Food Allergies Flashcards
Food allergy
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
Food intolerance
Non-immunologic adverse reactions to foods
Ex: lactose intolerance, rxns to food additives/preservatives, pharmacological effects of caffeine
Food sensitization
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
Most common food allergens in USA
Milk, eggs, peanuts
Risk factors for food allergy
atopic dermatitis (eczema)
sibling w food allergy (peanut)
delayed dietary introduction (pearnut)
Two phases of Development of Food Allergy
(1) Allergen sensitization
(2) Mast cell activation
Allergen sensitization (process)
- First exposure to food allergen: taken up through GI tract and phagocytosed by Dendritic cell
- Dendritic cell travels to lymph node; presents antigen to Naive CD4+ T cell
- Activated CD4+ T cell differentiates into IL-4 producing Tfh cell – stimulates B cell to class switch and make IgE against the antigen
- B cell turns into an IgE-secreting plasma cell that secretes peanut-specific IgE
- 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
Mast cell activation (process)
- 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
- Activated mast cell releases a variety of mediators: (1) Vasoactive amines, lipid mediators and (2) Cytokines
Function of Vasoactive amines, Lipid mediators released by mast cells
Immediate hypersensitivity reaction (minutes after repeat exposure to antigen)
Function of Cytokines released by mast cells
Late-phase reaction (2-4 hours after repeat exposure to antigen)
involves recruitment of inflammatory cells
IgE
- 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
Fc epsilon Receptor
- 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)
Mast cells
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)
Growth factors for Mast cells
stem cell factor, IL-3
Inflammatory mediators produced by Mast cells upon activation
Lipid mediators (prostaglandins, leukotrienes)
Cytokines (TNFalpha)
Basophils
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
Growth factors for Basophils
IL-3
Eosinophils
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
Growth factors for Eosinophils
IL-5
Major granule contentes of Eosinophils
Major basic protein, eosinophil cationic protein
enzymes that cause tissue damage (peroxidases, hydrolases, lysophospholipases)
Toxic to microbes and host tissues
Mast cell activation by allergen upon second exposure
Allergen-triggered cross-linking of IgE-Fc epsilon Receptor complexes results in mast cell activation and degranulation
Outcomes of Mast cell activation
(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)
Allergic responses consist of _______ and ________ reactions
immediate; late-phase
Immediate phase of Allergic response
Release of preformed vasoactive mediators by mast cells
- vasodilation
- swelling (edema)
- itching (pruritus)
- bronchoconstriction
- intestinal hypermotility