
With high density confinement
rearing of birds, an additional important role of poultry nutrition is that
birds are not only fed for production or reproductive performances but must
also be fed to minimize infectious disease and their concomitant stresses. In
context of poultry nutrition Industry, problem of immune-suppression has been
felt to be prominent due to various factors viz. managemental conditions and
intensive production system, high density rearing and infectious diseases.
Therefore, it is highly essential to find ways and means for enhancement of
immune response by nutritional intervention. Substantial information is
available in literature to indicate that administration of certain vitamins,
minerals, amino acids and their different combinations to mammals and chicken
in excess of their supposed requirements enhances their disease resistance.
This increased resistance has been attributed to significant stimulation of
humoral and cellular immunity and phagocytosis. Since, the use of antibiotics
has been limited, better use of immuno-stimulatory has to be made in the poultry
feed supplement.
The immune system of birds benefits
greatly from proper poultry nutrition. Not only does the immune system benefit
directly from proper poultry nutrition, but indirectly proper poultry nutrition
will also prepare the bird for periods of stress, reducing the adverse effects
of stress and enhancing recovery from stressful periods. Therefore, in many
instances, immune suppression is associated with the stress response in the
bird. In animal nutrition the immune system of the bird can be influenced by  in several ways;
1. Anatomical development of
lymphoid tissues
2. Mucus production
3. Synthesis of immunologically
active substances
4. Cellular proliferation
5. Cellular activation and
movement
6. Intracellular killing of
pathogens
7. Modulation and regulation of
the immune process
Factors related to the genetics
of poultry and poultry nutrition, the frequency of their exposure to pathogens,
the virulence of the pathogens, and the efficacy of vaccination programs are
predominant detriments of the incidence of infectious diseases in poultry
flocks. However poultry feed supplement and diet characteristics can modulate a
bird's susceptibility to infectious challenges and subtle influences due to the
types of ingredients used and assumes critical importance. The bird's
susceptibility to an infectious challenge can be subdivided into two
components, resistance and resilience.
Resistance refers to the capacity
of a variety of anatomical and physiological systems, including the immune
system, to exclude pathogens.
Resilience refers to the capacity
of the bird to maintain productivity (e.g. growth, feed efficiency, egg
production) during an infectious challenge.
The role of poultry nutrition in
maximizing resilience is only now being appreciated and this relationship
deserves future attention by poultry feed supplement stake holders. There are
probably many situations in which diets that optimize resistance to infectious
challenges are not optimal for resilience and maximal profitability (Cook,
1996;
Klasing, 1997). However, in many
cases it is not known whether the requirement values that maximize productivity
in healthy, unchallenged birds are optimal for immuno-competence and disease
resistance. An understanding of the mechanisms through which poultry nutrition influences
the immune system is necessary to appreciate the many complex interactions
between! diet and infectious diseases. Several recent reviews of poultry
nutrition and immunity provide an excellent survey of poultry nutrition and
immunity, including the impact of toxic components (mycotoxins) that may
contaminate the feed (Cook, 1991, 1996; Latshaw, 1991: Dietert et al., 1994).
Mechanisms of Modulation of
Resistance
In animal nutrition the
mechanisms of modulation of resistance to infectious disease are divided into
seven categories. Obviously these categories are overlapping and nonexclusive: single
factor may impact the immune system by several of the general mechanisms that
are described as well as mechanisms not listed. The first six of these
mechanisms relate to the effect of poultry nutrition on the immune system,
whereas the last mechanism considers several non-immunological aspects of the
diet. The first three categories consider the role of poultry nutrition as
substrates for the replication and function of cells. A substrate role is
necessary for the initial development of the immune cells. and tissues
(Mechanism 1) and during an actual immune response so that responding cells can
divide and synthesize and their supply is contraindicated during an infection
(Mechanism 3). Though diet may influence processes important to immunity by
providing building blocks (substrates) for the construction of cells and
molecules, other mechanisms may be even more important for dietary modulation
of the immune system in animal nutrition. These include direct regulatory
actions on the leukocytes that respond to infectious challenges (Mechanism 4),
as well as indirect effects that are mediated by poultry nutrition modulation
of the classical endocrine system (Mechanism 5). Furthermore, poultry nutrition
may impact the level of pathology resulting from the killing pathways of the
immune system (Mechanism 6).
