Food Allergies

Question 1

Food allergy

Answer 1

Adverse health effect arising from a specific IMMUNE RESPONSE that occurs REPRODUCIBLY on exposure to a given food

Can be IgE-mediated or non-IgE mediated

Question 2

Food intolerance

Answer 2

Non-immunologic adverse reactions to foods

Ex: lactose intolerance, rxns to food additives/preservatives, pharmacological effects of caffeine

Question 3

Food sensitization

Answer 3

Presence of food-specific IgE

NOT equivalent to food allergy - just bc you have specific IgE doesn’t mean you’re allergic to the food

Question 4

Most common food allergens in USA

Answer 4

Milk, eggs, peanuts

Question 5

Risk factors for food allergy

Answer 5

atopic dermatitis (eczema)

sibling w food allergy (peanut)

delayed dietary introduction (pearnut)

Question 6

Two phases of Development of Food Allergy

Answer 6

(1) Allergen sensitization

(2) Mast cell activation

Question 7

Allergen sensitization (process)

Answer 7

1. First exposure to food allergen: taken up through GI tract and phagocytosed by Dendritic cell
2. Dendritic cell travels to lymph node; presents antigen to Naive CD4+ T cell
3. Activated CD4+ T cell differentiates into IL-4 producing Tfh cell – stimulates B cell to class switch and make IgE against the antigen
4. B cell turns into an IgE-secreting plasma cell that secretes peanut-specific IgE
5. IgE produced by B cell binds to FcgammaR receptors on mast cells

The Mast cell is now “primed” or ready for antigen (peanut) bonding for the second exposure

Question 8

Mast cell activation (process)

Answer 8

1. Upon next exposure to antigen, the binding of the antigen (peanut) to the IgE (already bound to the Fc receptor of mast cell) ACTIVATES the mast –> degranulation
2. Activated mast cell releases a variety of mediators: (1) Vasoactive amines, lipid mediators and (2) Cytokines

Question 9

Function of Vasoactive amines, Lipid mediators released by mast cells

Answer 9

Immediate hypersensitivity reaction (minutes after repeat exposure to antigen)

Question 10

Function of Cytokines released by mast cells

Answer 10

Late-phase reaction (2-4 hours after repeat exposure to antigen)

involves recruitment of inflammatory cells

Question 11

IgE

Answer 11

• Low levels in plasma (<1 microg/ml)
• Elicited by allergens in atopic individuals (IL-4 production by allergen-specific T helper cells stimulate B cell antibody class switching to IgE)
• Binds to high-affinity Fc epsilon receptor (FcepsilonR) on mast cells and basophils

Question 12

Fc epsilon Receptor

Answer 12

• Highly expressed on mast cells and basophils
• Very high affinity for IgE (full receptor occupancy under normal conditions)

-Composed of:
1 alpha chain (IgE binding)
1 beta chain and 2 gamma chains (Signal transduction)

Question 13

Mast cells

Answer 13

Found in Tissues

• derived from bone marrow precursors
• located in mucosal and connective tissues
• express high levels of FC epsilon receptor
• Granules contain preformed mediators that are rapidly released upon activation (degranulation)

Question 14

Growth factors for Mast cells

Answer 14

stem cell factor, IL-3

Question 15

Inflammatory mediators produced by Mast cells upon activation

Answer 15

Lipid mediators (prostaglandins, leukotrienes)

Cytokines (TNFalpha)

Question 16

Basophils

Answer 16

Found in Blood

• derived from bone marrow precursors
• rare; found in circulating blood (<1%)
• recruited to tissues during allergic inflammation
• express high levels of FC epsilon receptor
• exact role in immediate hypersensitivity rxns unclear

Question 17

Growth factors for Basophils

Answer 17

IL-3

Question 18

Eosinophils

Answer 18

Recruited to tissues during late-phase of allergic response

• derived from bone marrow precursors
• found in circulating blood (2-4% blood leukocytes)
• increased during allergic disease and parasitic infections

Question 19

Growth factors for Eosinophils

Answer 19

IL-5

Question 20

Major granule contentes of Eosinophils

Answer 20

Major basic protein, eosinophil cationic protein

enzymes that cause tissue damage (peroxidases, hydrolases, lysophospholipases)

Toxic to microbes and host tissues

Question 21

Mast cell activation by allergen upon second exposure

Answer 21

Allergen-triggered cross-linking of IgE-Fc epsilon Receptor complexes results in mast cell activation and degranulation

Question 22

Outcomes of Mast cell activation

Answer 22

(1) Granule release of vasocative amines and proteases (leads to vascular dilation/smooth muscle contraction and tissue damage)
(2) Enzymatic modification of AA leading to secretion of lipid mediators (Prostaglandins for vascular dilation and LTs for smooth muscle contraction)

Later….
(3) Transcriptional activation of cytokine genes leading to cytokine release (results in inflammation and leukocyte recruitment)

Question 23

Allergic responses consist of _______ and ________ reactions

Answer 23

immediate; late-phase

Question 24

Immediate phase of Allergic response

Answer 24

Release of preformed vasoactive mediators by mast cells

• vasodilation
• swelling (edema)
• itching (pruritus)
• bronchoconstriction
• intestinal hypermotility

Question 25

Late phase of Allergic response

Answer 25

Production of cytokines and chemokines - accumulation of inflammatory cells (eosinophils, basophils, T cells) - tissue inflammation

Question 26

Benefits of Skin prick testing

Answer 26

- High sensitivity but moderate specificity (lots of false positives) - Rapid and safe

Question 27

Treatment for food-induced anaphylaxis

Answer 27

Intramuscular epinephrine (first and most important) Bronchodilators for wheezing/bronchospasm Antihistamines, gluccocorticoids

Question 28

Oral allergy syndrome (i.e. pollen-food allergy syndrome)

Answer 28

- Presents in adolescents/adults with allergic rhinitis (hay fever) - IgE-mediated rxn against pollen-related proteins in food - can cook food to degrade allergens

Question 29

Food-dependent exercise-induced anaphylaxis

Answer 29

development of anaphylaxis symptoms during exercise that occurs within a few hours of eating a specific food

Question 30

Delayed allergic reactions to mammalian meat

Answer 30

Due to IgE specific for the carbohydrate "alpha-gal" Allergic symptoms occur 4-6 hrs after consuming mammalian meat

Question 31

IgE-mediated food allergy is a type of

Answer 31

immediate hypersensitivity reaction

Question 32

Symptoms of IgE-mediated food allergy

Answer 32

Cutaneous symptoms (urticaria, angioedema, flushing, itching) Gastrointestinal symptoms (vomiting, severe nausea and abdominal cramping) Respiratory symptoms (rhinorrhea, laryngoedema, dyspnea, wheezing/bronchoconstriction) Cardiovascular symptoms (lethargy, hypotension, syncope)