Transcript Part 1: Mechanisms and Management of Food Allergies

Food Allergies:
What’s New in Clinical, Community,
School and Food Service Applications
Janice M. Joneja, Ph.D., RD
2006
Food Allergy in the Past 5 Years
Nearly 4% of North Americans have food
allergies, many more than recorded in the
past
– Incidence of food allergy much higher in
children (>8%) than adults (<2%)
Prevalence of peanut allergy doubled in
American children younger than 5 years of
age in the past 5 years
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Food Allergy in the Past 5 Years
Incidence of food intolerances estimated to be
up to 50% of the population, but accurate
figures are not available because of the lack of
appropriate tests
– Incidence of food intolerances much higher in
adults than in children
Many food allergens have been characterized
at the molecular level, leading to increased
understanding of the causes of many allergic
disorders
3
Food Allergy & Food Intolerance
Food Allergy
Food Intolerance
• A generic term
describing an abnormal
• A response of the immune
system to an ingested
food or food additive
physiological response
to an ingested food or food
additive which is not a result
of a response of the
• Is not dose-dependent
immune system
• Is dose-dependent
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Management of Food Allergies and Intolerances
Management of food sensitivities consists of:
– Accurate identification of the food causing the
problem
– Educating clients on how to avoid relevant
allergens and intolerance triggers in foods
– Formulating appropriate diets to avoid the culprit
foods and replacing them with foods of equivalent
nutritional value
– Educating parents in measures to avoid
sensitization of their at-risk babies
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The Allergic Diathesis
Atopic dermatitis
(Eczema)
.
Gastrointestinal
symptoms
Sleep deprivation
Irritability
Mental fogginess
Fatigue
In infants:
failure to thrive
Asthma
(cough;
wheeze)
Food Allergy
Anaphylaxis
Allergic
rhinoconjunctivitis
(hay fever)
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Allergy is a Response of the Immune
System
Our immune systems are designed to
protect the body from invasion by foreign
materials
T cell lymphocytes detect foreign proteins
(antigens) in any form
T cells then trigger a series of
immunological reactions, mediated by
cytokines
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Antigen Recognition
 The first stage of an immune response is
recognition of a “foreign antigen” (protein or
glycoprotein)
 T cell lymphocytes are the “controllers” of the
immune response
 T helper cells (CD4+ subclass) (Th) identify the
foreign protein as a “potential threat”
8
Education of the Immune System
All foods contain proteins – derived from
plants and animals – all of which are
foreign to the human body
In order for food to be absorbed,
metabolized, and utilized by the body, the
immune system needs to be “educated”
that the foreign material is safe
This involves a complex series of
immunological reactions
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Immune System of the Digestive Tract
Immune system of the digestive tract is unique –
named the gut-associated lymphoid tissue
(GALT)
Recent evidence suggests that the most
important cells in the initiation of the recognition
process are the dendritic cells in the intestinal
mucosa
They take up dietary proteins and transport them
to the mesenteric lymph nodes (MLN)
Differentiation of the T cells takes place in the
MLN
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Oral Tolerance
In most cases this results in “education” of the T
cells to not respond to that food protein when it
enters via the oral route – called oral tolerance
Contrasts with the active immune responses
needed to protect the gut against continual
bombardment by invading pathogens and their
products (toxins, etc)
Also contrasts with the reduced responsiveness
to the millions of microorganisms that are
permanent residents of the large bowel
T cells involved in these processes are
designated Treg
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T cells involved in Oral Tolerance
T cell response depends on the type of T helper
cell that is activated
Latest research indicates that T cells that
produce a cytokine called TGF- are important
in inducing oral tolerance
– Sometimes called Th3 cells
T cells that produce IL-10 may also be involved
in tolerance
These also regulate immune response to
resident microflora, preventing the usual
immune inflammatory response to
microorganisms
___________________
Strobel and Mowat 2006
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T-helper Cell Subclasses
There are two subclasses of T-helper cells
Type 1: Th1
Type 2: Th2
Cytokines (the “control chemicals” of the immune
system) are released
Each subclass produces a different set of
cytokines
The types of cytokines generated determine the
resulting immune response