Impact on the Development of the
Immune System
The developmental events
important for immune competence begin in the embryo and continue during the
1" week following hatching (Gobel, 1996; Ratcliffe et al., 1996). The
1" week of life is a period of rapid expansion of leukocyte populations,
seeding of lymphoid organs, and educational events that produce the unique
clones of lymphocytes that will mediate immunity later in life. It is not
surprising that this is a critical period during which poultry nutrition deficiencies
or excesses may impact the immune system. In general, chronically severe
deficiencies of micro-poultry nutrition are more debilitating to the
development of the immune system than macro-poultry nutrition such as energy
and protein. Poultry nutrition deficiencies that are especially damaging to
development of the immune system include linoleic acid, vitamin A, iron,
selenium, and several of the B vitamins (Cook 1991; Latshaw, 1991: Dietert et
al., 1994).
Embryonic development of the
chick is known to be very sensitive to vitamin A deficiencies and it has been
known for many years that chicks hatched from vitamin A-deficient hens have
impaired immunity and decreased resistance to a wide variety of infectious
diseases. In poultry nutrition the level of vitamin A that maximizes growth and
feed efficiency of broiler chickens (500 mg/kg) is insufficient for optimal
development of the immune system. The level needed for maximal growth and
efficiency in clean University facilities was used to set the NRC requirement,
yet an amount that is 10-to 20-fold higher is necessary to maximize immuno
competence of the young broiler chick (Sklan et al., 1994; Friedman and Sklan,
1997). However, excess of vitamin A can also impair immuno-competence, probably
by causing secondary deficiencies of other fat soluble vitamins (Veltman et
al., 1984; Friedman and Sklan, 1997).
Micronutrient of the hatchling is
very dependent upon the poultry nutrition given of the laying bird (Naber and
Squires, 1993). The level of stores of most of the vitamins and trace minerals
in the hatchling are highly correlated with the level in the breeder's diet.
Sufficient stores may completely buffer the young chick against severe
deficiencies during the critical early weeks when the immune system and the
intestines develop. Thus, the role of on the developmental events of the immune
system must consider the diet of the hen as well as the diet of the chick.
Substrate Supply
Defense against an infectious
challenge requires a highly integrated response by the immune system. From a poultry
nutrition viewpoint, substrates (e.g. amino acids, energy, enzyme co-factors)
are needed to support the clonal proliferation of antigen-driven lymphocytes,
the recruitment of new monocytes and heterophils from bone marrow, the
synthesis of effector molecules (e.g. immunoglobulins, nitric oxide, lysozyme,
complement), and communication molecules (e.g. eicosanoids, cytokines). A
quantitative summation of the poultry nutrition along with poultry feed
supplement  costs of maintaining the
immune system and the additional costs of a vigorous immune response against a
challenge is not known for any species.
Though the rate of synthesis of
specific immunoglobulins increases dramatically during a disease challenge, the
rate of synthesis of total immunoglobulins increases only moderately.
Hyperimmunization, for example, results in about a 25% increase in serum
immunoglobulin (Leslie and Clem, 1970). Based on serum concentrations and half-
life estimates, other humoral components contribute an order of magnitude less
to daily synthesis than do immunoglobulins. This analysis of the size of the
immune system and rates of its processes suffers from the use of cross-species
data and lacks attention to specific issuesthat may be concentrated in
leukocytes or preferentially utilized by them (e.g.. Arginine and Glutamine).
Even with these qualifications in mind, it is apparent that the amount of
substrate resources including that of poultry feed supplements needed by the
immune system is very low relative to needs for growth or egg production.
