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Immunity and nutrition
Int J Nutr Sci 2022;7(2):65-74
International Journal of Nutrition Sciences
Journal Home Page: ijns.sums.ac.ir
Review Article
Association between Nutrition and Immune System:
A Review
1,2 2* 1,3
Maryam Hamidianshirazi , Maryam Ekramzadeh , Amir Reza Hamidianshirazi , Ali
Zangene4
1. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
2. Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition, Shiraz University of Medical Sciences, Shiraz, Iran
3. Department of Veterinary Medicine, Beyza Branch, Islamic Azad University, Beyza, Iran
4. Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
ARTICLE INFO ABSTRACT
Keywords: Many human diseases are caused by infection with either viruses or
Immune system bacteria. The proper functioning of the immune system is essential for the
Infection survival of any individual throughout life. The optimal immune response
Nutrition depends on an adequate nutrition and appropriate food pattern to prevent
Micronutrient infection. For example, getting enough protein is important for optimal
*Corresponding author: antibody production. Minerals and vitamins are forms of nutrients (called
Maryam Ekramzadeh, PhD; micronutrients) that have the appropriate capacity to support the immune
Nutrition Research Center, system by providing preventive mediators of infectious diseases to reduce
Department of Clinical Nutrition,
School of Nutrition and Food the rate of destruction of cells transported by free radicals or to help the
Sciences, Shiraz University of better functioning of T-cells. Reduced intake of micronutrients such
Medical Sciences, Shiraz, Iran. as vitamins A, E, C, D, B6, B9, and B12, as well as minerals such as
Tel: +98-71-37251004
Email: mekramzade@gmail.com zinc, magnesium, iron, selenium, and copper can decrease resistance to
Received: February 1, 2022 infections. Therefore, it is necessary to design a review study that looks
Revised: May 2, 2022 at the role of micronutrients in preventing infectious diseases.
Accepted: May 10, 2022
Please cite this article as: Hamidianshirazi M, Ekramzadeh M, Hamidianshirazi AR, Zangene A. Association between
Nutrition and Immune System: A Review. Int J Nutr Sci. 2022;7(2):65-74. doi: 10.30476/IJNS.2022.94619.1180.
Introduction immune system (3). Also, vitamin D deficiency
Since birth, our bodies are encountered by increases the risk of respiratory infections. An
pathogens that live and replicate in an individual’s association has been observed between vitamin D
body. Not all microorganisms are detrimental, deficiency in the blood and increased susceptibility
for example, microbiota that have a symbiotic to acute respiratory infections (4). In 2017, Martino
association with our digestive system (1). However, conducted a systematic review and meta-analysis
many pathogens can grow and multiply in the host of (n=10933) participants and reviewed 25 clinical
body using certain mechanisms. These mechanisms trials. Vitamin D supplementation was associated
cause disease in human beings. The body’s defense with a 12% reduction in respiratory infections (5).
system includes biochemical and other barriers that A balanced diet containing a range of minerals
fight pathogenic microorganisms (2). Every step of and vitamins is essential for immune cells to function
the immune response is dependent on the existence optimally to prevent infection (6-11). So immune
of certain nutrients. For example, scurvy is caused cells need a good energy source, macronutrients,
by a lack of vitamin C. Therefore, this indicates and micronutrients to fill in the articulation and
the effect of nutrients on the functioning of the preserve the immune response. The role of a
Int J Nutr Sci June 2022;7(2) 65
Hamidianshirazi et al.
healthy diet in immune function has become widely (NK) cells. Interferons are antimicrobial agents that
recognized, and the influence of various nutritional inhibit the growth of pathogens. Selenium increases
components on explicit aspects of the immune the production of IFNγ (25). Iron, zinc, and vitamin
role has been extensively researched (12). Proper C are effective in its production (22). Neutrophils
nutrition modulates oxidative and inflammatory and NK cells produce antimicrobial peptides such as
stress processes (13). Dietary compounds with anti- cathelicidins. These peptides absorb and kill bacteria
inflammatory and antioxidant properties include (26).The active form of vitamin D is effective in the
omega-3 fatty acids (14), vitamin C (15) vitamin gene expression of these peptides (27).
