1. Food Allergies

2. Outlines What is food allergy Immunology concepts
What foods causes allergies
Possible ways to deal with food allergy
Resources for food allergies

3. Allergy is a specific immunological reaction to a normally harmless substance
An allergic reaction produces inflammation, a basic response of the body to injury

4. The symptoms of allergies to airborne substances include:
Sneezing, often accompanied by a runny or clogged nose
Coughing
Itching eyes, nose and throat
Allergic shiners (dark circles under the eyes caused by increase blood flow near the sinuses)
Watering eyes
Conjunctivitis (an inflammation of the membrane that lines the eyelids, causing red-rimmed, swollen eyes and crusting of the eyelids)

5. Allergies in developed countries are becoming more common.
In the U.S., food allergies afflict 2-2.5% adults and 6-8% children.
people in the U.S. die each year.
Death generally result from anaphylactic shock, often to peanuts or tree nuts.
More than 160 foods have been associated with allergic reactions.

6. Foods triggering anaphylaxis in Singaporean children (1992 – 1996)
124 children with acute anaphylaxis at NUH
mean age (yrs)
1. Egg and milk 11 % 0.7
2. Bird’s nest 27 % 4.5
3. Chinese herbs 7 % 5.0
4. Crustacean seafood 24 %
5. Others * 30 % 7.0
* Chicken, duck, ham, fruits (banana, rambutan), cereals, gelatin and spices
Goh et al. Allergy 54, 1999,

8. What is food allergy?
Food allergy is an inappropriate immune response to an otherwise harmless food.
Food allergy involves several types of immunological responses.
Food allergens are usually proteins.
Some foods may contain haptens or haptens carrier (A hapten- a small molecule that has the ability to combine with an Ab or a cell-surface receptor)

9. Types of food allergies
Immediate hypersensitivity with IgE which occurs within minutes to a few hours after ingestion of offending foods.
Systemic: Itching, Vomiting, Abdominal cramps, diarrhea and respiratory distress, and in severe cases anaphylactic shock
Localized: hives and eczema or atopy (an umbrella term covering clinical presentations of food allergy etc)
Delayed hypersensitivity reactions (>8hours after ingestion): cellular immunity involving T-lymphocytes and macrophages

10. What are stages of food allergy or hypersensitivity
A. Sensitization: initial meeting of an allergen and the immune system that results in IgE production
B. Activation of mast cells
IgE
Non-IgE substances (eg. Drugs)

12. Understanding Immunological concepts
Human body has many defense mechanisms to fight off infectious diseases and other toxic foreign substances.
Strong healthy adult human can fight off most of infectious diseases.
Ability to fight off disease can be modulated by genetics, age, race and lifestyles (diets, exercise and amount of sleep etc.)

13. Terminology Allergic reactions are Antigen-Antibody reactions
Antigen = a foreign substance
Antibody = a protein produced in response to an antigen that is capable of binding specifically to the antigen!
Haptens - a small molecule that has the ability to combine with an Ab or a cell-surface receptor.

14. Understanding Immunological concepts
Human body has two categories of defense system
Non specific defenses
Physical barriers (skin and mucous membrane)
Chemical barriers (saliva, mucus, gastric juices etc)
Cellular defenses (certain cells can eat invaders-phagocytes)
Inflammation (reddening, swelling and temperature increase of the affected sites)
Fever (elevated body temperature)
Molecular defenses (interferons or complementary system etc.)
Specific defenses or specific immunity**
Antibodies (many kinds of antibodies for many kinds of antigens)

15. Understanding Immunological concepts
Food allergies is related to specific defenses or specific immunity
Immune literary means “free of burden”
Actions of the immune system are triggered by antigens (foreign substances).
Most antigens are large protein molecules; Some antigens are polysaccharides and few are glycoproteins (carbohydrate and protein) or nucleo-proteins.

16. There are five classes of Immunoglobulins
1) IgG: Main class of antibodies in blood-also from mother-to-child (20%)
2) IgA: Small amount in blood, but larger amount in tears, milk, saliva, mucus and the lining tissues
3) IgM: First Antibody secreted during the primary response
**4) IgE (Reagin): Found mainly in body fluids and skin --- Associated with allergy reactions!
5) IgD: Found in B-Cell membrane

17. Nature of IgE Allergic Reactions
Antigen + IgE + Mast cells = Mediator release
Mediators= histamine and others

18. Who makes the immunoglobulin IgE?
The allergen enters the body and is recognized by sIg on a B-lymphocyte. The B-lymphocyte proliferates and differentiates into plasma cells that produce and secrete IgE against the allergen.
Picture credit: used with permission from Dr. Gary E. Kaiser

19. What’s next?
The next time the allergen enters the body, it cross-links the Fab portions of the IgE bound to the mast cell. This triggers the mast cell to degranulate, that is, release its histamine and other inflammatory mediators.
Picture credit: used with permission from Dr. Gary E. Kaiser

20. Nature of IgE Allergic Reactions
Antigen + IgE + Mast cells = Mediator release
Mediators= histamine and others
Picture credit: used with permission from Dr. Gary E. Kaiser