For example, the weight of new
leukocytes and immunoglobulins normally produced each day (about 800 mg/kg body
weight) appears to be less than 1% of the total increase in body weight of a
2-wk-old broiler chick and less than 10% of the amount of breast. Muscle
synthesized each day. Even if an infectious challenge increases the rate of
leukopoiesis by considerably more than the twofold estimates that have been
reported, it is doubtful that the immune system would be a significant consumer
of poultry feed supplements. It is often stated that the depression in
performance that is associated with an immune response is due to the diversion fom
growth or egg production to be used by the immune system. Given the above
quantitative analysis, this statement cannot be true. However in animal
nutrition , the immune system is not the only system that increases use during
an infectious challenge. Many infections are accompanied by an acute phase
response, which is characterized by the synthesis of acute phase proteins,
fever, accelerated whole-body protein turnover, and high rates of hepatic
gluconeogenesis. The acute phase response includes changes in metabolism and poultry
nutrition fluxes in all organ systems of the body, especially liver and muscle.
Although descriptive information on the acute phase response of chickens has
been detailed (Klasing and Johnstone, 1991) the poultry nutrition demands of
this response are not well described. Clearly the acute phase response is a
process that is both poultry nutrition liberating (skeletal muscle catabolism)
and poultry nutrition consuming (acute phase protein synthesis, fever). Given
the marked increase in hepatic demand for amino acids to support
gluconeogenesis and for acute phase protein synthesis, it is likely that the
amino acid costs of an acute phase response are considerably greater than the
relatively minute needs of leukocytes that respond to an infectious challenge
(i.e. the immune response) For several poultry nutrition  elements (e.g. zinc, iron, copper, lysine), it
is known that the amount liberated is sufficient to meet the needs of both
acute phase and the immune responses. Given that the acute phase response is
likely to be a much larger consumer of during an infectious challenge than the
immune system itself, future studies on the impact of poultry feed supplement should
include measures of the adequacy acute phase response, such as production of
acute phase proteins.
Animal nutrition and nutritional Immunity
The immune system coordinates a
rapid flux of several poultry nutritional ingredients out of body fluids and
into intracellular storage pools starving some types of pathogens. For example,
transferring production by the liver increases dramatically during the acute
phase response of broiler chickens and laying hens (Hallquist and Klasing,
1994). This iron binding protein mediates the transfer of iron out of blood
plasma and into the liver where it is less available to pathogens. Feeding high
levels of EDTA to chicks increases the deposition of iron into tissues and
increases plasma concentrations. This predisposeschicks to increased mortality
following a challenge with Escherichia coli (Tufft and Nockels, 1991). A
redistribution of zinc is mediated by interleukin (IL)-1 during the acute phase
response, due to enhanced synthesis of hepatic metallothionein (Klasing, 1984),
however it is not clear if this is important in limiting the availability to
pathogens in animal nutrition. Avidin is secreted by stimulated chicken
macrophages, suggesting that the sequestration of blotin aids in starving
pathogens of biotin at the site of infections (Korpela, 1984).
Direct Regulatory Actions
An immune response requires
extensive communication between a wide variety of cell types. They play
important roles by modulating the release of communication molecules or by
changing the reactivity of leukocytes to extracellular signals. Amongst poultry
feed supplements polyunsaturated fatty acids (PUFA) provide a good influence in
the immune system by affecting intercellular communication. The amount, type, and
PUFA determines the types of fatty acids that are incorporated into cell
membranes and consequently the fluidity of the membrane and the types of
eicosanoids that are released as communication molecules (Korver and Klasing,
1995, 1997). Linoleic acid is a member of the n-6 series of PUFA and a
principle fatty acid in cereal grains and soybeans. It is elongated to
Arachidonic acid and incorporated into cell membranes, A
phospholipase-dependent communication cascade causes the release of
arachidonate and its conversion into metabolically active prostaglandins,
leukotrienes, and thromboxanes. Similarly, in poultry nutrition n-3 PUFA can be
incorporated into cell membranes. Upon release during cell signaling, the n-3
PUFA modify the amounts and types of eicosanoids that are produced causing
changes in cell communication. In broiler chickens dietary fish oil, which is
high in n-3 PUFA. modulates IL-1 and prostaglandin E (PGE) release during an
inflammatory response. The modulatory effects of poultry nutrition in dietary
n-3 fatty acids are reflected in increases in antibody responses to antigens
but decreases in mitogen-induced proliferation of lymphocytes (Fritsche et al.,
1991; Korver and Klasing 1997).
