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Optimize Your First 100 Days in Milk

Optimize Your First 100 Days in Milk

with OmniGen-AF®

Every day, your cows face stressors that can lead to certain health challenges and, ultimately, challenges to production. These could include reduced milk yields and higher unit costs, as well as additional labor and treatment costs. Fortunately, you have nutritional support that can help optimize production.

Click on the image at right to look at some important results from research trials about cows fed OmniGen-AF.

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Help Your Cows Handle the Heat with OmniGen-AF® Nutritional Specialty Product.

Help Your Cows Handle the Heat

with OmniGen-AF® Nutritional Specialty Product.

Heat is one of many stressors that can affect your herd’s health and productivity.

Fortunately, research has shown that cows fed with OmniGen-AF nutritional specialty product maintained healthy immune function and overall productivity better than cows who weren’t, during and after heat stress conditions. Click on the image at right to look at some important results from university and research trials.

Click on image to read more.

Click here to learn more.
Click here to learn more.

Heat Stress Management with OmniGen Nutritional Specialty Product

Heat Stress Management with OmniGenTM Nutritional Specialty Product

Cattle are susceptible to a wide range of stressors on the farm, heat being one of the most common. Being proactive is the best approach to help manage the short- and long-term consequences of heat stress. OmniGen nutritional specialty product from Phibro Animal Health can help protect your herd from the negative impacts of stress caused by typical heat stress conditions. Click on this video to learn more.

Nutritional and Management Considerations Before, During & After Heat Stress

Keep Cool

Dairy Cow Immunity Impacts Reproductive Performance – Advisory


A. Rowson, DVM and D. Kirk, Ph.D., PAS
Phibro Animal Health Corporation, Quincy, IL

Impaired reproductive performance of dairy cows can have significant impact on the profitability of dairy operations.  The immune system has been shown to play a role in dairy cow reproduction, both indirectly, through the effects of mastitis, metritis, retained placenta, and metabolic diseases; and directly, through actions of immune cells upon the ovary.  A properly-functioning immune system may help improve reproductive performance of dairy cattle by reducing occurrence of diseases affecting fertility, and improving immune cell activity.


The cow’s estrous cycle is approximately 21 days long.  It is divided into two phases which are characterized by changes on the ovary.  The follicular phase makes up 20% of the cycle.  During this phase the pre-ovulatory follicle on the ovary, which contains the oocyte (or egg), produces estrogen.  When estrogen concentrations are high enough, a surge of luteinizing hormone (LH) is released, initiating ovulation. The luteal phase begins after ovulation, when the follicle transforms into a corpus luteum (CL) which produces progesterone to maintain pregnancy.  This phase makes up the remaining 80% of the estrous cycle.


Reproductive performance is monitored using several metrics:
Calving Interval   Period between calvings
Days Open   Period between calving and confirmed conception
Services Per Conception   Total services per total number of pregnant cows
Heat Detection Rate   Percent of eligible cows that are bred
Conception Rate   Percent of cows bred that are pregnant
Pregnancy Rate   Percent of cows eligible to become pregnant that are confirmed pregnant during a given period (usually 21 days)


Reproductive performance is affected by both breeding success and pregnancy loss. Typically, gestation lasts 280 days. Up to 40% of pregnancies are lost in first 17 days of gestation. Early embryonic loss occurs from 0 to 15 days of gestation, and is usually not detected since pregnancy loss at this stage does not delay estrus. Late embryonic loss occurs at 16 to 41 days of gestation, and will delay ovulation and thus extend the estrous cycle. Embryonic losses usually occur before pregnancy is confirmed. Abortion occurs between 42 to 260 days of gestation, and stillbirths occur from 260 days of gestation through birth. “Normal” abortion rates are 3% to 5% per year.


Mastitis is associated with: increased Days Open1,2; greater Services/Conception2; reduced Conception Rate3,1; reduced Pregnancy Rate4,1; higher incidence of Early Embryonic Death5,6; and greater risk of abortion7,1. Infection of the udder affects the structure and function of the ovaries8 and has also been associated with altered patterns of reproductive hormone secretion4. These effects may be linked to a systemic response by cytokines9 (molecules released by cells that affect actions of other cells, particularly immune cells) which may also lead to pregnancy loss10.

Retained placenta can also have indirect effects upon fertility, including: reduced Conception Rate3; lower Pregnancy Rate11; more Services per Conception12; and increased Days Open13. Retained placenta is associated with reduced neutrophil function and lower blood concentrations of interleukin-814 (IL-8, a cytokine that attracts immune cells to sites of infection), and may alter activities of the CL15.

