Influence of nutrition on immune status of the bird

Doug Korver ¹ and Kirk Klasing ²

1 Department of Agricultural, Food and Nutritional Sciences, 4–10 Agriculture/Forestry Centre, University of Alberta, Edmonton, AB T6G2P5, Canada

2 Department of Animal Science, Meyer Hall, University of California, Davis, Davis,CA 95616, USA

Proceedings of the 24th Technical Turkey Conference p43

Introduction

Nutrients play an important role in the protection of the host against invading pathogens. Nutrient deficiencies can affect immune function, usually in a negative manner. Certain nutrients are capable of modulating the function of the immune system through a variety of mechanisms. This paper will discuss the impact that nutrients have on immune function, and the effect of an immune system response on the nutritional status and needs of the animal.

Nutritional Modulation of Immune Function

Development of the immune system

Nutrients are required to provide the building blocks for immune cells and tissues. This includes non-specific mechanisms such as the skin, which presents a physical

barrier to pathogens, as well as cells such as T and B lymphocytes, macrophages, and natural killer cells. Several nutrients are especially important in early development of the immune system. Vitamin A levels necessary to maximize immunocompetence have been shown to be much higher than that needed for optimum growth and feed efficiency (Sklan et al., 1994; Friedman and Sklan, 1997). Other nutrients which can affect early immune development are linoleic acid, iron, selenium and some of the B vitamins (Klasing, 1998). Much of the development of immune tissues occurs late

in incubation and the early part of life. Therefore, maternal nutritional status and deposition of nutrients, as well as early nutrition play an important role in this means of nutritional immune system modulation.

Substrate supply

Although the response to an infectious challenge is a highly complex event requiring scores of modulators and messengers, the actual amount of material used in the

immune response may be quite low. Leukocytes have been calculated to make up approximately 0.42% of the body mass of a chicken, and the total amount of antibody present in the body is less than 0.1% of body weight, even in the event of antibody production in response to a challenge (Klasing, 1998). Much of the demand for nutrients during an infection come as a result not of nutrient demand by

leukocytes, but from the acute phase response. This response occurs shortly after exposure to an immunogen, and is characterized by synthesis of acute phase proteins by the liver, fever, and increased whole-body protein turnover and hepatic gluconeogenesis (Grimble, 1996; 1998; Moldawer and Copeland, 1997).

Nutritional immunity

Nutritional immunity refers to redistribution of certain nutrients within the body of the host to limit the availability of these to invading pathogens. The efficacy of this

strategy is shown by studies in which increasing plasma iron concentrations increases mortality following an Escherichia coli challenge (Tufft and Nockels, 1991). As part of the acute phase response, iron and zinc are removed from circulation and stores in the liver and extrahepatic tissues, limiting their availability to pathogens.

Hormonal milieu Immune cells have receptors for a wide variety of hormones regulated by diet, including insulin, insulin-like growth factors, glucagon, thyroxin, catecholamines and corticosterone (Klasing, 1998). Improvements in both cell-mediated and antibody responses have been shown in chicks following a brief period (12-24 h) of feed deprivation. Longer-term feed restriction tends to impair antibody and cell-mediated responses.

Regulatory actions of nutrients

The complexity of the immune response requires vast numbers of molecules communication. Ultimately, these mediators are derived from the nutrients ingested by the host. Some of the mediators, particularly those derived from dietary fatty acids can have altered potency based on the precursor molecule. The eicosanoids are derived from 20-carbon polyunsaturated fatty acids. Those derived from the n-6 family of polyunsaturated fatty acids (PUFA) are much more potent in their pro-inflammatory actions than those derived from the n-3 family of PUFA. The feeding

of diets enriched in n-3 PUFA dramatically decrease the inflammatory response to Eimeria tenella (Korver et al., 1997; 1998). Vitamins A, D, and E all have regulatory

roles in the immune system (Cook, 1991).