Physical and Chemical actions of
Feeds
Feed accounts for 65-70% of the
total costs in animal nutrition and production. Any operation must therefore
have clear targets how to optimize feed efficiency and reduce feed cost and
work daily towards those targets. The sharp rise in feed ingredient prices in
general, and soy bean meal in particular has forced producers to refocus on
what they spend on feeding, to raise efficiency targets and to go the extra
mile for converting feed protein more efficiently into lean gain.
There exists a relation between
dietary poultry feed supplements concentration and feed cost, performance and
revenue. Both revenue and feed cost increase with higher poultry nutrition density
in the diet (Waller, 2007). Thegreen zone marks the area with maximal
difference between the revenue curve and feed cost curve. When setting the poultry
nutrition levels in this range, the margin for 'revenue over feed cost' is highest.
As feeding cost is a major production issue, this is also likely to represent
the area with maximal net profit. A consistent production system with accurate
data on animal nutrition and performance and carcass value are needed to fine
tune the system. This basic information is available in most broiler
operations, as bird genetics and the overall production system are well
standardized. Many swine fattening farms also have such data available to
define the poultry nutrition concentrations which are most suited for their
genetics and the market conditions they operate under.
The intestines are the primary
battleground between potential pathogens and the immune system. This is
evidenced by the large number of pathogenic and nonpathogenic organisms located
in the intestinal lumen (15 x 10"/kg body weight, Roitt, 1997), the
focusing of host defenses along the intestinal epithelium (.e. the
gut-associated lymphoid tissue). and the high incidence of entero-pathogenic
diseases in all animals. The intestinal epithelium must maintain exceptionally
high physical integrity to prevent the bulk transport of pathogens into the
body, but it must be sufficiently thin to actively transport poultry nutrition.
Physical and chemical attributes of the diet can modify the populations of
microorganisms in the gastrointestinal tract, the capacity of pathogens to
attach to enterocytes, and the integrity of the delicate intestinal epithelium.
Role of trace minerals in
immunomodulation
A deficiency in one or more of
these elements can compromise immunocompetence of an animal nutrition (Beisel,
1982; Suttle and Jones, 1989). The trace metals that have been associated with
an improvement in immunity, or functions that support immunity, are Zinc,
Manganese, Copper, and Selenium. The first level of defense in the immune
system is the skin. Zinc and manganese are key elements for maintaining
epithelial tissue integrity.
Zinc plays an important role in animal
nutrition, particularly for layers, as a component of a number of metallo
enzymes such as carbonic anhydrase which is essential for eggshell formation in
the hen's shell gland. Other important zinc metalloenzymes in the hen include
carboxypeptidases and DNA polymerases. These enzymes play important roles in
the bird
immune response, in skin and
wound healing, and for hormone production (testosterone and corticosteroids),
Classic deficiency symptoms of a zinc deficiency in poultry nutrition could
include a suppressed immune system, poor feathering and dermatitis, infertility
and poor shell quality.
Selenium is an important
constituent of the enzyme glutathione peroxidase. Glutathione peroxidase
functions in the cell as its first line of defence against oxidation. Other
selenoproteins in poultry nutrition play an important role in prevention of
exudative diathesis, normal pancreatic function, and fertility. Levels of
selenium as poultry feed supplement are limited by the FDA to only 0.30 ppm.
Levels of selenium in feedstuffs for poultry nutrition can vary considerably
dependent on soil content of selenium the crops are grown on. Often times,
total selenium would reach levels of 0.40 to 0.50 ppm when corn and soybean
levels are combined with 0.30 ppm levels. These high levels can to be
beneficial to the immune status and performance of poultry flocks without being
toxic. Dietary selenium works with Vitamin E in boosting the immune status in poultry
nutrition.