Uterine disease, which includes metritis (inflammation of the entire uterus) and endometritis (inflammation of the uterine lining), is associated with: lower Conception Rate16; reduced Pregnancy Rate11; and increased Days Open17. Uterine disease appears to have the greatest impact on fertility by reducing ovulation rate18 and CL size19 during the first post-partum estrous cycle. Cows with uterine disease also have smaller follicles and lower blood estrogen concentrations20. Cows that develop uterine disease experience reduced neutrophil function around the time of calving21,22.

Metabolic diseases are also associated with impaired reproductive performance.

  • Milk fever increases Days to 1st Service11
  • Subclinical hypocalcemia reduces 1st Service Conception Rate23
  • Ketosis increases Days to 1st Service & decreases 1st Service Conception Rate11
  • Mastitis combined with other diseases has greater negative impact on reproduction than any one disease alone24

Immune cells, primarily neutrophils, macrophages, and T-lymphocytes, are required by the ovary for normal ovulation and CL function25. Activities of these immune cells are regulated by the luteal environment, and result in both CL development and regression26. Neutrophils migrate into the early CL (day 1 to 4 of the estrous cycle), in response to IL-8 produced by the CL. Neutrophil numbers and IL-8 concentrations are low at the mid- and late-luteal phase but IL-8 is high at luteal regression. Interestingly, cortisol (a potent, immunosuppressive hormone released in response to stress) acts to block the release and peak of LH from the pituitary gland, which can prevent ovulation.

The immune system has both direct and indirect effects upon reproduction in dairy cows. Reproductive performance may be improved with a properly-functioning immune system.

1Santos, J. E. P., R. L. A. Cerri, M. A. Ballou, G. E. Higginbotham, J. H. Kirk. 2004. Effect of timing of first clinical mastitis occurrence on lactational and reproductive performance of Holstein dairy cows. Animal Reproduction Science 80:31–45.

2Schrick, F. N., M. E. Hockett, A. M. Saxton, M. J. Lewis, H. H. Dowlen, and S. P. Oliver. 2001. Influence of subclinical mastitis during early lactation on reproductive parameters. J. Dairy Sci. 84:1407–1412.

3Hertl, J. A., Y. T. Gröhn, J. D. G. Leach, D. Bar, G. J. Bennett, R. N. González, B. J. Rauch,
F. L. Welcome, L. W. Tauer, and Y. H. Schukken. 2010. Effects of clinical mastitis caused by gram-positive and gram-negative bacteria and other organisms on the probability of conception in New York State Holstein dairy cows. J. Dairy Sci. 93:1551–1560.

4Hockett, M. E., R. A. Almeida, N. R. Rohrbach, S. P. Oliver, H. H. Dowlen, and F. N. Schrick. 2005. Effects of Induced Clinical Mastitis During Preovulation on Endocrine and Follicular Function. J. Dairy Sci. 88:2422–2431.

5Chebel, R. C., J. E. P. Santos, J. P. Reynolds, R. L. A. Cerri, S. O. Juchem, and M. Overton. 2004. Factors affecting con- ception rate after artificial insemination and pregnancy loss in lactating dairy cows. Anim. Reprod. Sci. 84:239.

6Moore, D. A., M. W. Overton, R. C. Chebel, M. L. Truscott, and R. H. BonDurant. 2005. Evaluation of factors that affect embryonic loss in dairy cattle. J. Am. Vet. Med. Assoc. 226:1112.

7Risco, C. A., G. A. Donovan, and J. Hernandez. 1999. Clinical mastitis associated with abortion in dairy cows. J Dairy Sci. 82:1684–1689.

8Rahman, M. M., M. Mazzilli, G. Pennarossa, T. A. L. Brevini, A. Zecconi, and F. Gandolfi. 2012. Chronic mastitis is associated with altered ovarian follicle development in dairy cattle. J. Dairy Sci. 95:1885–1893.

9Chebel, R. C. 2007. Mastitis effects on reproduction. NMC Regional Meeting Proc. (2007):43–55.

10Soto, P., R.P. Natzke, and P.J. Hansen. 2003. Identification of possible mediators of embryonic mortality cause by mastitis: actions of lipopolysaccharide, prostaglandin F2α, and the nitric oxide generator, sodium
nitroprusside dihydrate, on oocyte maturation and embryonic development in cattle. Am. J. Reprod. Immunol. 50:263.

11Fourichon, C., H Seegers, and X. Malher. 2000. Effect of disease on reproduction in the dairy cow: a meta-analysis. Theriogenology 53:1729–1759.

12Joosten, I., J. Stelwagen, A. A. Dijkhuizen. 1988. Economic and reproductive consequences of retained placenta in dairy cattle. Veterinary Record 123, 53–57.

13Yeon-Kyung, H and K. Ill-Hwa. 2005. Risk factors for retained placenta and the effect of retained placenta on the occurrence of postpartum diseases and subsequent reproductive performance in dairy cows. J. Vet. Sci. 6(1), 53–59.

