DIET, IMMUNE AND INFECTION

References
1. Andrews JF and Griffiths RD, et al. Glutamine: essential for immune nutrition in the critical ill.
British Journal of Nutrition 2002; 87: p S3 S8.
2. Barbul A. Immunonutrition comes of age (Editorial). Crit Care Med 2000; 28:3: p 884 665.
3. Bistrian BR, Clinical aspects of essential fatty acids metabolism: Jonathan Rhoads lecture,
JPEN 2003; 27: 168 175.
4. Collin MD and Gibson GR. Probiotic, prebiotic, and synbiotics: approches for modulating the
microbial ecology of the gut. Am J Clin Nutr 1999; 69: 1052S 1057S
5. Fenton M and Silverman EC. Medical nutrition therapy for human immunodeficiency virus (HIV)
Disease in Krauses Food and Nutrition Terapy (Mahan, LK and Escott-Stump S eds), 2008: p
991 1020.
6. Gallagher ML. The nutrients and their metabolism. in Krauses Food and Nutrition Terapy
(Mahan, LK and Escott-Stump S eds), 2008: p 42 143.
7. Grimble GK and Westwood OM. Nucleotides as immunomodulator in clinical nutrition. Curr Opin
Clin Nutr Metab Care 2001; 4: 57-64
8. Heimburger DC. Nutritional support: general approch and complications in Handbook of Clinical
Nutrition (Heimburger DC and Ard JD, eds, 2006: p 262 281.
9. Luiking, YC et al. The role of arginine in infection and sepsis. JPEN 2005; 29: S70 S 74.
10. Maggini S, et al. Selected vitamins and trace elements support immune strengthening epithelial
barriers and cellular and humoral immune responses. British Journal of Nutrition 2007; 98: p
829 835.

Background
The role of nutrition in immune response

Nutrition has essential role to maintain immune-competence

Nutrition factor is required by all kinds of immune system, specific as

well as nonspecific

Disruption of a balance between intake and requirement of energy

and nutrients Malnutrition

immune-competence

immune-compromised

Genetic NUTRITION
Age
Fitness
Stress

Gender
Smoking

Etc

Etc

IMMUNITY
PHYSICAL BARRIERS:
SKIN MUCOSA, MUCOSA, MUCUS SECRETION
IMMUNE CELLS
ANTIBODIES

NUTRITION
CARBOHYDRATE

VITAMIN

PROTEIN

MACRO

MICRO

NUTRITION

NUTRITION
MINERAL

FAT
Genetic
Fitness

Age
Gender

Stress

Smoking

Etc

Etc

IMMUNITY
PHYSICAL BARRIERS: SKIN MUCOSA, MUCOSA, MUCUS SECRETION
IMMUNE CELLS
ANTIBODIES

NUTRITION
CARBOHYDRATE
PROTEIN

VITAMIN
MACRO

MICRO

NUTRIENT
STATUS
NUTRITION
NUTRITION
MINERAL

FAT

IMMUNITY
PHYSICAL BARRIERS: SKIN MUCOSA, MUCOSA, MUCUS SECRETION
IMMUNE CELLS
ANTIBODIES

Energy Balance & Immune Response (1)

EI
(foods)

EE
(Basal metab/Activity/infection)

1.
2.

Body Weight
Body composition

Immune system

ENERGY BALANCE AND IMMUNE

Actual BW < 60% Ideal BW immune competence
Obesity abnormalities of cellular & humoral
immunologic components

incidence of infection
Types of energy sources !