Role of trace minerals in immuno
modulation (Swine)
Trace minerals such as manganese,
iron and zinc are essential for swine mineral as they are involved in many
digestive, physiological and biological processes that directly affect
fertility and health of sows and newborn pigs, and carcass quality of fattening
pigs. When trace minerals are not provided in the proper levels, digestion. Immune
system, hormone production, bone integrity and skin health can be seriously
affected.
Several minerals are included in
the regulation of the pig's immune system. The role of selenium in protecting
biological membranes from oxidative degeneration was established many years ago
(Lessard et al., 1991; Oldfield, 2003).
In animal nutrition dietary selenium
is, therefore, necessary to obtain maximal immunity in pigs, but to avoid
toxicity due to over the inclusion of selenium in diets fed to livestock is
regulated by FDA and cannot exceed 0.3 ppm. However, recent research indicates
that organic sources of selenium are better utilized by pigs than inorganic
sources (Mahan and Parrett, 1996: Mahan et al., 1999). As a consequence, to
obtain maximum improvements in the immune system, it may be advisable to use
organic selenium, rather than inorganic sources of selenium.
Copper sulfate is usually added
to nursery diets at concentrations between 150 and 250 ppm, although the poultry
nutrition requirement for copper is much lower. Likewise, zinc oxide is often
added to starter diets at levels of 2,000-4,000 ppm, which is much higher than
the poultry nutrition requirement for zinc. However, the inclusion of these
minerals at high concentrations in diets fed to nursery pigs has been shown to
reduce scouring and to control post-weaning diarrhea without causing any
toxicity symptoms (Poulsen, 1995; Goransson, 1997). These effects may be caused
by the ability of zinc and copper to reduce concentrationsof coliform bacteria in
the intestinal tract of weanling pigs (Namkung et al., 2006).
Role of vitamins in
immunomodulation
Vitamin A: Low and very high poultry
nutrition dietary vitamin A decreases body weight gain in broilers. Low poultry
nutrition dietary vitamin A causes depression in vitro T-Lymphocytes responses
and in vitro antibody production to defined protein antigens. Excess vitamin A
intake also decreases immune responses. Maximum T-cell proliferative responses
to antigen have been observed at vitamin A levels considerably above NRC (1984)
recommended level. Vitamin A is required for intestinal absorption of zinc (Zn)
in poultry nutrition while zinc influences vitamin A utilization by affecting
retinol binding protein (RBP) synthesis and release from liver.
.
Following primary immunization,
the chickens deficient in vitamin A show the lowest antibody liter. The
difference in antibody titer is the maximum on 7" day post-immunization. The
supplementation in poultry feed supplement of Vitamin A either on the day of
vaccination or few days afterwardsincreased antibody titer. It has been
demonstrated that the optimum Hi titer against Newcastle disease was obtained
when the feed contained 20,000 1.U. Vitamin A per kg of feed.
.
Vitamin C: Under normal
conditions, Vitamin C (Ascorbic acid) is synthesized in sufficient amounts by
all species of poultry. However, under prolonged exposure to stress the
ascorbic acid utilization may exceed the ability of chicken and turkeys to
synthesize ascorbic acid. It is observed that ascorbic acid poultry feed
supplement increases the HA level from 4 to 6 days post vaccination. The
mechanism by which ascorbic acid ameliorates steroid mediated
immuno-suppression is either by reducing adrenal synthesis of corticoids or by
protecting the lymphoid tissues.
Vitamin D: Vitamin D is critical
for proper bone development in poultry and enhancing poultry nutrition.
Research has elucidated negative effects on broiler cellular immunity as
affected by vitamin D deficiency (Aslam et al. 1998). In female broilers a diet
devoid of vitamin D or a diet containing 800 IU/kg of cholecalciferol had
depressed cellular immunity as measured by cutaneous basophil hypersensitivity
response to phytohemagglutinin-P, depressed thymus weight, and depressed
macrophage function. However, although SRBC is a T-dependent antigen,
differences in primary or secondary responses did not occur (Aslam et al.,
1998). Bio-chemical relationships. The supplementation of Vitamin E as poultry
feed supplement in the diet of chicks enhances humoral immunity, which may be
due to destruction of peroxides by vitamin E. Vitamin E and Se play a role in
protecting against oxidative damage. Free radicals are scavenged by vitamin E
as a first line of defense and then glutathione peroxidase of which Se is a
part destroys any peroxides formed before they can damage the cell.