Reduction of pathology

Activation of cellular components of the immune system result in the release of destructive molecules into the microenvironment. These molecules are used by the body to kill invading pathogens, but can also be damaging to the host tissues. Many of these molecules are oxygen-based, and are referred to as reactive oxygen species (ROS). Vitamins E and C work together as antioxidants to protect cells from damage by the ROS. Dietary cysteine is incorporated into the antioxidant glutathione, and dietary sulfur-amino acid deficiency can have a pro-oxidant effect in vivo (Grimble, 1996; 1998). By increasing the ability of the host to protect itself against the ROS, a more intense response to pathogens may be allowed.

Physical/chemical actions in GI tract

The contents of the gastrointestinal tract include not only ingested nutrients, but a large volume of bacteria, both pathogenic and nonpathogenic. The body must maintain a balance between excluding the bacteria, and allowing absorption of nutrients from the GI tract. The physical nature of the diet can impact the integrity of the barrier between the lumen of the intestine and the animal. Chemical composition can alter bacterial populations by increasing digesta viscosity or by providing nutrients which are preferentially used by certain bacteria.

Effect of Feed Restriction and Specific Nutrients on Immune Function

Through the mechanisms discussed earlier, specific nutrients can impact, positively or negatively, the immune response of an animal.

Feed Restriction

Short-term feed restriction (12-24h) can enhance the response of birds to a vaccination relative to fasted or ad libitum-fed birds (Cook, 1991). Longer periods of

restriction or fasting can have a deleterious effects on the immune response, associated with increasing levels of corticosterone.

Energy

Energy restriction of birds has a varying effect on immune function, depending on the level of other nutrients in the diet. When chicks were fed a calorie- and amino acid-deficient diet, antibody responses were equal to that of control chicks fed an adequate diet. Over-consumption of amino acids due to feeding a calorie-deficient, amino acid-sufficient diet was associated with decreased antibody responses (Cook, 1991).

Carbohydrates

Benson et al. (1993) reported that at equal dietary energy levels, corn starch decreased the growth-suppressive effects of lipoplysaccharide injection of chicks relative to diets containing corn oil. Part of this effect may be due to the pro-inflammatory effects of diets high in n-6 PUFA.

Lipids

The fatty acid composition of the diet can have a dramatic effect on the specific (Fritsche et al., 1991), and the inflammatory (Korver et al., 1997, 1998) aspects of the immune response. These actions are mediated largely through the activity of eicosanoids, which are metabolites of 20-carbon polyunsaturated fatty acids. When certain eicosanoids are derived from n-3 PUFA (eg. Prostaglandin E3 and leukotriene B5), they have much lower potencies as pro-inflammatory mediators than do the corresponding eicosanoids derived from n-6 PUFA (eg. prostaglandin E2 and leukotriene B4). The eicosanoids can affect both the release of pro-inflammatory cytokines from effector cells such as macrophages, as well as the effect of those cytokines at the level of the target tissues. Therefore, the n-3 PUFA tend to have an anti-inflammatory effect, while the n-6 PUFA tend to have a pro-inflammatory effect.

Vitamins

The effect of vitamin A on immune function was discussed earlier. Vitamin E can exert an anti-inflammatory effect by decreasing the production of prostaglandin by activated leukocytes. Peripheral blood monocytes have a receptor for 1,25 dihydroxycholecalciferol, and may be associated with decreased IL-1 activity (Cook, 1991). Water-soluble vitamins are also involved in immune responses. Vitamin C is intimately involved in the regeneration of functional vitamin E after that vitamin has

quenched free-radical reactions, thus allowing the protection of the host against ROS. Vitamin B6, although not an antioxidant, plays an important role in antioxidant

defence by virtue of its metabolic role in the formation of cysteine, which is the rate-limiting precursor in the formation of glutathione (Grimble, 1998).

Minerals

Copper deficiency can decrease antibody response, mitogen-induced blastogenesis and mixed-lymphocyte reactions in mice, and addition of copper to poultry diets

increased primary antibody response. Zinc deficiency also has been demonstrated to suppress immune functions in mammals and poultry (Cook, 1991).