PROTEIN ENERGY MALNUTRITION

Marasmic & Kwashiorkor : A clinical manifestation of severe PEM
Disorder of immune system, including:
- Atrophy of lymphoid tissues
- lymphocyte concentrations
- response of cellular & humoral immunity
Disrupt integrity of epithelial cells invasion of microorganism

infection

acute phase response

activation of immune system

micronutrients loss

Morbidity & mortality

Effects of PEM: Firstly, studied in children

PEM Dysregulation of immune response

Immune response

Immune system needs:

Building substances
Energy sources

other physiological
processes

 food intake

NUTRIENT
STATUS:
MALNUTRITION

Malabsorption
Disorders of immune
function
Catabolism &
Utilization of
nutrients by the
body

IMMUNITY

Disorders of body barrier

that function as
Defense mechanism

INFECTION
Released nutrients
From the storage
For tissues synthesis &
growth
(Source: Brown, 2003)

Main immunologic deficits observed in PEM and pathogenic mechanisms

by which infection can increase nutritional deficiencies
(Sources: Chandra, 1980)

IMPAIRED IMMUNITY
- Cell-mediated immunity
- Mycrobicidal activity of phagocytes
- Complement system
- Secretory antibodies
- Antibody affinity

Undernutrition

Infection

Vomiting & malabsorption

Nutrient losses in urine & feces

Sequestration of nutrients
Increased catabolism
Diversion of nutrients

NUTRIENT
STATUS:
MALNUTRITION

IMMUNITY

INFECTION

NUTRITION THERAPY
General Nutrition
Energy Requirement and Composition
Vitamins
Minerals

Specific Nutrients Immunonutrients

Antioxidants: A, C, E, Carotenoids, Selenium, Zinc,
Copper
Glutamine, arginine, nucleotide
Probiotics

ENERGY REQUIREMENT FOR

MALNUTRITION PATIENTS
Indirect calorimetry
Equations Harris Benedict
BEE () = 66,47 + 13.75W + 5.00H 6.76A
BEE () = 655.10 + 9.56W + 1.85H 4.68A
Weight (W) = kg; Height (H) = cm; Age (a) = years

Energy goals in refeeding a hypometabolic starved patient:

Days

Energy Goal

12

BEE x 0.8

34

BEE x 1

46

BEE x 1.1 1.4

6+

BEE x 2

Excessively rapid feeding is risk, because of hypophosphatemia and heart failure.

Nutritional support should be initiated cautiously, to allow patient adaptation to new
energy and glucose load. Taking up to a week to reach to reach the final calorie goal.
Ref 8

RECOMMENDED NUTRIENT COMPOSITION

Protein
15%

Fat
Carbohydrate <30%
>55%

SFA <7% total calorie

PUFA <10% total calorie
MUFA < 15% total calorie

Cholesterol: <300 mg/d

Fiber: 20-30 g/d

Ref 6

The sites of micronutrients on the immune

system

Ref 10

IMMUNONUTRITION
= Immune enhanced nutrition
= Immune boosting nutrition
= Immune modulating nutrition
Definition
Nutrients or specific food items which ability to
modulation of immune system and the
consequences of activation of the immune system
Ref 2

IMMUNONUTRITION
The term given to describe special enteral /
parenteral feeds containing:

Antioxidants
Glutamine
Arginine
Omega-3 fatty acids
Nucleotides
Probiotics
Ref 2

The nature of critically ill patients

conditions
Malnutrition
Compromise of immune system
Infection

Length of ICU and hospital stay

Morbidity
Mortality
Costs of care
Ref 2

THE AIM OF IMMUNONUTRITION

to preserve or enhance the immune
response in critically ill patients
to improve outcome and reduce the
length of stay required in hospital

Ref 2

VITAMIN A
Vitamin A is antioxidant
Vitamin A regulates of:
innate and cell mediated immunity
Humoral antibody response

Vitamin A deficiency:
The integrity of mucosal epithelium is altered susceptibility to
pathogens in eye, respiratory, GIT
Diminished phagocytic and oxidative burst activity of macrophages
activated during inflammation
A reduced number and activity of NK cells
The increased production of IL-12 and pro-inflammatory TNF

Ref 10

VITAMIN A
Vitamin A supplementation:
morbidity and mortality from acute measles in infants and
children, diarrhoea disease in pre-school children in developing
countries, acute respiratory infection, malaria, TBC etc
Increased delayed type hypersensitivity (DTH) in infants which
may reflect of up-regulation of lymphocyte function
Improve antibody to various vaccines

Ref 10

VITAMIN C
Vitamin C is antioxidant
Vitamin C is highly concentrated in leukocytes and is used rapidly
during infection
Vitamin C enhance neutrophil chemotaxis.
Vitamin C stimulate the immune system by enhanching T lymphocyte
proliferation in response to infection increasing cytokine production
and synthesis of immunoglobulins
Vitamin C improve several components immune response such as
anti-microbicidal and NK cell activities, lymphocyte proliferation,
chemotaxis, and DTH response.
Vitamin C effective in ameliorate symptoms of upper respiratory tract
infection.