14Kimura, K., J. P. Goff, M. E. Kehrli, Jr. and T. A. Reinhardt. 2002. Decreased Neutrophil Function as a Cause of Retained Placenta in Dairy Cattle. J. Dairy Sci. 85:544–550.

15Holt, L. C., W. D. Whittier, F. C. Gwazdaukas, and W. E. Vinson. 1989. Early Postpartum Reproductive Profiles in Holstein Cows with Retained Placenta and Uterine Discharges. J. Dairy Sci. 72:533–539.

16Dubuc, J., T. F. Duffield, K. E. Leslie, J. S. Walton, and S. J. LeBlanc. 2011. Effects of postpartum uterine diseases on milk production and culling in dairy cows. J. Dairy Sci. 94:1339–1346.

17Giuliodori, M. J., R. P. Magnasco, D. Becu-Villalobos, I. M. Lacau-Mengido, C. A. Risco, and R. L. de la Sota. 2013. Metritis in dairy cows: Risk factors and reproductive performance. J. Dairy Sci. 96:3621–3631.

18Herath, S., H. Dobson, C. E. Bryant, and I. M. Sheldon. 2006. Use of the cow as a large animal model of uterine infection and immunity. Journal of Reproductive Immunology 69 (2006) 13–22.

19Strüve, K., K. Herzog, F. Magata, M. Piechotta, K. Shirasuna, A. Miyamoto and H. Bollwein. 2013. The effect of metritis on luteal function in dairy cows. BMC Veterinary Research 9:244–252.

20Sheldon, I. M., E. J. Williams, A. N. A. Miller, D. M. Nash, S. Herath. 2008. Uterine diseases in cattle after parturition. The Veterinary Journal 176:115–121.

21Cai, T. Q., P. G. Weston, L. A. Lund, B. Brodie, D. J. McKenna, and W. C. Wagner. 1994. Association between neutrophil functions and periparturient disorders in cows. Am. J. Vet. Res. 55:934–943.

22Hammon, D. S., I. M. Evjen, T. R. Dhiman, J. P. Goff, and J. L. Walters. 2006. Neutrophil function and energy status in Holstein cows with uterine health disorders. Vet. Immunol. Immunopath. 113:21–29.

23Chapinal, N., M. E. Carson, S. J. LeBlanc, K. E. Leslie, S. Godden, M. Capel, J. E. P. Santos, M. W. Overton, and T. F. Duffield. 2012. The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance. J. Dairy Sci. 95:1301–1309.

24Ahmadzadeh, A., M. A. McGuire, J. C. Dalton. 2010. Interaction between Clinical Mastitis, Other Diseases and Reproductive Performance in Dairy Cows. WCDS Advances in Dairy Technology Volume 22:83–95.

25Walusimbi, S. S., and J. L. Pate. 2013. Physiology and Endocrinology Symposium: Role of immune cells in the corpus luteum. J. Animal Sci., 91:1650-1659.

26Jiemtaweeboon, S., K. Shirasuna, A. Nitta, A. Kobayashi, H. J. Schuberth, T. Shimizu and A. Miyamoto. 2011. Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow. Reproductive Biology and Endocrinology 9:79–88.


OG010215 © 2015 Phibro Animal Health Corporation.

Beat the heat this summer

Beat the heat this summer

It has long been known that heat stress adversely affects production and reproduction in dairy cows worldwide. In the United States alone, Normand St-Pierre and co-workers at The Ohio State University have estimated that annual economic losses to heat stress in the dairy industry exceed $900 million per year.

A 2002 report estimated that 48 percent of dairy cows, or 4.2 million, in the United States are subjected to thermal or heat stress on an annual basis, negatively affecting milk yield, reproduction and health. Heat stress is unique in that it not only raises net energy requirements for maintenance but simultaneously reduces intake, which exacerbates the milk yield decline attributed to it.

However, not all of the reduction in milk yield during heat stress is associated with reduced feed intake. Research by Baumgard and Rhoads at the University of Arizona demonstrated that more than half of the milk loss in heat-stressed dairy cows is unrelated to a reduction in dry matter intake. Furthermore, the dairy cow shifts its metabolic fuel consumption during heat stress, burning more glucose and fewer nonesterified fatty acids.

The cow’s “lack of ability” to utilize body fat as a fuel during heat stress seems to be a metabolic adaptation to, in essence, preserve itself. Considerable work remains to further define the most effective nutritional strategies to minimize the impacts of heat stress on production in lactating dairy cows and to fully understand the metabolic alterations that occur in heat-stressed dairy cows.

Help them lose heat

Basic strategies to reduce the impact of heat stress include altering the environment around the cow by reducing heat gain (providing shade) and elevating heat loss (fans, soakers and evaporative cooling). In addition, producers and their advisers employ a number of nutritional strategies to maximize energy intake during periods of thermal stress. These include altering feeding times to allow more feed intake at night when it is cooler, increasing the energy density of the ration to reduce gut fill, providing high-quality forages and using total mixed rations to reduce feed sorting by cattle.

