ANN 602- ROLE OF VITAMINS AS

IMMUNOMODULATORS

SUBMITTED TO, SUBMITTED BY,

DR. RAJESH NEHRA PREETHI.S
DEPT OF ANIMAL NUTRITION, M.V.Sc 1st Yr,
CVAS BIKANER, DEPT OF LIVESTOCK
RAJUVAS. PRODUCTION MANAGEMENT,
CVAS BIKANER.
 VITAMIN
• A vitamin is a substance that makes you ill if you
don’t eat it.” (Albert Szent-Gyorgyi, Nobel Prize in
Physiology or Medicine, 1937).

• VITAMIN : An organic compound, vital nutrient,

required in limited amounts.

• Thirteen vitamins are universally recognized at

present.
• Vitamins are classified according to their biological
and chemical activity. Vitamins have diverse
biochemical functions.

• Vitamin D, have hormone-like functions as

regulators of mineral metabolism.

• Vitamin E, C function as antioxidant.

• The largest number of vitamins B complex function

as enzyme cofactors.
 IMMUNITY
• Immunity refers to reactions by an animal’s body to foreign
substances such as microbes and various macromolecules,
independent of a physiological or pathological result of the
reaction (Abbas et al. 1991).

• In response to invasion of pathogens, the immune system

first executes innate and then acquire host defense systems
of high diversity.

• Nutritional status of host critically determines outcome of

the war against invading pathogens.
 Mechanisms by which diet influences
immunity
• Diets influence immunity through several mechanisms.
These include meeting the substrate needs of immune
system cells,
• Deprivation of nutrients from pathogen,
• Through direct regulatory effects on cells of immune
system, through changing the balance of hormones that
regulate immunity,
• Through reduction of collateral damage induced by an
immune response, and physical and chemical
immunomodulatory action of non-nutrient components of
feeds.
Meeting substrate needs of immune system
cells.
• Although immune system is relatively small, it is a vital system and
its requirements must be met.

• Substrates (energy, amino acids and all nutrients) are necessary for
the anabolic activity of immune system’s cells (leukocytes), such as
proliferation and antibody production.

• In young animals, a severe deficiency of any nutrient impairs

immunocompetence (Cook 1991).

• When leukocytes become activated, they express high levels of

nutrient transporters, which allow them to easily obtain necessary
nutrients even when they are at low concentrations.
• The immune system can also mobilize nutrients from muscle and
other tissues.

• When leukocytes become stimulated by pathogens, they release a

series of pro-inflammatory cytokines like interleukin 1, tumor
necrosis factor and interleukin 6 that go throughout the body and
redistribute nutrients, especially those from skeletal muscle.
IMPORTANT NUTRIENT IN IMMUNE
FUNCTION.
 IMMUNITY.. WHEN & WHY..??
• The immune system accounts for a relatively minor portion of
total nutritional requirements in the normal healthy animal
but activation of the immune system in response to an
immune challenge has a major impact on nutritional status
and requirements for most nutrients.

• Nutrient deficiencies increase susceptibility to most infectious

diseases, including bacterial, viral and parasitic diseases. Once
disease has developed, nutritional deficiencies increase the
severity of the disease and increase the probability of
secondary infections.
• Deficiencies of vitamins or trace minerals significantly
depress immune function and resistance to stress even
when animals are otherwise well fed with sufficient energy
and protein.

• Stress increases requirements of many nutrients essential

for immune function and leads to multiple short term
nutrient deficiencies.

• Some nutrients such as vitamin E can be fed at levels above

normal requirements to stimulate immunity of
immunosuppressed animals.
• Stressed cattle are often deficient in energy, amino acids,
vitamin A, B-vitamins, calcium, phosphorus, potassium,
magnesium, zinc, and copper.

• Antioxidant requirements are markedly increased by both

stress and disease, because both result in accelerated
productive of highly reactive oxygen by products,
peroxides, and free radicals.

• Antioxidants such as vitamin E and vitamin C are quickly

depleted in stressed animals, particularly in the white
blood cells where they are critically important for immune
function.
 Role of micronutrients in Immune
response.
• The group of antioxidant vitamins (carotenoids, vitamin E and
vitamin C) has recently received a great deal of attention
because of their action on immunity and disease etiology.

