The immune system and mastitis

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Poor cow health and high somatic cell counts (SCCs) often go hand in hand, and the result is often mastitis. This is most likely related to stress on the immune system which impairs its functionality, says Patrick Gorden, DVM, Dipl. ABVP-Dairy, Iowa State University. Additionally, antibacterial agents alone cannot control an intramammary infection (IMM) infection without the assistance of a functional immune system. Depending on the stage of lactation and presence of IMM infections, the immune system has varying levels of functionality.

The cow’s first line of defense against the introduction of mastitis-causing pathogens is the skin and muscular teat sphincter. The streak canal is lined with keratin that traps bacteria and then is removed with milking. Keratin is a waxy material that is derived from stratified squamous epithelium. Keratin’s structure enables trapping of invading bacteria, thus hindering their migration into the gland cistern. Within the keratin lining are natural antimicrobial agents which are bacteriostatic. Teat injuries, teat surgery and infusions all remove the protective keratin and increase the risk of mastitis. “An additional physical barrier is provided by the process of milking, which serves a protective function in that it flushes the contents out of the mammary gland on a regular basis,” Gorden says.

The most important defense system, however, is the innate immune system. “The innate system serves a role to detect and kill an array of pathogens,” Gorden notes. “A decrease in the function of even one component of the innate immune system can have detrimental effects on the cow’s immune response.”

Gorden explains that polymorphonuclear cells (PMN) including neutrophils, basophils, and eosinophils, play a key role in the innate immune system by detecting and containing infectious agents. While basophils and eosinophils have important functions, the neutrophil becomes the most important PMN for the mammary gland in dealing with IMM bac-terial infections.

Derailing the immune system

The lactating cow’s immune system is already somewhat derailed due to normal immune suppression associated with calving and lactogenesis. “Calving and lactogenesis seem to have independent effects on immune suppression,” Gorden says. “Negative energy balance during the pre- and post-partum period have a suppressing effect but negative energy balance during mid-lactation has been shown to only have a minimal effect. This suggests that there are factors associated with calving and lactogenesis that are associated here also.” Gorden adds that the development of ketosis has been shown to cause severe mastitis infection as compared to negative energy balance alone.

Gorden notes that researchers at the USDA’s National Animal Disease Center in Ames, Iowa did a study several years ago in which they mastectomized cows and compared the immune function of the mastectomized cows vs. intact cows. In both groups, there was an immune suppression associated with calving and in that trial there was a sudden increase in cortisol the day before calving in both groups. “There is substantial immunosuppression associated with calving and it is probably presumptive to think that cortisol may be the only element causing this immunosuppression,” Gorden explains.

A 2003 Bovine Veterinarian article described research done by Mark Kehrli, DVM, PhD at the National Animal Disease Center-USDA-ARS that showed that cows with severe metritis or retained placentas mobilized virtually all of their circulating immune cells (e.g., neutrophils) to fight uterine infections. This mobilization left very few neutrophils in the blood stream to fight an infection that might start elsewhere in the body, such as the mammary gland. Kehrli said these cows might develop an infection in the mammary gland that goes unchecked for a few hours until the circulating blood neutrophil numbers are restored from the bone marrow. By that time, it is too late for the cow and the infection in the udder may have grown so much that the disease now overwhelms her with a severe peracute case of mastitis.

Calcium is also involved with immune suppression. There are factors associated with intracellular signaling of mononuclear cells that occur two to three weeks prior to calving. “This has a negative impact on immune function by causing slower movement of these cells into infected areas in addition to the effects of calcium in the periparturient period,” Gorden explains. Research has shown that intracellular calcium plays a vital role in peripheral blood mononuclear cell (PBMC) activation. Calcium deficiency will result in less complete closure of the teat sphincter and will result in increased lying time, thus exposing the cow to more pathogens and result in increased mastitis.