In addition to production losses, disease incidence and the immune system are compromised in heatstressed cows. This is associated with the release and elevation of cortisol common at the initial exposure to heat. Dry matter intake is compromised, and the cow’s mechanisms to digest and utilize nutrients are altered. As the cow’s system works to get rid of heat, it shunts nutrients to its extremities to aid in heat dissipation.

In reducing the cow’s heat load, nutrients are “freed up” to be utilized for more productive tasks, such as milk production, reproduction and immune function. Utilizing strategies to help cows deal with heat dissipation physically, with well-defined management protocols and, metabolically, with proven nutrition programs, alleviates the severity of heat stress and supports a faster recovery of the immune system. With this reduction in heat stress that the cow perceives, cortisol levels will begin to return to normal. This may result in improved health and productivity after periods of heat stress.

As dairy producers make plans to prepare for heat stress season, it’s important to double check the operation of and clean all fans, and test and service sprinklers, soakers or evaporative cooling systems. Work with your nutritionists to plan for necessary ration changes. When considering new or novel nutritional strategies to support normal health and immune status during heat stress, ask for a review of supporting research before making a final decision.


J.P. Jarrett

R.J. Collier

Stress & Health (Part 1 of 2)

Relationship Between Stress and Health in Cattle

Part 1

Jeffery A. Carroll, PhD and Nicole C. Burdick Sanchez, PhD
Livestock Issues Research Unit, USDA-ARS


Today, the scientific community and producers alike acknowledge the fact that “stress” can potentially have detrimental effects on animal productivity, and overall health and well-being (Carroll and Forsberg, 2007).
Even though the debate among animal scientists concerning the definition and quantification of “stress” is ongoing, an increased understanding and appreciation with regard to the effects of
“stress” on livestock production now exists both within the scientific community and with livestock producers.
While the physiological consequences of “stress” on the body have been of scientific interest for many years, scientists have yet to fully elucidate the complex interactions among stress hormones and the immune system. However, there is substantial literature available documenting the detrimental effects of prolonged stress on the immune system and overall health of livestock (Moberg, 1987; Dobson et al., 2001; Shi et al., 2003).

So What is “Stress”?

Stress, as it relates to bodily functions, has been defined as the sum of all biologic reactions to physical, emotional, or mental stimuli that disturb an individual’s homeostasis. Therefore, a stressor can be defined as any internal or external stimuli or threat that disrupts homeostasis of the body, and elicits a coordinated physiological response in an attempt to reestablish

Maintaining a state of homeostasis requires proper functioning of all physiological processes including the stress and immune systems which are influenced by numerous factors including
environmental conditions, pathogen exposure, genetic makeup, animal temperament, and nutrient availability.

Research related to “stress” in domestic animals continues to evolve and expand, with emergent multidisciplinary efforts leading to a greater understanding of homeostatic regulation. Not only has the definition of “stress” been refined and updated based upon continued scientific discoveries, but the perception of “stress” in domestic animals has evolved as well.

Stress, as we now know, includes indices such as environmental stress, nutritional stress, social stress, and even prenatal stress. Animal stress is now identified as a unique event that elicits a
specific behavioral, physiological, neuroendocrine, endocrine, and/or immune response that may be as unique as the stressful event itself.

There has been an increased effort to elucidate the interactions between stress responsiveness and immunological parameters in cattle that may be either predisposed to or resistant to the
detrimental effects of stress due to genetic programming and/or prior experiences.

Interestingly, there are cattle that demonstrate differential stress and immunological responses due to previous exposure to various managerial, environmental, nutritional, or pathogenic stressors or due to varying temperaments within a genetically similar group of animals (Carroll and Forsberg, 2007; Burdick et al., 2011; Burdick et al., 2012).

Cortisol and Animal Health

Often considered the second line of defense is the suppression of the primary immune defense by cortisol.

Suppression of the inflammatory and immune systems by cortisol prevents excessive and chronic stimulation of these systems which could prove deadly to the animal. Specifically, cortisol suppresses the release of various cytokines produced by cells of the immune system which can cause systemic disease.

Chronic exposure to high concentrations of cortisol can cause severe physiological and psychological problems such as excessive protein catabolism, hyperglycemia, immunosuppression, and depression.

In domestic livestock, excessive concentrations of cortisol have been linked to reduced rates of reproduction, suboptimal growth, suppressed milk production, and suppression of immune function that could increase susceptibility to disease (Lay et al., 1992; Buckham Sporer et al., 2008).

Depending upon the production system, cattle may be exposed to numerous stressors for varying durations that can significantly inhibit both health and productivity.

