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Immune nutrition
The importance of nutrition in
immunity
Anno 18 - No. 2
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March/April 2007
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CHRISTINE GAERTNER
Cognis Deutschland GmbH & Co KG, Nutrition & Health
Rheinpromenade 1,
Monheim, D-40789, Germany
COMPONENTS OF THE IMMUNE SYSTEM
The human immune system has developed over millions of
years into what it is today: a highly efficient and complex
system for defending the body against foreign infectious
agents, such as bacteria, viruses and parasites, as well as
malignant cells and other noxious agents.
Physical barriers form the body's first line of defense, including
the skin and mucous membranes in the airways and digestive
tract. Innate ("non-specific") and adaptive ("specific" or
"acquired") mechanisms together form the actual immune
system. Unlike other organs, such as the liver or adipose
tissue, the immune system extends throughout the body and
comprises a network of highly specialized immune cells and
small molecules.
The immune cells are organized into lymphoid organs (spleen,
lymph nodes - see Figure 1). They also circulate in the lymph
and in the bloodstream, and are dispersed at various sites in
the body such as the skin. A more detailed description of the
various immune cells follows later in this article.
The above mentioned "small molecules" include antibodies
and cytokines. Produced by specialized immune cells (Blymphocytes), antibodies react with antigens (any substance
triggering an immune response) to prepare the antigen for
destruction. Cytokines are small soluble molecules, mainly
peptides, which act as messengers between immune cells,
as well as between immune cells and cells of other organs
such as the liver, adipose tissue or the brain. Therefore,
cytokines are essential for integrating and coordinating the
immune responses. They include Tumor Necrosis Factor
alpha (TNF-α), Interferon gamma (INF-γ), Interleukins (IL-1,
IL-2, IL-6), and many more. The immune system is thus a
highly complex and interrelated system, so that efficient
communication between all elements is of key importance to
ensure coordinated action. Table 1 summarizes its various
components.
ABSTRACT
The human immune system is highly sophisticated, designed to ensure
that it can protect the body against invasive foreign or dangerous
substances. It can also be considered as the body's largest organ and,
as such, has substantial energy and nutrient requirements. The link
between nutrition and immunity has been established for many years
and, in 1968, the WHO recognised that there is actually a synergism
between infection and nutrition deficits (1). Since then, there has been
an "explosion" of knowledge about interrelations between nutrition and
immunity. This has confirmed the importance of optimal nutrition to
support optimal immune status. The present paper gives a brief
introduction into the human immune system, discusses factors which
influence immune status, including nutrition, and finally reviews the
evidence for immune modulating effects of selected nutrients.
Figure 1
Table 1. Elements of the immune system
CELLS OF THE IMMUNE SYSTEM
All immune cells originate from bone marrow and are
collectively named leukocytes, i.e., white blood cells. They
develop from their bone marrow stem cell precursors and
acquire their specific function in a multi-step process
involving various lymphoid and other organs.
The leukocytes can be broadly divided into two categories:
phagocytes, which ingest and digest invading microorganisms and account for 70-80 percent of total leukocytes
in the blood; and lymphocytes, which allow the body to
remember and recognize previous invaders, and which
account for the remaining 20-30 percent.
Phagocytes include granulocytes, monocytes and
macrophages. Monocytes circulate in blood and are both
precursors of macrophages as well as having phagocytotic
activity themselves. Monocytes migrate continuously from
blood into tissues, where they differentiate into
macrophages. Part of the first line of defense, macrophages
KEEPING THE IMMUNE SYSTEM IN BALANCE
Vitamin E
Vitamin E is the most important fat-soluble antioxidant
present in human and animal tissues, thus protecting lipids
in biomembranes from oxidative damage. In addition to its
antioxidative effects, it is involved in the modulation of
cellular signalling: it inhibits protein kinase C (PKC) (14), a
Anno 18 - No. 2
Following is a brief look at the immune effects of selected
individual nutrients known for their immune-modulating
effects. The selection is not intended to be complete and
certain nutrients established for their "immune-boosting"
effects, such as vitamin C, zinc, selenium, as well as proand prebiotics are not covered. However, excellent recent
reviews covering these nutrients are available (9-13).