Ref 10

VITAMIN D
Most cells of the immune system (monocyte, macrophages and
thymus tissue) except B cells express of significant quantities of
vitamin D receptors
Vitamin D status influences the occurrence of Th1-mediated
autoimmunity disease which is in accordance with the ability of
1,25(OH)2D3 to inhibit maturation of dendritic cells and down regulate
production of the immunostimulatory IL-12, and the observed
increase in immunosuppresive IL-10

Ref 10

VITAMIN E
Vitamin E is a potent antioxidant
Vitamin E is strong lipid soluble antioxidant which is able to enhance
the immune response from free radicals and lipid peroxidation.
Vitamin E increases lymphocyte proliferation in response to mitogens,
production of IL-2, NK cell cytotoxic activity, and phagocytic activity
by alveolar macrophages, and causes an increased resistance
against infectious agents.
Vitamin E has potential effect to improve the overall immune
response, especially in the elderly.
Ref 10

FOLATE
Folate status may affect the immune system by inhibiting the capacity
of CD8+ T lymphocytes cells to proliferate in response to mitogen
activation
Folate deficiency enhances carcionogenesis causes of increased
damage to DNA and altered methylation capacity.
Folate supplementation of elderly improves overall immune function
by increase in NK cell activity, providing protection against infections.

Ref 10

VITAMIN B12
B12 deficiency with impairments in thymidine and purine
synthesis and subsequently in DNA and RNA synthesis,
leading to alterations in immunoglobulin secretion.
B12 deficiency showed abnormally in CD4+/CD8+ ratio and
suppressed NK cell effects.
Immunocompetent elderly with low vitamin B12 serum
concentration, had an impaired antibody response to
pneumococcal polysacharide vaccine
Ref 10

SELENIUM
Selenium is essential for optimum immune response and influences
the innate and acquired immune systems
Selenium is an antioxidant, playing a key role in the redox regulation
function through glutathione peroxidases that remove excess of free
radicals.
The selenoenzyme thioredoxin reductase affects the redox
regulation of several enzymes, transcription factors and receptors.
Selenium deficiency decreases immunoglobulin titres and spects of
cell-mediated immunity.

Ref 10

ZINC
Zinc is essential for highly proliferating cells, especially in the immune
system and influences both innate and acquired immune functions.
Zinc is involved in the cytosolic defence as an antioxidant.
Zinc is an essential co factor for thymulin which modulates cytokine
release and induces proliferation.
Zinc supports a TH1 response.
Zinc maintains skin and mucosal membrane integrity.
Zinc increases cellular components of innate immunity, antibody
responses and the number of cytotoxic CD8+ T cells

Ref 10

COPPER
Copper status alters several aspects of neutrophils,
monocytes and superoxide dismutase.
Working together with catalase and glutathione
peroxidase in the cytosolic antioxidant defence
against ROS.

Ref 10

IRON
Iron is essential for electron transfer reactions, gene
regulation, binding and transport of oxygen, and regulation
of cell differentiation and cell growth.
Iron is involved in the regulation of cytokine production and
in the activation of protein kinase C
Iron is necessary for myeloperoxidase activity which is
involved in the killing process of bacteria by neutrophils
through the formation of highly toxic hydroxyl radicals.
Ref 10

IRON
Pathogens such as infectious microorganisms and
viruses require iron and other micronutrients for
replication and survival as well, it seems essential
to restrict of the infecting microorganism to iron, but
to maintain a suitable concentration of iron that the
host can mount an optimum immune response and
avoid the possibility of excess amounts of iron
which may induce free radical mediated damage.
Ref 10