As researchers have continued to explore the complex interactions between stress and production parameters such as growth, reproduction, and health, multidisciplinary efforts have emerged that have led to a greater understanding of homeostatic regulation. Based upon these efforts, our knowledge has extended beyond the “all or none” biological activity strictly associated with the “fight or flight” response.

For instance, researchers have demonstrated that the combined immunological effects of cortisol and catecholamines result in a wellorchestrated biological event designed to prevent over-stimulation of innate immunity and the production of proinflammatory cytokines while simultaneously priming the humoral immune response in an effort to provide adequate immunological protection.


The detrimental effects caused by stressors encountered by livestock during routine handling can pose economic problems for the livestock industry due to increased costs ultimately borne by both the producer and the consumer.

Increased secretion of stress-related hormones in response to handling during management procedures may be harmful, as these hormones may inhibit physiological systems such as immunity.

Therefore, an understanding of the interaction between the stress and immune systems, and their subsequent impact on growth, is necessary in order to reduce negative impacts on growth and productivity in livestock.


Buckham Sporer, K.R., P.S.D. Weber, J.L. Burton, B. Early, and M.A. Crowe. 2008. Transportation of young beef bulls alters circulating physiological parameters that may be effective biomarkers of stress. J. Anim. Sci. 86:1325-1334.

Burdick, N.C., R.D. Randel, J.A. Carroll, and T.H. Welsh, Jr. 2011. Interactions between temperament, stress, and immune function in cattle. Int. J. Zool. 1-9.

Burdick, N.C., R. Chaffin, J.A. Carroll, C.C. Chase, Jr., S.W. Coleman, and D.E. Spiers. 2012. Influence of heat stress on the immune response of Angus and Romosinuano heifers to an LPS challenge. J. Anim. Sci. 90(E-Suppl.2):22 (Abstract # 67).

Carroll, J.A., and N.E. Forsberg. 2007. Influence of stress and nutrition on cattle immunity. Vet. Clin. North Am. Food. Anim. Pract. 23:105-149.

Dobson, H., J.E. Tebble, R.F. Smith, W.R. Ward. 2001. Is stress really all that important? Theriogenology. 55:65-73.

Lay Jr., D.C., T.H. Friend, R.D. Randel, C.L. Bowers, K.K. Grissom, and O.C. Jenkins. 1992. Behavioral and physiological effects of freeze or hot-iron branding on crossbred cattle. J. Anim. Sci. 70:330-336.

Moberg, G.P. 1987. A model for assessing the impact of behavioral stress on domestic animals. J. Anim. Sci. 65:1228-1235.

Shi, Y., S. Devadas, K.M. Greeneltch, D. Yin, R.A. Mufson, and J. Zhou. 2003. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology. Brain, Behav. Immun. 17, S18-S26.


Figure 1: When an animal perceives either an internal or external threat, neurotransmitters are released in the brain that cause the release of corticotrophin-releasing hormone (CRH) and vasopressin (VP) that stimulate the release of adrenocorticotrophin (ACTH). ACTH in turn stimulates the release of cortisol, epinephrine (Epi) and norepinephrine (NE), each of which affect various target tissues in the body including the immune system (Carroll, J.A. and N.C. Burdick. 2011. Relationships between Stress and Health in Cattle. Phibro Animal Health Corporation. Advisory Bulletin, June 2011).

Stress & Health (Part 2 of 2)

Relationship Between Stress and Health in Cattle

Part 2

Jeffery A. Carroll, PhD and Nicole C. Burdick Sanchez, PhD
Livestock Issues Research Unit, USDA-ARS


Numerous physiological and psychological conditions significantly influence the health and subsequent growth of livestock.

In domestic livestock, increased stress hormones in response to managerial stressors have been linked to reduced rates of reproduction, suboptimal growth, suppressed milk production, and
suppression of immune function that could increase susceptibility to disease (Lay et al., 1992; Buckham Sporer et al., 2008).

Through an understanding of the interactions between the stress system and immune function, animal management practices can be modified to reduce negative impacts on growth and productivity in livestock.

The Immune System

To aid in understanding the relationship between “stress” and animal health, it’s important to understand that the immune system is not a single entity, but rather a complex, integrated system regulated by a multitude of specialized cells and chemical messengers.

In general, however, the immune system can be separated into three broad components; natural immunity, innate immunity, and acquired immunity, all of which must be fully developed and functioning properly to provide adequate immunological protection.

Natural and innate immunity are typically grouped together under the category of innate immunity. Therefore, when discussing innate immunity, it is typically assumed that one is including natural immunity as well.

Innate immunity is considered to be the first line of defense against pathogens; whether bacterial, viral, protozoal or fungal. It includes physical barriers such as the skin, mucosal secretions, tears, urine, and stomach acid, as well as complement and antigen-nonspecific cellular components and is designed to elicit an immediate or acute response (0-to-4 hour) following exposure to an antigenic agent.