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IMMUNE EFFECTS OF INDIVIDUAL NUTRIENTS
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March/April 2007
Although different types of pathogenic micro-organisms are
attacked and destroyed in slightly different ways, in general
immune responses to invading micro-organisms follow a
common pattern. If the pathogenic micro-organism has
Since the human immune system can be thought of as the
body's largest organ, it follows that its energy and nutrient
requirements are considerable. It needs:
- Glucose and glutamine for energy;
- Amino acids for synthesis of cytokines, antibodies, as well
as cell division and growth;
- Fatty acids for energy, synthesis of eicosanoids, as well
as cell membrane fluidity and thus functionality of
receptors;
- Vitamins as co-factors of enzymes, antioxidants, and for
cell differentiation;
- Minerals and trace elements as co-factors of enzymes.
These nutrient requirements increase still further when the
immune system is activated - in response to an infection, for
example. Energy and protein are both needed for the
synthesis of cytokines, antibodies, enzymes and others, as
well as for the proliferation of immune cells, especially of Tand B-lymphocytes. Fever increases the body's energy
needs (i.e. the basal metabolic rate) by as much as 13
percent for each 1°C, but even infections without fever
provoke a consuming, decomposing reaction termed
"catabolic response" (6). This relationship between
nutritional status and infection can create a vicious circle:
during infections, nutritional needs increase, but at the same
time, appetite and nutrient absorption decrease. As the body
draws on its resources, the likely result is a deficit in
nutrients, thus further promoting susceptibility to infections.
While nutrition deficits impair immune responses and thus
increase the risk of infection, the same is also true for "overnutrition": incidence and severity of specific types of
infections are higher in the obese, and lower antibody
responses to antigens have been reported in overweight
subjects (7, 8).
Thus, optimal nutritional status supports an efficient immune
response. This paper can only be intended as a very brief
introduction into the highly complex human immune system
and its relation with nutrition, a topic which is addressed in
many excellent text books and monographs.
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FIGHTING INFECTION
NUTRITION, IMMUNITY AND INFECTION
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The human immune system is an extremely powerful tool, a
fact which becomes especially apparent when it is thrown off
balance: both failure - as in immunodeficiency states - and
over-stimulation of the immune system - as in allergies - can
be devastating. The same applies when the regulatory
mechanisms controlling the distinction between "self" and
"non-self" get out of control, so that the immune responses
target the body's own tissues and cells, as in autoimmune
diseases or chronic inflammatory conditions. The status or
balance of an individual's immune system is determined by
many factors including genetic and exogenous influences
such as:
Nutrition: the most important exogenous factor influencing
the immune system, discussed in more detail below;
Age: the immune system changes throughout life. While the
immune system was previously believed to decline with age,
it is accepted today that only some aspects decline, while
others increase. This results in a progressive dysregulation
of the immune system with decreased cell-mediated
immunity and less appropriate antibody responses. These
changes are particularly apparent in elderly people with
suboptimal nutritional status and any type of disease (3).
Further, age-related changes in the innate immune cells of
the brain have implications both for the development of
neurological diseases such as Alzheimer´s disease, as well
as for the cognitive and behavioral impairments during
infections, which are more pronounced in the Elderly (4).
Stress: stress hormones such as glucocorticoids and
catecholamines are potent modulators of immune function,
and study results demonstrate an increased risk of infection
with psychological stress (5).
managed to cross the first line of defense - skin and mucous
membranes - and has actually entered the human body, the
innate immune system will respond and remove the
pathogen. Most of the micro organisms to which we are
exposed in daily life will be dealt with in this way. If exposure
to the pathogen continues or the pathogen continues to
multiply, overwhelming the innate responses, a more
powerful response from the adaptive immune system is
called to action in order to overcome the infection.
Immune nutrition
and other phagocytes initiate inflammatory responses by
secreting cytokines, and they recruit further immune cells to
the site of infection. Further, so-called dendritic cells have
phagocytotic activity, but their role is not to destroy
pathogens. Rather, they function as antigen-presenting
cells, displaying elements of ingested antigens on their
surface. They are involved in innate immune responses - by
producing cytokines and mobilizing lymphocytes such as
natural killer cells (NK-cells) - but also help to induce
adaptive immune responses, especially T-cell mediated
immunity (2). Lymphocytes can similarly be divided into
three main sub-types: T-Lymphocytes, B-Lymphocytes and
NK-cells.
T-Lymphocytes are responsible for cell-mediated adaptive
immunity and recognize antigens via receptors on their cells'
surface. There are three types of T-lymphocytes (or "Tcells"): T-helper, T-suppressor and cytotoxic T-cells.
