Lecture 23

common food allergies

soy, wheat, eggs, milk, tree nuts, peanuts, fish, shellfish

90% of allergic responses are to these

hundreds of others make up the remaining 10%

food allergen labels

cross contact allergens

occurs during processing

residues or trace amounts of an allergenic food

unintentionally incorporated into another food

need to label these too

food allergy signs and symptoms

incidence of food allergy

in NZ have food allergy in 10% of infants, 4-8% of children, 2% of adults - lots of people grow out of it as the immune system matures

Genuine increase - we still don’t really know why

Increase number of people being diagnosed and people being hospitalised (more serious responses)

Why are we becoming more allergic to stuff? We don’t know

the allergic march

kids with food allergies often develop other atopic conditions too

effective treatment for food allergy - reduction in other conditions?

definitions of food allergy

inappropriate immune response to food ingestion

immune response to protein antigens in food

note that most people arent allergic but the body doesnt just ignore food allergens it just deals with them properly - Gut is always testing food that is coming in and produces a regulatory immune response - appropriate immune response through generation of Tregs

If you have an allergy this response is inflammatory rather than regulatory - dendritic cells signal to T cells to become activated

predominant in early age - many people grow out of it as the immune system develops

mechanisms of food allergy

allergic response - Th1-parasite response = IgE mediated

healthy respnse - Tregs, tells the immune response to ignore the antigen

two mechanisms of food allergy

IgE mediated (most)

not IgE (complex)

IgE

most bound to IgE receptors on granulocytes - eosinophils and mast cells

binding to IgE bound to mast cells triggers degranulation and immediate type hypersensitivities

eosinophil degranulation

 

IgE binds to eosinophils and basophils and to the surface antigens of the parasite

Crosslinking triggers degranulation - toxic chemicals released to destroy the parasite

summary of immune response to parasites

1. immune reponse takes signals from pathogens and prgrammes trhe entire immune response to be best for destroying that antigen

2. T cells make cytokines to activate other cells and kill stuff

3. B cells make antibodies that bind to stuff

4. allergy responses are a hypersensitivity immune response

5. IgE is the type of antibody most commonly mediating allergic responses (there are other types)

6. IgE was designed for parasite infections

7. IgE degranulated eosinophls and mast cells

8. the granules activate lots of pathways that help to expel a parasite

9. the granules are responsible for the allergy symptoms

IgE mediated food allergy - 1

food specific IgE binds to cells wearing high affinity Fc receptors including mast cells and basophils and eosinophils

IgE mediated food allergy - 2

mast cells have large preformed grnaules contatinign proinflammatory and vasoactive mediators

IgE mediated allergy - where do masyt cells live

in skin and mucus

IgE mediated antibody - 4

binding of allergen cross links IgE bound to mast cell FcR → rapid degranulation

IgE mediated food allergy - pathology (5-9)

release of histamine leads to contraction of smooth muscles and induces vmiting; transepithelial fluid loss into gut lumen leads to diarrhea

allergne absorbed into blood stream or gut mucus reaches connective tissue mast cells associated with blood vessle, degranulation here leads to uticaria (hives)

widespread degranulation can result in systemic anaphylaxis and shock and death

histamine increase in vascular permeability results in drastic loss of blood pressure and airway constriction

swelling of epiglottis blocks breathing

epinephrine injection inhibits smooth muscle contraction and vasodilation

IgE mediated food allergy - summry diagram

detail not needed

IgA mediated food allergy

T cell plasticity and redundancy in food specific IgA production

exposure to allergens - immune memory

second exposure generates a much bigger and better immune response than first exposure

allergy - first exposure probably mild reaction (not noticed)

second exposure is serious

why are people allergic

genetic basis

breakdown in oral tolerance (the ability to eat food and not generate an immune response)

sensitisation to food allergens

environment

genetic basis of allergy

heritability of predisposition to allergic diseases siggest a genetic basis - up to 82% of food allergy

no candidate susceptibility genes identified

breakdown in oral tolerance

oral tolerance means that ingested food proteins do not elicit a specific immune response - mechanisms still unclear, difficult to study in vivo because studying absence of effect

APCs - specialised DCs pick up food antigens and take them to lymph nodes and activate Tregs

Tregs - activated by food antigens = suppressed immune response (still allergen specific)

sensitisation to food allergens

majority of peanut allergic children experience their first allergic reaction to peanut on first known ingestion

must have a non-oral exposure somehow to generate immune memory

• in utero

• household non oral

• via skin

• external factors that enhance sensitisation (vitamins, folate, AHR ligands), microbiota

environmental factors