Vitamin E: Vitamin E enhances
specific humoral and cell mediated immune responses as well as native
resistance to disease, particularly phagocytosis levels of vitamin E have an
immuno stimulatory effect, increase delayed hypersensitivity and affect
mitogenic responsiveness. The Poultry feed supplement of Selenium at levels
above those recommended as requirements (0.1 ppm) enhances the primary immune
responses. Vitamin E and Se appear to participate in similar poultry nutrition and
accordingly studies have been conducted with various levels of Se, vitamin E
and their combinations to examine the effect on performance and immune response
of broilers. Effect of poultry feed supplement of vitamin E, selenium and their
combinations suggested that maximum body weight gain and best efficiency of
feed utilization were observed in broilers fed diets containing 0.50 mg/kg Se
and 300 IU/kg vitamin E Significantly higher antibody titres (HI and ELISA) at
10 day PI were attributed to 0.06 mg/kg and 150 IU/kg Se and vitamin E
respectively. Hence, optimum growth and immune response may be achieved at  level of Se of 0.06 mg/kg and vitamin E at 150
IU/kg. The vitamin E level is higher than that recommended by NRC (1984, 1994),
Role of AA in immunomodulation
In animal nutrition Amino acids
are required for the synthesis of a variety of specific proteins (including
cytokines and antibodies) and regulate key metabolic pathways of the immune
response to infectious pathogens. Adequate dietary provision of all amino acids
is necessary for sustaining normal immuno-competence and protecting the bird
from a variety of diseases. In commercial diets, Lysine is limiting behind TSAA
Arginine ranges from third to fifth limiting depending on requirements and the
ingredients used.
Branched-Chain Amino Acids
Bhargava et al. (1971a) conducted
experiments measuring growth and antibody production to Newcastle disease virus
in chickens fed various levels of Valine in both studies, Valine need for
antibody production was higher than that of growth. In the subject of poultry
nutrition Konashi et al. (2000) evaluated dietary reduction (50% of the control
level) in the branched-chain amino acids and noted a reduction in the relative
size of the thymus and bursa. The specific branched-chain amino acid that is
most important for immune organ development (Valine, Isoleucine, or Leucine) in
the former study is unknown because the 3 were reduced in the diet
concomitantly.
Threonine
Threonine is an important limiting
amino acid in livestock and in  poultry
industry, which is often added to the feed as poultry feed supplement.
Threonine is usually the second limiting amino acid for pig and the third for
poultry. Like lysine, to which it acts as complementary, threonine is an
essential amino acid for body protein deposition and growth. Thus, deficiency
in threonine affects the utilization of lysine and consequently overall  animal nutrition status . Threonine is needed
in gastrointestinal mucin production, and thereby involved in immune response.
It has also been shown to improve livability of heat-stressed broilers (Lemme,
2001). Sanitary status, animals' environmental conditions and other factors of  animal nutrition impact the Threonine Lysine
requirement.
Tryptophan
In animal nutrition sector It is
essential amino acid & has emerged as a regulator of many immunological and
physiological processes. Its plasma concentration declines in suffering from
different illnesses and inflammations (induced or natural), suggesting an
increased utilization of the amino acid in such instances (Le Floc'h et al.,
2004). IBDV primarily impairs the humoral immune response which is followed by
sever immune-suppression due to down regulation of T cells and macrophages.
Conclusion
Feed accounts for 65-70% of the total costs in animal
nutrition industry . Any operation must therefore have clear targets to
optimize poultry feed supplement requirements and reduce poultry feed
supplement cost. The high density confinement rearing of birds with limited use
of antibiotics has made it essential to find a solution for enhancement of
immune response by poultry nutrition alteration. Not only does the immune
system benefit directly from proper poultry nutrition, but indirectly proper poultry
nutrition will also prepare the bird for periods of stress, reducing the
adverse effects of stress and enhancing recovery from stressful periods.