PROBIOTICS

LIVE microbial which when administered

in adequate amounts confer a health
benefit on the host
FAO / WHO 2001

Gut: the largest immune

defense
tonsils

thymus

lymph nodus

spleen
intestinal
lymphatic tissue
(Peyer-Plaques)
appendix
inquinal lymph nodes
bone marrow

Skin

Respiratory tract:

2.5 m2
80

m2

Gut

400 m2

Urinary tract

5 m2

CRITERIA OF PROBIOTIC
Apathogen / non toxic
Contain a large number of
viable cells
Remain viable during
storage and use

Be capable of surviving and

metabolizing in the gut

Exert a beneficial effect on

the host

Most probiotic strains are

commensal micro-organisms
without pathogenic activity

GUT BARRIER DEFENSE MECHANISM

Exclusion of the antigen

Elimination of the foreign antigen that have penetrated the
mucosa
Regulating antigen specific immune response
Ref 4

PROBIOTICS HEALTH BENEFIT

Immunomodulatory effect

phagocytosis
production of IgA
release of cytokines: TNF, IL-6 and IL-10
human immune defense
manifested of atopic eczeme in children

Elimination of lactose intolerance

Anti-diarrhea
Suppressed Helicobacter pylori
Prevention of cancer
Hypocholesterolemic
Antioxidant

Ref 4

GLUTAMINE
Most abundant free amino acid in:
plasma ( 20% of the total circulating free amino acid pool)
skeletal muscle ( 60% of the total circulating free amino acid pool)

Primarily synthesized in the skeletal muscle

Substrate for gluconeogenesis and ureagenesis
Precursor for nucleotide and glutathione
Oxidative fuel high cell proliferation rate in mucosa small intestine as
enterocyte, colonocyte and immune cells
Non essential in normal conditions
Conditionally essential during catabolic state
Ref 1

EFFECT OF GLUTAMINE ON IMMUNE FUNCTIONS

Lymphocytes

Macrophage

PMNs

Ref 1

ARGININE

Conditionally essential during catabolic state

Wound healing (synthesis of collagen, GH)
Upgrades immune function
Maintain the bodys nitrogen balance
Precursor of Nitric Oxide, Glutamine
Hormone Secretion Activity,
Growth Hormone, Insulin, Glucagon

Ref 9

EFFECT OF ARGININE ON IMMUNE FUNCTIONS

Stimulate the response of monocyte to antigen
Reduce the destructions of lymphocyte & T-helper
Modulate functions of cell lymphocytes, macrophages, and
neutrophils

Ref 9

OMEGA 3 FATTY ACIDS

EFFECT OF 3 IMMUNE FUNCTION

immune function
Booster neutrophil activity
Distribution of lymphocyte throughout the body
Reducing the bodys inflammatory response to
trauma ( level of CRP, IL-6, leukotriene B4, PAF)

Ref 3

NUCLEOTIDE
EFFECT OF NUCLEOTIDE ON IMMUNE FUNCTION
maintaining cellular integrity and function
stimulate natural killer cell activity againts tumour
cells and virus infected cells
enhance the production of repair cells known as
enterocytes, and also to prevent the loss of important
bacteria in the gut

Ref 7

Bacteria

IMMUNO
COMPROMIZE

HIV INFECTION

Fungi

OPPORTUNISTIC
INFECTION

Protozoa
Virus

Problems in :
Ingestion
absorption
Digestion
Metabolism

MALNUTRITION

use of nutrients

Diarrhea, vomiting
Malabsorption
Fever
Weight loss
Wasting
Etc

Ref 5

Nutrition Management in HIV

Problems in :

General Nutrition
Adequate energy requirement and composition
Micronutrients
Fluids

Specific Nutrition
Antioxidants
Probiotics
Immunonutrition

Route: oral, enteral, parenteral

Delivery: small frequent, nutrient-dense meals

Appetite stimulants, anabolic therapies

ingestion
absorption
Digestion
Metabolism
use of nutrients
Diarrhea, vomiting
Malabsorption
Fever
Weight loss
Wasting
Etc
Ref 5

Regular exercise and physical activity