Until recently, the innate immune system was thought to represent the antigen-nonspecific aspect of the immune system. However, recent evidence suggests that the innate response may be specific to the pathogenic agent encountered.

While it is often assumed that this aspect of the immune system becomes a constant entity once developed by the animal, this is certainly not the case. The innate immune system, while always
present to some degree, can be modulated in either a beneficial or detrimental manner by a number of factors including wounds, dehydration, nutritional status, genetics, stress, and various peptide hormones (Figure 1).

Stress and the Immune System

As the scope of scientific exploration has expanded beyond traditionally defined pathways of neuroendocrinology, endocrinology, and immunology, multidisciplinary efforts emerged leading to the identification of cross-communication pathways among the stress and immune systems, and to a better understanding of homeostatic regulation within the animal.

No longer is stress considered strictly immuno-suppressive. Indeed, stress may elicit “bi-directional” effects on immune function such that acute stress may be immuno-enhancing, while chronic stress may be immuno-suppressive.

Today, our knowledge base has expanded, and a greater appreciation and understanding has emerged regarding the plethora of immune system activities that are influenced by cortisol such as stimulation of immune system chemical messengers, and stimulation of immune
cell growth and function (Figure 2).

In addition to these stimulatory actions, long-term exposure to cortisol is known to inhibit aspects of immune function. Ultimately, within the animal, the immune system response to
stress is dependent upon the type of stress encountered (i.e., acute versus chronic).

In some instances of acute stress, such as that resulting from bites, punctures, scrapes or other challenges to the integrity of the body, stress hormones are associated with priming the immune system in a manner to prepare for potentially invading pathogens and subsequent infection.

However, when an animal experiences prolonged or “chronic” stress, the effect of stress hormones on the immune system shifts from a preparatory event to a series of suppressive events; first at the cellular level and then eventually across the entire immune system spectrum.

While the discussion pertaining to the influences of stress on the immune system have been primarily focused on the actions of cortisol, one cannot discount the involvement of the catecholamines, epinephrine and norepinephrine, as modulators of the immune system.

An increase in circulating concentrations of catecholamines following a stressful event has been previously reported to modulate immune cell activities such as proliferation, cytokine and antibody production, cytolytic activity, and cell migration.

Continued research efforts into these complex interactions may allow the implementation of alternative management practices, improved selection programs, and/or implementation of various nutritional strategies to prevent or overcome significant production losses and animal health care costs for livestock producers.


Buckham Sporer, K.R., P.S.D. Weber, J.L. Burton, B. Early, and M.A. Crowe. 2008. Transportation of young beef bulls alters circulating physiological parameters that may be effective biomarkers of stress. J. Anim. Sci. 86:1325-1334.

Burdick, N.C., B.C. Bernhard, J.A. Carroll, R.J. Rathmann, and B.J. Johnson. 2012. Enhancement of the acute phase response to a lipopolysaccharide (LPS) challenge in steers supplemented with chromium. Innate Immunity. 18(4):592-601.

Bernhard, B.C., N.C. Burdick, W. Rounds, R.J. Rathmann, J.A. Carroll, D.N. Finck, M.A. Jennings, T.R. Young, and B.J. Johnson. 2012.

Chromium supplementation alters the performance and health of feedlot cattle during the receiving period and enhances their metabolic response to a lipopolysaccharide (LPS) challenge. J. Anim. Sci. doi:10.2527/jas.2011-4981).

Carroll, J.A., and N.E. Forsberg. 2007. Influence of stress and nutrition on cattle immunity. Vet. Clin. North Am. Food. Anim. Pract. 23:105-149.

Lay Jr., D.C., T.H. Friend, R.D. Randel, C.L. Bowers, K.K. Grissom, and O.C. Jenkins. 1992. Behavioral and physiological effects of freeze or hot-iron branding on crossbred cattle. J. Anim. Sci. 70:330-336.


Figure 1: Factors that can have a significant influence on the function of the innate immune system of cattle. Naturally occurring deviations in the innate immune system, as well as the influence of various management practices on the immune system, are often overlooked in production systems (Carroll, J.A. and N.C. Burdick. 2011. Relationships between Stress and Health in Cattle. Phibro Animal Health Corporation Advisory Bulletin, June 2011).


Figure 2. The body’s response to an antigen includes increases in stress hormones and body temperature. Cortisol and catecholamines, as well as cytokines released from immune cells, stimulate an increase in body temperature in an effort to kill invading pathogens. The above figure depicts increases in rectal temperature and serum cortisol in cattle following exposure to lipopolysaccharide (LPS). (Burdick et al., 2011.)

