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
2
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
4
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
induce tolerance of foods
5
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)
6
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
7
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
9
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
10
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)
11
Oral Tolerance
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
12
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
___________________
Strobel and Mowat 2006
13
T cells involved in Oral Tolerance
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
14
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
15
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
16
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
17
Immunological Pathways to Protection, Allergy, or Oral Tolerance
Antigenpresenting cell
T helper ( CD4+) cells respond
Receptor
Antigen
Th0
MHC
Class II
IL-2
IL-3
IL-4
IL-5
Il-13
INF
GM-CSF
White blood cells aid
the immune system in
recognizing foreign
proteins
Th1
Viruses
and
Bacteria
Il-2
Il-3
IFN
GM-CSF
IgG
Specific cytokines determine
which response takes place:
Th1 = protection
Th2 = allergy
Allergens
Th2
Il-3
T helper cells produce
Il-4
Il-5
characteristic cytokines
Il-13
GM-CSF
Transport to thymus
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
IgE
CD4+CD25+Treg
IL-10
TGF-β1
Th3
Oral Tolerance
Tr1
Anergy:
No immune response18
Th1
Th2 Interactions
Factors promoting:
Th1
- Bacterial and viral infections
- Maturation of the immune system
Th2
- Parasite infestations
- Immature immune system
19
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”
20
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
21
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
22
IgE-Mediated Allergy
Intracellular Granules are Released
23
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
24
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
25
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
26
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
27
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)
28
Classification of Food Allergens
Class 1:
– Direct sensitization via the gastrointestinal
tract after ingestion
– Water-soluble proteins or glycoproteins
– Stable to:
Heat (cooking)
Proteases (digestive enzymes)
Acid (gastric acid)
– Many are lipid transfer proteins
____________
Sampson 2003
29
Classification of Food Allergens
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
produced when a plant is under stress
30
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
31
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
32
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
33
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
34
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
35
Oral Allergy Syndrome
Cross-reacting allergens
Ragweed pollen with:
– Banana
– Cantaloupe
– Honeydew
– Watermelon
– Other Melons
– Zucchini (Courgette)
– Cucumber
36
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
same 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
37
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
38
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
39
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
40
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
41
Common allergens in unrelated plant
materials
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
42
Legume Allergy
There is no evidence to support the
thinking that peanut-allergic
individuals should avoid all legumes
Avoidance of legumes such as soy, chick
peas, lentils, beans, peas, licorice, carob,
and all other members of the
Leguminoceae family, to which peanut
belongs, is only necessary when allergy to
the individual foods has been identified
_________________________
Bernhisel-Broadbent et al 1989
43
Legume Allergy
In laboratory experiments, crossreactivity between peanut and soy is
quite frequent, but in clinical trials, the
cross-reactivity is quite uncommon
– One study reports only 2 out of 41 peanutallergic patients reacted mildly to other
members of the legume family
44
Peanut and Soy Allergy
Increase in the incidence of soy allergy,
especially in children
Soy and peanuts contain a similar
allergen
May be the result of exposure to the
allergenic protein, in the form of soybased infant formulas, in early infancy
when the child is at highest risk for
allergic sensitization
____________
Lack et al 2003
45
Peanut and Soy Allergy
Exposure to the soy allergen in infant
formula could prime the child’s
immune system to respond to the
peanut allergen, even when he or she
shows no signs of allergy to soy
As a result, the child could exhibit
allergic symptoms on an apparent
first exposure to the peanut
46
Tree Nut Allergy
Tree nuts are botanically unrelated to
peanuts
It is not necessary to avoid tree nuts
such as hazelnuts (filberts), Brazil
nuts, walnuts, pecans, almonds,
macadamia nuts, pine nuts,
pistachios, etc. unless the individual
has an allergy to them
47
Tree Nut Allergy
Nuts in a nut mixture are very difficult to
distinguish from each other
Risk of tree nuts, especially nut mixtures,
to contain, or to be contaminated by
peanuts
A person who has demonstrated allergy to
peanuts is usually advised to avoid nuts of
all types in the interests of safety
48
Take-Home Message
There are many different processes
involved in the expression of food allergy
No single lab test will identify the foods
responsible for symptoms
The presence of allergen-specific IgE does
not predict the response when the food is
eaten
Elimination and challenge is the only way
to identify the foods responsible for
symptoms
49
Take-Home Message
When the culprit food(s) have been identified
avoidance of the food is essential
Discourage unnecessary food restrictions
Client must be provided with:
– Information about which foods must be avoided
– Resources to recognize allergen in manufactured and
prepared foods
– Meal plans to supply complete balanced nutrition from
alternate sources
50
Take-Home Message
New research indicates that only the foods
causing symptoms should be avoided
When there are no longer any clinical
signs of allergy (symptoms) after
consumption of the food, tolerance has
occurred
In order to maintain tolerance the food
should be eaten regularly
51
Take-Home Message
The more foods that are tolerated, the
more foods will be tolerated – bystander
effect of TGF-
Unnecessary and prolonged avoidance of
a food may result in sensitization when the
food is eaten
52