected horses demonstrate a variety of clinical signs: increased sweating, increased water intake, improper shedding, and a persistently long hair coat, along with diminished immune function. They often suffer from chronic infections, such as dental disease, sinusitis, and parasitic disease.”
Based on her research, Adams reports that she and others don’t see differences between PPID and non-PPID aged horses’ adaptive immune response. Also, when comparing immune responses to vaccination, they did not notice antibody differences in how the horses responded to the influenza component of a combination vaccine. “However, there are differences in how PPID horses respond to West Nile virus and equine herpesvirus components of combination vaccines,” she says (TheHorse.com/112280).
Therefore, she says, it might be better to give senior horses single injections of each vaccine antigen rather than combining multiple antigens into one injection. Her study group is also investigating pergolide (for PPID) treatment’s effects on aged horses’ immune systems.
The Importance of Preventive Care
The key to maintaining good health and immunity in horses of all ages? An effective vaccine and deworming program, quality nutrition, conditioning, and biosecurity measures to reduce risk of exposure to infection, says Davis.
“Don’t forget about your older horses or assume they don’t need vaccination,” Adams adds. “Maintain geriatric horses, especially PPID horses, on a regular vaccination program. This is most critical for horses still in training, competition, and travel.
“Decreasing immune function with advancing age also hampers the ability of the immune system to keep parasite burdens in check,” she adds. “A study done in collaboration with parasitologist Martin Nielsen, DVM, PhD, Dipl. EVPC, of Gluck Equine Research Center, identified that old horses had significantly higher fecal egg counts (FECs, which are evidence of parasite infection) compared to young adult horses. Both groups responded well to two different classes of anthelmintic treatment, with FECs significantly reduced after deworming.”
Adams recommends following similar AAEP deworming guidelines for both adult and senior horses: Fecal egg counts once or twice a year; FEC reduction testing to assess dewormer efficacy; and deworming treatments focused on peak transmission seasons (spring and fall).
Biosecurity practices are also important for all equine populations, but the young and old are most susceptible to infectious diseases, says Davis.
“Separate new from resident horses for two to four weeks following arrival, handle new arrivals after caring for the resident population, and check daily for body temperature, changes in respiratory character, cough, nasal discharge, and fecal character or consistency,” says Davis. “Implementing herd health practices by vaccinating all horses against infectious diseases substantially diminishes the risk of disease at the individual level by maximizing herd immunity.”
You can find the AAEP’s biosecurity guidelines at https://bit.ly/2Hdal6o.
For optimal immune function in any horse, minimize stress, supply quality nutrition, provide preventive care through vaccination and deworming programs, and facilitate exercise and conditioning to maintain a healthy body condition score. Finally, limit your horse’s risk of exposure to pathogens by implementing optimal biosecurity practices.