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Role of T-helper Cell Subtypes
Th1 triggers the protective response to a
pathogen such as a virus or bacterium
– IgM, IgG, IgA antibodies are produced
Th2 is responsible for the IgE-mediated
hypersensitivity reaction (allergy)
– IgE antibodies are produced
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Allergic Sensitization
Cytokines associated with Th1 (protective)
response are predominantly:
– INF-
– IL-2
Cytokines associated with allergic (Th2)
response are predominantly:
– IL-4
– IL-13
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Th1
Th2 Interactions
Factors promoting:
Th1
- Bacterial and viral infections
- Maturation of the immune system
Th2
- Parasite infestations
- Immature immune system
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Th1
Th2 Interactions
Factors promoting:
Th1
- Bacterial and viral infections
- Maturation of the immune system
- Antigen tolerance
Th2
- Parasite infestations
- Immature immune system
- Sensitization to antigen
Contributing factors:
- Genetic inheritance
- Early exposure to allergen
- Increased antigen uptake
-“leaky gut”
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Conditions That May Induce Th2
Response
Inherited allergic potential
Immaturity of the immune system
Inflammatory conditions in the gut that
interfere with the normal antigen
processing pathway
Immaturity of the digestive mucosa leading
to hyperpermeability (“leaky gut”)
Increased uptake of antigens
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Th1
Th2 Interactions
 Under certain circumstances (eg
eczema) Th2 cytokines suppress Th1
cell activity
 This causes a decrease in the level of
immune protection against
microorganisms
 As a result, infection by normally
harmless skin bacteria can occur
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Th1
Th2 Interactions
 In contrast, Th1 activity may suppress Th2
response
 Infection with some common childhood illnesses
may suppress allergy - the “hygiene theory”
 Certain microorganisms in the large bowel (the
resident microflora) can influence the Th1/Th2
balance – role for probiotics?
 Latest research indicates a possible role for a
new cytokine IL-18 in Th1/Th2 balance
____________________
Cebeci et al August 2006
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IgE-Mediated hypersensitivity
Intracellular Granules are Released
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Many Inflammatory Chemicals are Released
in the Allergic Reaction
Preformed:
– Histamine
– Enzymes
– Chemo-attractants
Newly formed
– Prostaglandins
– Leukotrienes
Each chemical has a different effect on tissues:
The allergic response is the combined effect of
them all
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Action of Inflammatory Mediators on Tissues:
 Histamine 
Vasodilation {blood vessels widen}
Swelling of tissues
Increased vascular permeability {blood vessels
become “leaky”}
–
–
–
–
–
angioedema (swelling)
rhinitis (stuffy nose)
rhinorrhea (runny nose)
urticaria (hives)
otitis media (earache)
Itching
Flushing
Reddening
Antidote: Antihistamines
Block receptors for histamine on reactive cells
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Priority Food Allergens In Canada
Peanuts
Tree nuts (almonds, Brazil nuts, cashews, hazelnuts
(filberts), macadamia nuts, pecans, pinenuts, pistachios,
walnuts)
Sesame seeds
Milk
Eggs
Fish
Shellfish (e.g. clams, mussels, oysters, scallops and
crustaceans (e.g. crab, crayfish, lobster, shrimp) )
Soy
Wheat
Sulphites
These Priority Allergens account for more than 95% of
severe adverse reactions related to food allergens
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Additional Factors Involved in Symptoms
of Food Sensitivity
Increased permeability of the digestive tract
(leaky gut)
– Inflammation:
Infection
Allergy
Autoimmune disease
Other diseases
– Immaturity (in infants)
– Alcohol consumption
Physical exertion:
Exercise-induced anaphylaxis
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Additional Factors Involved in
Symptoms of Food Sensitivity
Stress
Eating several different allergenic foods at the
same time
Other allergies occurring at the same time
(e.g. hay fever, asthma)
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Classification of Food Allergens
Class 1:
– Direct sensitization via the gastrointestinal tract
after ingestion
– Water-soluble proteins or glycoproteins
– Stable to heat, proteases, and acid
– Many are lipid transfer proteins
Class 2:
– Indirect sensitization by inhalation of air-borne
allergen
– Cross-reaction to foods containing structurally
identical proteins
– Heat labile
– Many are pathogenesis-related proteins
____________
Sampson 2003
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Oral Allergy Syndrome
(OAS)
OAS refers to clinical symptoms in the
mucosa of the mouth and throat that:
Result from direct contact with a food allergen
In an individual who also exhibits allergy to
inhaled allergens.