• It is well established now that antioxidants improve immunity

following stress.

• Free radicals are generated during metabolism, immune

response, synthesis of corticosteroid, auto-oxidation of
unsaturated organic molecules (e.g. polyunsaturated fatty acid
esters), radiation, or from activities of some oxidases,
dehydrogenases, and peroxidases.
• Tissue defence mechanisms against free-radical damage generally
includes vitamin C, vitamin E, and ß-carotene as the major
antioxidant sources.

• In addition, several metallo-enzymes which include glutathione

peroxidase (selenium), catalase (iron), and superoxide dismutase
(copper, zinc, and manganese) are also critical in protecting the
internal cellular constituents from oxidative damage.

• Vitamin E acts as antioxidant by quenching free radicals generated

during metabolism.

• α-Tocopherol was proposed to be the most important lipid-soluble

radical scavenging chain breaking antioxidant in membranes and
plasma.
• It functions by trapping peroxyl free radicals, especially at
ambient oxygen tension (Burton and Ingold 1984). Vitamin
E may guard against peroxidation of arachidonic acid
(Lawrence et al. 1985).

• Studies showed that supplementation of vitamin E

effectively increased antigen specific antibody responses in
various species of animals.

• Supplementation of chick diets with vitamin E resulted in

higher concentration of serum interferon.

• Vitamin E administration to calves enhanced immune

response and weight gain,
• Vitamin C or L ascorbic acid is the most important
antioxidant in extracellular fluids (Stocker and Frei 1991)
and can protect bio-membranes against lipid peroxidation
damage by eliminating peroxyl radicals. (Frei et al. 1989)

• Ascorbic acid is reported to have a stimulating effect on

phagocytic activity of leukocytes on function of the
reticulo-endothelial system, and on formation of
antibodies.

• Vitamin C can stimulate the production of interferons, the

proteins that protect cells against viral attack (Siegel 1974).
 VITAMIN D
• Vitamin D3 ,the most physiologically relevant form
of vitamin D, is synthesized in the skin from 7-
dehydrocholesterol.

• A process which depends on sunlight, specifically

ultraviolet B radiation (wavelengths of 270–300
nm).

• It is then converted in the liver to 25-

dihydroxyvitamin D3 (25(OH)D3), which is the main
circulating form of D3
• Finally, 25(OH)VD3 is metabolized in the kidneys to
1,25(OH)2VD3, the most physiologically active
VD3 metabolite
• In addition to being processed in the liver and the kidneys, VD3 can
also be metabolized by cells of the immune system.

• Cells of the immune system, including macrophages, dendritic cells

(DCs), T and B cells express the enzyme, and hydroxylate into
1,25(OH)2VD3.

• 1,25(OH)2VD3 acts on immune cells in an autocrine or paracrine

manner by binding to the vitamin D receptor (VDR)

• Finally, the enzyme 24-hydroxylase, which is most abundant in the

kidney and intestine, catabolizes 1,25(OH)2VD3 to its inactive
metabolite, calcitroic acid, which is then excreted in the bile.
 VITAMIN A
• Vitamin A is obtained from the diet either as all-trans-retinol,
retinyl esters or β-carotene.

• All-trans-retinol is esterified to retinyl esters and stored in the

liver, mostly in the stellate cells.

• In the tissues, all-trans-retinol and β-carotene are oxidized

to all-trans-retinal by alcohol dehydrogenases or short chain
dehydrogenase reductases, which are ubiquitously expressed
enzymes.

• All-trans-retinal is then oxidized to all-trans-retinoic acid

through an irreversible reaction catalysed by retinal
dehydrogenases (RALDHs),
• Vitamin A metabolites can also affect some aspects of the
adaptive immune response. Retinoic acid enhances
cytotoxicity and T-cell proliferation.

• Retinoic acid can inhibit B-cell proliferation, In addition,

retinoic acid inhibits B-cell apoptosis. These effects are
mediated through binding of vitamin A metabolites to RAR
receptors.

• A distinct set of vitamin A metabolites classified as retro-

retinoids can also affect general lymphocyte functions such
as B-cell proliferation and T-cell activation and proliferation.
THANK YOU