Protein and Amino Acids

Chicks fed diets low in essential amino acids had decreased delayed-type hypersensitivity and secondary IgG responses relative to chicks fed adequate diets, although this effect may have been due to amino acid imbalances rather than a

deficiency per se (Cook, 1991). Specific amino acids in general tend to decrease humoral response, while having a lesser effect on cellular immunity. Total sulfur amino acid (TSAA) deficiency may limit the availability of cysteine for production of glutathione, and therefore limit antioxidant defenses against ROS produced during an immune response. Results of studies in which deficiencies in TSAA were caused have had mixed results. Bhargave et al., (1970) found that a methionine deficiency resulted in increased antibody levels, while Tsiagbe et al. (1987) suggested that the requirement for methionine for maximum antibody titres was greater than that for growth. Discrepancies in these results may be the result of differing experimental designs and antigens used.

Impact of an Immune Response on Nutrition

The immune response can be divided into two basic components. There are non-specific defenses, which protect the host by excluding pathogens, or by creating conditions within the host which provide an inhospitable environment for a wide range of pathogens. Barriers to entry and survival of pathogens include the skin, the mucus coat of the GI tract, and molecules such as agglutinins, precipitins, acute-phase proteins, lysozyme, etc. These mechanisms act non-specifically in that they are not targeted against a specific pathogen; many different pathogens can induce similar responses. Once a pathogen has gained entry to the host, the initial response is an inflammatory response. Because this response is non-specific, the effects are often systemic within the host, and can have effects throughout the body. Fever, cachexia, and anorexia are all examples of byproducts of the inflammatory response which have systemic effects. Cells involved in the non-specific response include

natural killer cells, and pro-inflammatory cells such as marcophages, monocytes and neutrophils or heterophils. The inflammatory response results in a series of behavioral, immunologic, vascular and metabolic responses. The sum of these responses results in slowed growth rate, the loss of skeletal muscle, decreased appetite, morbidity and possibly mortality. The mortality is often due to the effects of the mediators of inflammation produced by the host, rather than the pathogen itself. This is evidenced by the use of bacterial lipopolysaccharide (LPS) to induce an inflammatory response. In this model, bacterial cell wall components mimic the effects of bacterial infection, even though the LPS is sterile. The host recognizes the LPS as being foreign, and mounts an inflammatory response, even though not responding would have no deleterious effect on the host. The inflammatory

response can result in dramatic decreases in productivity of animals; antibiotics appear to work by minimizing the necessity of the inflammatory response to deal with bacteria (Roura et al., 1992). Following an inflammatory response, animals may undergo compensatory growth. During this time, nutrient needs of the animal may be increased. The second aspect of the immune response is the specific immune response, in which very specific molecules such as immunoglobulins are produced to respond to a very specific antigen. The specific defenses employed by the host include the humoral response (Immunoglobulins from B cells) and the cellular response (T-cell mediated). This response is much more focused, and therefore the action of the immune system does not tend to have a large direct effect on the host in terms of nutrition. As discussed previously, the nutrient needs of the cell types involved in specific responses are minimal compared to the alterations in metabolism and demand associated with an inflammatory response. Much research in the area of

nutrition-immune function interactions is aimed at modulating immune responses to such that specific immunity, rather than inflammation is the predominant response.

Summary

Through a number of mechanisms, dietary components can have direct and indirect implications on the intensity and efficacy of immune responses. Some nutrients are capable of increasing immune responses, others are capable of decreasing immune responses. An appropriate immune response is not always the most vigorous one;

inappropriate (e.g. autoimmunity), excessive (e.g. inflammatory responses to non-pathogens) or inadequate (e. g. low antibody response to viral challenge) are all

examples of cases in which the immune system can let the host down. An appropriate balance among the various components is necessary to ensure host survival and ability to recover from the challenge.

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