Usually pollens (pollinosis) are the primary
allergens
Pollens usually trigger rhinitis or asthma
Occurs most frequently in adults
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Oral Allergy Syndrome
Characteristics
Inhaled pollen allergens sensitize tissues of the
upper respiratory tract
Tissues of the respiratory tract are adjacent to oral
tissues, and the mucosa is continuous
Sensitization of one leads to sensitization of the
other
OAS symptoms are mild in contrast to primary
food allergens and occur only in and around the
mouth and in the throat
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Oral Allergy Syndrome
The foods cause symptoms in the oral cavity
and local tissues immediately on contact:
–
–
–
–
–
Swelling
Throat tightening
Tingling
Itching
“Blistering”
Foods most frequently associated with OAS
are mainly fruits, a few vegetables, and nuts
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Oral Allergy Syndrome
Allergens
Pollens and foods that cause OAS are usually
botanically unrelated
Occurs most frequently in persons allergic to birch
and alder pollens
Also occurs with allergy to:
– Ragweed pollen
– Mugwort pollen
– Grass pollens
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Oral Allergy Syndrome
Cross-reacting allergens
Birch pollens with:
–
–
–
–
–
–
–
–
–
–
–
–
–
Apple
Stone Fruits (Apricot, Peach, Nectarine, Plum, Cherry)
Kiwi Fruit
Orange
- Peanut
- Almond
Melon
- Hazelnut
- Walnut
Watermelon
- Carrot
- Anise
Potato
- Celery
- Caraway seed
Tomato
- Parsnip
Green pepper
- Parsley
Cumin
- Beans
Coriander
- Peas
Dill
- Lentils
Sunflower seed
- Soy
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Oral Allergy Syndrome
Cross-reacting allergens
Ragweed pollen with:
– Banana
– Cantaloupe
– Honeydew
– Watermelon
– Other Melons
– Zucchini (Courgette)
– Cucumber
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Expression of OAS Symptoms
Oral reactivity to the food significantly
decreases when food is cooked
Reactivity of the antigen depends on
ripeness
– Antigen becomes more potent as the plant
material ages
People differ in the foods which trigger
OAS, even when they are allergic to the
cross-reacting pollens
– Foods contain an antigen that is structurally
similar to the allergenic pollen, but not all
people will develop OAS to all foods having that
antigen
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Identification of Foods Responsible
for OAS Symptoms
Skin tests will identify the allergenic plant pollen
Skin testing has not been successful in
identifying persons who react to cross-reacting
food antigens
– Plant antigens are unstable and do not survive the
process of antigen preparation
– Crushing plant material leads to release of phenols
and degradative enzymes
Prick + prick technique are more reliable than
standard skin tests
– Lancet is inserted in raw fruit or vegetable, withdrawn
and then used to prick the person’s skin
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Latex-Fruit Syndrome
Allergy to latex often starts as:
Contact allergy to a latex protein, usually
through:
– Abraded (non-intact) skin
– Mucous membrane
– Exposed tissue (e.g. during surgery)
Inhalant allergy:
– Inhaled powder from latex gloves
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Latex Allergy
Cross-reacting allergens
As antigen comes into contact with
immune cells, repeated exposure leads to
IgE mediated allergy
Proteins in foods with the same structure
as proteins in latex trigger the same IgE
response when they are eaten
In extreme cases can cause anaphylactic
reaction
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Latex Allergy
Related foods
Examples of foods that have been shown to
contain proteins similar in structure to latex:
–
–
–
–
–
–
Banana
Citrus Fruits
Kiwi Fruit
Fig
Passion Fruit
Grapes
- Mango
- Melon
- Pineapple
- Papaya
- Peach
- Potato
-
Tomato
Celery
Avocado
Tree Nuts
Chestnut
Peanut
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Common allergens in unrelated plant
materials: Summary
OAS and latex allergy are examples of
conditions in which common antigens,
expressed in botanically unrelated plants,
are capable of eliciting a hypersensitivity
reaction
In practice, when a specific plant food
elicits an allergic response, foods in the
same botanic family rarely elicit allergy
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