Steer Body Green

Figure 3. In response to an immune challenge, body resources are redirected away from growth towards the immune system, resulting in a decrease in body weight. When challenged with lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria (e.g., Escherichia coli), steers exhibited a 4.2% decrease in body weight within 24 hours (1 D Post). (Bernhard et al., 2012)

The Immune System of Ruminants

The Immune System of Ruminants

James D. Chapman, Ph.D. and Deb L. O’Connor, M.S., Dairy Technology Managers, Phibro Animal Health Corporation

Stress and Immunity in Dairy Cows

Immunity is defined by Dorland’s Illustrated Medical Dictionary, as security against a particular disease or nonsusceptiblilty to the invasive or pathogenic effects of foreign microorganisms or the toxic effect of antigenic substances. The immune system in the cow consists of two distinct but interactive systems; the innate and the adaptive or antibody mediated. Each of these has specific functions and response times but work in concert to protect the cow from infectious pathogens.

The innate system is composed of natural barriers (skin, stomach acids, enzymes, etc.) and white blood cells (neutrophils, macrophages) which continually monitor for sites of infection and pathogens and are the “first responders”. The adaptive or antibody system consists of other types of white blood cells whose function is to provide “long-term” protection against disease through the production of pathogen specific antibodies.

Stress has been defined as the sum of the biological reactions to any adverse stimulus; physical, mental, or emotional, internal or external, that tend to disturb or disrupt homeostatis, and should these compensating reactions be inadequate or inappropriate, they may lead to disorders or disease (Dorland’s Illustrated Medical Dictionary). Dairy cows can experience stress in a variety of ways, during dry off and calving, in extreme heat or cold conditions, sudden feed changes, etc. and the results of these ‘stressors’ may present itself as a case of mastitis, a retained placenta, an abrupt decline in milk production or an elevated somatic cell count.

Immune status or immune ‘health’ has been assessed using several immunological methods. One method is to assess total production of immunoglobulins (IgM and IgG’s). These are non-specific indicators of the combined titre against all antigens to which a cow is exposed. Another common measure is titre, which assesses T- and B-cell proliferation

and is an index of the adaptive immune systems ability to ‘ramp up’ to a specific chemical or mitogen challenge. More recently, scientists are using several more highly specific methods to assess immune system activity or ‘health’. These have focused on assays and procedures designed to assess the ability of certain white blood cells to kill pathogens via phagocytosis and the production of reactive oxygen species, or communicate with other immune cells through cytokine production, or maintain normal cell functions through the production of key proteins (L-selectin and interleukins) and cell surface receptors.

Research in the area of stress and immunity has shown that many components of the innate and adaptive immune systems are compromised during periods of stress. In particular, hormonal changes around the time of calving (figure 1.) can alter the ability of innate immune cells to respond and kill mastitis causing pathogens, through the inhibition of the production of L-selectin which is vital for normal neutrophil function (figure 2.). The detrimental effects of stress on immune function is not limited to those associated with parturition but can occur at any time and because of this it is important to initiate management and nutritional programs to reduce these events so cows are better to withstand pathogen challenges and maintain productivity.

Innate Immunity

The innate immune system represents the cow’s first line of defense against a pathogen challenge and provides the adaptive system the time required to develop the appropriate antibody response. Several components comprise the innate system, and they present barriers to pathogen entry and infection. These barriers consist of: 1) physical (skin, tears, gut and mammary cells); 2) chemical (stomach acid); 3) enzymatic (digestive); and 4) blood cellular components.

Neutrophils: “First Line of Defense”

Granulocytes and macrophages are predominantly white blood cells involved in innate immunity. Granulocytes are also called polymorphonuclear leukocytes (PMN), which are a diverse collection of white blood cells, including neutrophils. In the adult cow, there are approximately 200 billion neutrophils, half in circulation and the other half either attached to vessel walls or stored in bone. The life span of a neutrophil is short — 8 to 24 hours — and these white blood cells go through a process of self- destruction called apoptosis.

Figure 3. Toll-like receptors in cells. Eleven toll-like receptors have been identified and each
binds to a specific PAMP. Toll-like receptors 2 and 4 are responsible for identifying common molds as foreign.

The main function of neutrophils is to monitor for sites of infection and kill pathogens. Neutrophils identify pathogens by the recognition of distinct pathogen-associated molecular patterns (PAMPs). Specifically, pathogens contain molecules not typically found in mammalian cells and via this recognition of PAMPs neutrophils are able to find foreign cells. Examples of molecules associated with pathogens and recognized by neutrophils include lipotechoic acids, double-stranded RNA, CpG DNA sequences, and unusual sugar residues.

The neutrophil detects PAMPs by using specific receptors, called Toll-like receptors, which are located on their outer surface (Figure 3). Binding of PAMPs to Toll-like receptors initiates the killing mechanisms of neutrophils of which there are several. These include engulfing pathogens (phagocytosis), or entrapping them using projected strands of DNA called neutrophil extracellular traps or NETS and by respiratory bursts that involve the generation of several reactive oxygen species (ROS) which are bactericidal.