A (16). and selenium (17). Also, probiotic bacteria NK cells kill pathogens via cytotoxins (2).
and bovine colostrum are effective in improving Vitamin A is effective in maintaining the function of
the functioning of Th1 and the immune system. NK cells and vitamins B6, B12, C, and E, and folate
Docosahexaenoic acid (DHA) and omega-3 are involved in their cytotoxic activity (2). Next,
fatty acids can reduce the damaging effects of neutrophils and macrophages migrate to infected
inflammation. Therefore, the purpose of designing areas. Neutrophils kill the infection and macrophages
this review study is to investigate the known clear the cellular waste (28). Macrophages need
mechanisms of micronutrients that are essential iron and vitamin D for their normal function (29).
for the functioning of the immune system and to Vitamin D also enhances the phagocytic activity of
determine the effects of an inadequate diet on the macrophages. Vitamin C facilitates the movement
risk of infection. of neutrophils (30).
Phagocytes digest microbes and reactive oxygen
Immunity species (ROS) is produced during this process.
Resistance to pathogens has been referred to as Finally, a combination of digestive enzymes,
immunity. Inflammation is a biological reaction of peptides, and oxidants causes phagocytes to die
the immune cells that can be caused by a diversity of and burst (12). Vitamins C and E have antioxidant
factors, including pathogens, tumors, and damaged properties and are effective for optimal oxidative
cells. The immune system consists of two parts of explosion performance (2). Selenium acts as a
acquired and innate (18, 19). regulator of cellular antioxidants (via glutathione
peroxidase) and is therefore effective for the function
Innate immune Response of leukocytes. Zinc also improves the function of
The innate immune system is the initial reaction phagocytes by modulating oxidative explosion
to infection. The innate immune system can be activity (31). On the other hand, zinc has antioxidants
characterised by three protection mechanisms that have a protective effect against ROS (32).
including (i) physical barriers; (i) cellular
components; and (iii) humoral responses. The innate Inflammatory Reaction
reaction is quick, but not specialised (3, 18, 20, 21). Cells can be damaged by pathogens. Raising
body temperature is an inflammatory response to
Physical Barriers in Innate Immune System eliminate any foreign matter. Fever can exacerbate
The first line of the immune system includes the the effects of IFNs and the body’s reactions to
surfaces of the body (mucus membranes and the tissue repair. Following cell damage, the capillaries
skin), which form chemical and physical barriers constrict and histamine is released from the mast
against pathogens. Micronutrients are involved cells, leading to dilation and increased capillary
in the proper functioning of this line of defence. permeability. Basophils and platelets migrate to the
For example, iron is essential for cell growth (22). infected site. Increased blood flow dilutes infections
Vitamin A and zinc are essential for maintaining and bacterial toxins. Prostaglandins, bradykinin,
the integrity of mucous and skin cells, and vitamin and leukotrienes also help capillaries increase the
C is essential for enhancing collagen synthesis (22). number of neutrophils to kill pathogens. Finally,
Intestinal microbiota compositions are affected by macrophages phagocytose dead cells (33). Vitamin
vitamins A, D, B9, B6 and B12 (23). Antioxidants A activates macrophages (12). Vitamin D increases
such as vitamins C and E are effective in protecting the expression of anti-inflammatory cytokines by
cell membranes against free radicals (24). macrophages through positive regulation of MAPK
phosphatase-1 and suppression of p38 activation
Cellular Components in Innate Immune System (34), and vitamin E modulates the production
Some pathogens cross the first line of defence, of prostaglandin E2 (which has inflammatory
but encounter the second line of defence, such as properties) (12) and vitamin C reduces histamine
phagocytes, interferons (IFNs), and Natural killer levels and cytokine production (35).