Gorden adds that as cows age, there appears to be a decrease in immune function as evidenced by older animals being more severely affected by infectious agents. This reduced function is related to impaired function of neutrophils along with a reduced production of reactive oxygen species in older animals.

Other factors such as poor nutrition, inadequate vaccination, parasite load, poor environment/high pathogen load, high production, stress and others contribute to immune suppression. “Mastitis, like other diseases, is multi-factorial, so often there is more than one negative factor occurring,” Gorden says. “Immune suppression is more severe with other problems such as retained placenta, twinning, lameness and dystocia.”

High milk production does not have a genetically related negative impact on immune function; however, high-producing cows tend to have more mastitis than lower-producing cows. This most likely can be explained by being more prone to negative energy and protein balance and the fact that higher-producing cows also have wider streak canals which makes them more prone to infections.

“Protein metabolism is equally important in the development of immune suppression around parturition,” Gorden states. “Cows are in negative energy balance for 45 to 75 days postpartum. They are also in negative protein balance for a similar period of time. The development of an immune response against an infection is not without expense to energy and protein metabolism.”

Chronic mastitis in the late dry period has been shown to decrease the volume of colostrum and the total IgG level compared to uninfected cows, but not the concentration of IgG/ml,
Gorden says.

Help her regain balance

Prior to and after parturition maximizing dry matter intake by providing sufficient amounts of properly balanced feed can help the cow maintain proper energy balance. Gorden recommends providing the cow with adequate resting space and adequate bunk space (at least 30-in./cow) prior to calving, which is also important in the post-partum period. “In addition, minimizing pen changes prior to calving will promote better dry matter intake and lower incidence of metabolic problems,” he says. “It is extremely important to monitor dry matter intake to make sure the cows are actually eating what they are supposed to be. Measures to prevent hypocalcemia (subclinical and clinical) must be incorporated into transition cow program.”

Adequate levels of vitamins A and E as well as selenium are also needed to insure that the mammary gland immune system functions at its maximum capacity. The University of Pennsylvania New Bolton Center recommends that during lactation cows should receive 400–600 IU vitamin E and .3 ppm of selenium per day. During the dry period, cows should get 1000 IU vitamin E and .3 ppm selenium per day.

Gorden suggests that the most practical approaches for today’s dairyman include a combination of improving and maintaining cow hygiene, managing diets around the periparturient period to minimize dry matter intake and hypocalcemia, and implementing procedures to minimize cow stress. “It is inevitable that there will be a certain amount of immune suppression even in the best conditions,” he says. “However, implementing good management practices should help minimize this.” 


Trace minerals and immunity

Several trace minerals and vitamins influence the immune system which can have an effect on its defenses against mastitis pathogens.

SELENIUM
Function:
Improves bactericidal capabilities of neutrophils. Decreases severity and duration of mastitis. Enhances neutrophil killing of Staphylococcus aureus, Candida albicans andE. coli.

Deficiency: Decreased efficiency in neutrophil function


VITAMIN E

Function:
Increased neutrophil bactericidal activity.

Deficiency: Decreased incidence of clinical mastitis. In combination with Se, decreased prevalence of IMI at calving.


VITAMIN A

Function:
Decreased somatic cell count. Moderated glucocorticoid levels. Stimulates immune cell populations.

Deficiency: Increased severity of mastitis.


BETA-CAROTENE

Function:
Increased bactericidal function of phagocytes. Increased mitogen-induced proliferation of lymphocytes. Stimulates immune cell populations.

Deficiency: Increased severity of mastitis.


COPPER

Deficiency:
Decreased neutrophil killing capability. Increased susceptibility to bactericidal infection.


ZINC

Function:
Linked to proper immune function. Essential for integrity of skin, physiologic barriers.

Deficiency: Decreased leukocyte function. Increased susceptibility to bacterial infection. High calcium diets can exacerbate zinc deficiency problems.


Source: Lorraine Sordillo, PhD, The Pennsylvania State University, “Mastitis and Immunology,”
Bovine Veterinarian, July–August 1998.


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