Adaptive or Antibody-Mediated Immunity

The primary function of the adaptive immune system is to develop antibodies against specific antigens. The time required for this response can be variable, ranging from a few days to several months, depending upon the antigen and the health of the cow. The antibodies produced in response to a foreign protein or antigen can be derived from a variety of cell types: T- and B-lymphocytes, antigen-presenting cells and Natural Killer (NK) cells.

Antibody Expressing Cells

B-cells mature in bone marrow (hence the name “B”) and are released into blood where they circulate and are captured by lymphoid tissue. These cells live less than 48 hours, unless they interact with their antigen (trigger activation), resulting in their proliferation and differentiation, a process termed “clonal selection.” The type of B-cell that can mature is driven by a process of “random gene rearrangement,” which can result in approximately 108 different types of B-cells, each with a specific target antigen.

Proliferation of a B-cell antigen-specific lineage is initiated following interaction with the antigen and requires input of interleukins-2, -4, -5, -6 and IFNy from T-helper cells. These cytokines cause formation of B memory cells from the activated B-cell population. Memory B cells can secrete as many as 2,000 antibody molecules/second into plasma. Antibodies may be of a variety of forms (e.g., IgG, IgM), which are targeted for specific purposes in the fight against pathogens. T-cells are manufactured in bone marrow and mature in the Thymus (hence the name “T”-cell). T-cells are responsible for “cell-mediated immunity” because the antibodies they manufacture remain attached (tethered) to the surfaces of the T-cell population. As in B-cells, interaction of a T-cell with a specific antigen causes clonal selection and expansion of a specific T-cell population that express as many as 100,000 antibody molecules on the surface of each cell. Clonal selection of T-cells, as with B-cells, leads to the development of “memory T-cells” (figure 5).


Antibodies consist of a Y-shaped molecule, containing a constant (C) region and a variable (V) region. If antibodies are destined to become tethered to the surface of a T-cell membrane (see Figure 6), they are expressed with a transmembrane domain which allows for interaction with membranes. If antibodies are destined to be secreted, the C-terminus of the antibody molecule is assembled lacking a transmembrane domain structure. For both the tethered and secreted forms of antibodies, the variable region (i.e., the fork of the “Y” domain) represents the strategy which animals use to specifically target a unique antigen.

Whether antibodies are tethered or secreted, the constant region may be assembled from distinct genes that in turn yield different antibody isotopes, such as IgG, IgM, IgD, IgA and IgE. Each of these isotopes has different physical properties and different functions in the animal’s body. IgM is the first immunoglobulin isotope to be expressed during B-cell development, and although IgM is an early responder, it has a low affinity against antigen compared to the IgG isotopes. IgG antibodies consist of four subclasses — IgG1, IgG2, IgG3 and IgG4 — and are named in order of abundance in serum.

Relationship of the Innate and Acquired Immune Systems

Initially it was thought that the innate and acquired immune systems functioned independently. However, it is now known that these two arms communicate with one another, and to some extent, rely on similar communication molecules such as interleukin 1B. This molecule, for example, is released by neutrophils when activated by invading pathogens. This stimulates the acquired immune system as a feed- forward system to start the process for antibody production.


The immune system provides protection from infections and disease-causing organisms. First and immediate response to pathogens is the responsibility of a specific group of white blood cells (macrophages and neutrophils) that comprise a portion of the innate immune system. These leucocytes continually monitor for sites of infection and provide protection until the cow can mount an antibody response.

The adaptive or antibody mediated immune system, which is a pathogen- specific immune response, involves the formation of antibodies. T- and B-cells are cells of the adaptive immune system responsible for the production of antibodies that provide long-term protection against numerous types of pathogens and other disease-causing agents.

A Cow’s Healthy Immune System Starts with Good Nutrition

Good herd health starts with good nutrition, and good nutrition is required to help maintain
a healthy immune system in dairy cows.

When cows are under stress from the strains of production and reproduction, or molds
and mycotoxins in feed and pathogens in the environment, their natural immune system goes to work fighting off those challenges. In an ongoing fight, the cow’s immune system itself can begin to weaken.

That’s why good nutrition is so important, including sufficient energy, fiber, vitamins, trace minerals and the special nutritional supplements your nutritionist or veterinarian may recommend.

Figure 3. Toll-like receptors in cells. Eleven toll-like receptors have been identified and each
binds to a specific PAMP. Toll-like receptors 2 and 4 are responsible for identifying common molds as foreign.

Figure 4. Neutrophil migration/phagocytosis (Janeway, 2005, pg 13)

Figure 5. Cellular interactions involved in induction of immune responses. Activation and proliferation of TII cells (a) is required for generation of a humoral response (b) and a cell response to altered self-cells (c). APC = antigen- presenting cell; Ag = antigen.

Figure 6. Antibody configuration (Janeway 2005, pg 17, figure 1.16)

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