66 Int J Nutr Sci June 2022;7(2)
Immunity and nutrition
Acquired Immune Response the immune system (39). Step 2 involves the supply of
The obtained immunity is dependent on the glutamine, which is a common fuel for immune cells
ability of the immune cells to differentiate between and the body, especially during strenuous exercise.
their own cells and unwanted invaders. Pathogens This step plays a role in providing more nutrients than
that overcome initiate immune response biochemical the first stage in the performance and better response
mechanisms quickly, identify pathogens, and of the immune system against invading factors (39).
eliminate the risk through plentiful immune cells. The goal is to communicate with the immune system
The acquired immune response has the capability to in order to control how it works.
precisely recognize a pathogen and ‘remember’ it if Step 3 allows dynamic communication with
exposed to it again. Acquired immunity is the defence the body’s defense system to control its function
that we gain through life when we face with numerous to the desired goal. For example, probiotic bacteria
illnesses or defences against them for vaccination. and bovine colostrum are effective in improving
This immunity produces antibodies when it spots a functioning of Th1 and the immune system. Also,
microorganism in the body. Specific offensive agents docosahexaenoic acid )DHA) and omega-3 fatty acids
can initiate slower-acquired immune operations that that can reduce the damaging effects of inflammation
use B and T cells. They detect antigens present on the (39). Step 4 surveys the relationship between diet,
pathogens and produce antibodies against them; they environment, and genome; thus, a good diet can
can also neutralize or detect pathogens being attacked be effective in eliminating disease and improving
by other immune cells (20, 36). Acquired immunity quality of life (39).
takes 5 to 10 days to produce antibodies, and during
this time, innate immunity becomes aggressive to Effect of Micronutrients on Improving Body
preserve the levels of pathogens (18, 20, 21). Defense and Tracking the Incidence of Infection
There are three types of T cells. Cytotoxic CD8+ Optimal amounts of micronutrients are needed
T cells kill pathogens after identification of peptide for the body’s active defense system, and these
antigens on the pathogens membrane. CD4+ T helper amounts vary at each stage of a person’s life (2). It
(Th) cells support B and other T cells to accomplish is recognized that an apparent lack of micronutrients
their functions. Regulatory T cells (Tregs) prevent has a negative impact on the immune system and
excessive immune reactions (37). Th cells makes people more susceptible to infections (40), and
differentiate into Th1 and Th2 cells. Th1 cells secrete a lack of micronutrients is recognized to increase the
IL-2 and IFNγ in response to viruses and bacteria. risk of illness and humanity. Lack of micronutrients
Th2 cells also produce several other ILs (IL-4, IL- causes destructive effects on the health of the body
5, IL-10 and IL-13) against pathogens. Vitamin A is (34) (Table 1).
essential for the development and differentiation of
Th1 and Th2 cells (12). Vitamins E, B6, and B9, and The Effects of Nutrients on Infectious Disease
zinc are involved in improving Th1 function, while As discussed, minerals and vitamins play an
vitamin D inhibits its activity (12). Lymphocytes essential role in every stage of the immune system.
begin to multiply after exposure to antigens and their Lack of micronutrients is considered the most
detection. Vitamins C, E, B12, and B6 are involved in common cause of secondary immunodeficiency and
the differentiation and proliferation of lymphocytes, infection (71). Studies show that many people have
while calcitriol prevents the proliferation and an inadequate daily intake of micronutrients (72).
differentiation of lymphocytes (38). The acquisition
of mucosal-homing properties by lymphocytes is Vitamin A
facilitated by vitamin A (12). Vitamin A supplementation (50,000-200,000 IU
every 4–6 months) in offspring can decrease the
Effect of Nutrients on Immune System incidence of malaria (73), measles, and diarrhea
The immune system and nutrients interact in four (74). Serum levels of vitamin A were also low in
steps (39). Steps 1 and 2 do not play a role in providing patients with AIDS (75). However, other studies in
essential nutrients to the immune system, so these children did not find any relation between vitamin
two steps are called inactive. Steps 3 and 4 play a A consumption and a decrease in the incidence of
role in regulating the immune response, for example, pneumonia or lower respiratory tract infections
through gastrointestinal receptors, so these two steps (RTI) (76, 77).
are called “active methods” in increasing the immune
system. Step 1 includes nutrients such as protein, Vitamin D
vitamins (vitamins A, E, and C), and minerals (Fe Vitamin D deficiency is linked to infection
and Zn) that are provided to improve the function of diseases. This deficiency has also been observed in
Int J Nutr Sci June 2022;7(2) 67
Hamidianshirazi et al.