21. What does histamine do?
Vasodilation, increased capillary permeability, bronchoconstriction etc.

22. Symptoms-Food Allergy*
Nausea
Diarrhea
Abdominal cramps
Asthma/rhinitis
Vomiting
Hives
Laryngeal edema
Anaphylaxis

23. What are common allergenic foods?
Legumes (Peanuts and Soybeans)
Mollusks (snails, mussels, oysters, scallops, clams, squid)
Milk
Eggs
Fish (cod, salmon, haddock etc)
Crustacea (shrimp, crawfish, lobster etc.)
Wheat
Tree nuts (almonds, walnuts, Brazil nuts etc)
Selected food additives

24. It is not easy…living with food allergies!
What would you choose to eat, if
you are allergic to milk or dairy products?

25. Hidden food ingredients in ready made food products!
Milk and milk product derivatives
Egg and egg derivatives
Peanuts, tree nuts and derivatives
Fish derivatives (surimi, fish sauce, fish paste etc)
Soy and its derivatives

26. What about food Additives?
Sulfur-based preservatives
Sulfites
Aspartame (a sweetener)- PKU
Monosodium glutamate
FD&C Yelow #5 (Tartrazine)

27. How to deal with food allergy!
There is no specific antibody for any specific foods available!
People who have food allergy need a total avoidance of the offending foods.
Read food ingredient list.
Eliminate cross-contamination during cooking and preparation!!!!

28. Common medications prescribed by doctors
epinephrine (relaxes smooth muscle, constricts blood vessels, and stimulates the heart; used for severe systemic reactions);
antihistamines (block the binding of histamine to histamine receptors on target cells);
sodium cromolyn (prevents mast cells from releasing histamines).

29. Other causes of allergy-like food problems
Microbial products- e.g. histamine – Some food products have high levels of histamine (eg fermented foods)
Pharmacological reaction-tyramine, phenylethylamine, cafiene – dose dependent
Idiosyncratic reactions – (adverse reactions of drugs etc – dose dependent)
Psychological disorders

30. Food allergy and biotechnology
Although it is not easy to predict potential allergenicity of foods derived from GMO!, there are some criteria to go by:
Sources of transferred genetic material: While the crops from which staple foods are derived contain tens of thousands of different proteins, relatively few are allergenic.
Synthesis of allergenic proteins also depends on the growing conditions and other stress factors.
Molecular weight of most known allergens are between 10,000 and 40,000.

31. Are GMOs safe? Bt corn – US, 1996 Roundup® Ready Soybeans – US, 1996
Flavr Savr® tomatoes – US, 1994
“Golden Rice” – Switzerland, 1999

32. Bt-toxins present in peanut leaves (bottom image) protect it from extensive damage caused by
European corn borer larvae (top image)

33. 3-Enolpyruvyl shikimic acid-5-phosphate
Roundup Sensitive Plants
Shikimic acid + Phosphoenol pyruvate
3-Enolpyruvyl shikimic acid-5-phosphate
(EPSP)
Plant
EPSP synthase
Aromatic
amino acids
+ Glyphosate X X
Without amino acids, plant dies
EPSP synthase synthesizes 3-enolpyruvly shikimic acid-5-phosphate is the essential precursor to aromatic amino acids. When plants are sprayed with a glyphosate-containing herbicide, such as Roundup, this important precursor is not synthesized, and consequently the plant is starved of aromatic amino acids. The result is plant death. X X

34. Roundup Resistant Plants
Shikimic acid + Phosphoenol pyruvate
+ Glyphosate
RoundUp has no effect;
enzyme is resistant to herbicide
Bacterial
EPSP synthase
3-enolpyruvyl shikimic acid-5-phosphate
(EPSP)
With amino acids, plant lives
Roundup Resistant plants have a very simple solution. An engineered version of EPSP synthase, one that was discovered in a bacteria, is introduced into the plant. This enzyme can not be bound by glyphosate. Therefore, if a field is sprayed with the herbicide, the introduced version of the gene produces a functional enzyme. The 3-enolpyruvl shikimic acid-5-phosphate precursor is synthesized normally, and the plant produces enough aromatic amino acids to survive.
Aromatic
amino acids

35. Herbicide Resistance
Non-transgenics
Transgenics

36. Final Test of the Transgenic
RoundUp Ready Corn
Before
After

37. Golden Rice have been this obtained that accumulate of to 37 µg/g carotenoid
of which 31 µg/g is ß-carotene (as compared to the first generation where
only 1.6 µg/g were obtained in the greenhouse and 6 µg/g in average in a field trial).

38. Flavr Savr® Tomatoes
Calgene, Inc. developed a genetically modified tomato that was approved for market by the FDA in The Flavr Savr® tomato has an extra copy of a gene that codes for the enzyme polygalacturonase (PG), except it has been inserted in the antisense orientation (essentially, in backwards order). The PG enzyme is responsible for the breakdown of pectin within the cell walls of plants, which causes fruits to become soft as they ripen. By incorporating the antisense PG gene, the expression of PG in ripening fruit is decreased. The result of this genetic alteration is tougher skin.