B-Lymphocytes are responsible for humoral adaptive
immunity. They produce antibodies (Immunoglobulins, Ig's)
upon stimulation, or become memory cells. There are five
different classes of antibodies (IgA, IgD, IgE, IgG, and IgM),
each of which has its own function. Natural killer cells (NKcells) belong to the innate immune system and destroy
virus-infected or malignant cells directly and in a nonspecific way. Thus, natural killer cells are often the body's
first line of defense against viral infections.
Immune nutrition
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key player in the signalling of growth factors, cytokines and
hormones. Many animal and human studies suggest that
supplementation with doses higher than the RDAs (100 IU/d
and above) has beneficial effects on immunity, especially in
the elderly (15).
In humans, vitamin E has been shown to improve cellmediated immunity, as assessed by delayed type
hypersensitivity (DTH) responses and lymphocyte
proliferation (16-19). These effects are mediated by
increasing production of the "T-cell growth factor" Interleukin
2 (IL-2), and by reducing the production of T-cell
suppressive factor prostaglandin E2 (PGE2), the latter
increasing with age. Further, vitamin E supplementation
increased antibody titers upon vaccination (17), and reduced
the risk of acquiring respiratory infections or common colds
at doses of at least 200 IU (20).
Beneficial effects were not observed in all studies conducted
to date. However, in those studies showing no effect, lower
doses of vitamin E were used (21-23). Lack of observed
effects may also be due to the study design and
methodology (24, 25), and/or effects might not have been
expected in the specific study population (21-23, 26). The
findings in humans are supported by a wealth of data from
animal studies, as reviewed by Meydani et al. (15).
Beta-carotene
Beta-carotene is probably the best known member of the
large family of carotenoids, which are yellow to red lipophilic
plant pigments. In the human body, beta-carotene acts both
as an antioxidant and as a precursor to vitamin A. Vitamin A
has long been recognized for its importance in maintaining
immune responses: in vitamin A deficiency, susceptibility to
and mortality from infections are increased. However, later
research established that beta-carotene itself also acts as
an immune-modulating agent (27).
Higher beta-carotene plasma levels have been correlated
with a lower risk of infection (28). Beta-carotene generally
seems to support innate immunity, especially NK-cell
activity, rather than adaptive immunity: in humans, higher
intakes of beta-carotene via foods or supplements increased
the number of NK-cells and/or NK-cell activity (29-34). Low
NK-cell activity is associated with increased cancer risk and
increased mortality in the elderly (35, 36).
To improve NK-cell activity, sufficiently high doses, duration
of supplementation and beta-carotene status at baseline are
all important determinants of efficacy.
Further, beta-carotene supplementation has been
demonstrated to prevent immuno-suppression induced by
UV-light exposure (37-39).
CLA
Conjugated linoleic acid (CLA) refers to a class of
conjugated isomers of linoleic acid. The form typically used
in research and commercial products is a 50:50 mixture of
two isomers known to be biologically active: the cis-9, trans11 isomer (c9, t11), which is also the predominant form in
the diet; and the trans-10, cis-12 isomer (t10, c12).
The beneficial health effects of CLA only became known in
the early 1980s (40) - relatively recently compared to other
nutrients. While most data currently available on its immune
effects are therefore based on research in animals, human
intervention studies have demonstrated that CLA may
increase antibody titers upon vaccination (results
approaching statistical significance) (41), and increase
levels of IgA and IgM (42), which are instrumental in
activating further components of the immune system and
protecting mucosal barriers against infectious invaders. In
addition, CLA reduced common cold symptoms, specifically
cough and sore throat (43).
There is a multitude of data from animal studies
supporting these observations in humans (40). Other
human trials did not observe immune-stimulating effects,
most probably because of the forms of CLA and/or the
doses applied (44-46).
CONCLUSIONS
The relation between nutrition and immunity is complex. It is
established that nutrient deficiencies impair immune
responses. For some nutrients such as vitamin E, C or zinc,
intakes higher than the current RDAs have been shown to
"boost" immunity resulting in lower risk of infections and/or
symptom severity.
However, this may not be true for other nutrients, so that the
effects of each nutrient need to be considered individually.
Overall, improving immunity by optimizing nutritional status
may considerably improve the health status and thus have
significant benefits, both for an individual as well as from a
public health perspective.
REFERENCES AND NOTES
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