Table 1: The role of micronutrients on the body’s defence system.
Micronutrient The role of micronutrients Foods rich in micronutrients
Vitamin A Vitamin A is involved in the cell differentiation of Th1 In animal sources including liver, milk fat,
and Th2 cells (16). It is vital for supporting the gut poultry eggs, offal, liver, and turkey meat; in
barrier (23). It also has immunoregulatory activities by plant sources including carrots, spinach, orange
decreasing the toxic influence on ROS and modifiable juice, sweet potatoes, and cantaloupe (43, 44).
gap‐junctional communication and membrane fluidity
(41). It controls the amount and role of NK cells, IL‐2,
and IFNγ production (42) and their involvement in the
activity of macrophages (12).
Vitamin D Calcitriol controls the regulatory proteins of Liver fish, oil fish, butter, cream, egg yolk, liver,
microbiota, which protects the intestinal barrier (45); and shitake mushroom (44, 52).
it grows the protein of tight junction expression in
the gut (46). It also improves the defensive system
in the lungs and corneal epithelium (47). Calcitriol
adjusts antimicrobial protein expression, which puts
death to pathogens (48). It preserves renal epithelial
barrier role (49) and increases corneal epithelial barrier
role (50). Monocytes and macrophages have vitamin
D receptors; thus, this receptor increases conversion
induction from monocytes to macrophages (22). It
also plays a role in the movement of phagocytes (12),
prevents IFNγ production (51), and is involved in
reducing the expression of inflammatory factors by
macrophages (34).
Vitamin E It keeps cell membranes from the negative effects of Wheat germ oil, soy, safflower, corn, cottonseed,
free radicals (12), increases natural killer cell cytotoxic palm, canola, sunflower, raisins (44), and soaked
action (12), prevents the action of macrophages in the almonds (54).
production of PGE2 (24, 53), increases the production
of IL-2 (22), increases lymphocyte production, and
affects the function of T cells (22).
Vitamin C It protects cells against free radicals through collagen Fruits, vegetables, organ meats (44), citrus
synthesis. It preserves intracellular redox homeostasis fruits, red and green peppers, kiwi fruit,
(12). It reinforces the antioxidant function of Vitamin tomatoes, broccoli, brussels, strawberries,
E and glutathione (32). It modulates histamine and sprouts, and cantaloupe (54, 56).
cytokine levels (42). It increases NK cell actions
(12). It increases phagocytosis, ROS production, and
microbial killing (42). It also has a role in apoptosis
(42). It weakens extracellular trap (NET) construction,
therefore, decreasing related tissue hurt (55).
Vitamins B6 Vitamin B is involved in regulating intestinal Whole grains, vegetables, nuts, potatoes,
immunity. It promotes lymphocyte migration into chicken, bananas, meat, fish, eggs, and dairy
the intestine (57). It maintains or increases NK cell products (44).
cytotoxic activity (12). It promotes lymphocyte
proliferation; and it protects the Th1 immune response
(22).
Vitamin B9 Folate controls the action of T cells (57). It keeps or Liver, mushrooms, spinach, asparagus, broccoli,
increases NK cell cytotoxic activity (12). beef, potatoes, orange juice, and beans (57).
Vitamin B12 Beneficial microbes in the gastrointestinal tract use Beef liver, oysters, shellfish, liver, some fish
vitamin B12 to improve the body’s defenses (57). (herring, sardines, salmon, trout), and milk and
Vitamin B12 is involved in the function of T and NK milk products (44).
cells (22).
Iron Iron is important for the evolution of epithelial tissue Beans, spinach, liver, potatoes, beef, eggs,
(22) and the complicated control of cytokine function peanuts, chicken breast, and broccoli (56).
(22). It improves the M2 macrophage phenotype and
controls the inflammatory response of M1 (58).
68 Int J Nutr Sci June 2022;7(2)
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