Lecture 24: Food allergy, when oral tolerance does not develop Flashcards
What is the worst allergies you can have as a kid?
Milk, wheat and peanuts
What does exposure of milk in cupcake look like in an allergic child?
- Stridor
- vomiting
- hives
What is stridor?
High-pitched wheezing sound resulting from turbulent air flow in upper airway
How many mg of protein in a peanut?
300 mg
Children can develop reactions to as little as 5mg
How many people in the US have food allergy?
12 million
What allergies can you outgrow?
Wheat
Milk
Egg
Soy
What are the types of adverse food reactions?
- Food intolerance
- food allergy
Focus is only on IgE-mediated allergies
What is the presentation of IgE mediated reactions?
- Cutaneous reactions
- hives
- swollen lips
- swollen tongue
- can have anaphylaxis WITHOUT skin findings
- GI
- nausea
- vomiting
- diarrhea
- abdominal pain
- Respiratory
- runny nose
- sneezing
- congestion
- cough
- wheeze
- inability to breath
- Multiorgan symptoms
- neurologic
- cardiologic
Do you need skin problems for anaphylaxis?
No
How do you treat anaphylaxis?
Epinephrine
How does epinephrine work?
- Alpha adrenergic properties
-vasoconstriction, increased blood pressure, decreased capillary leak - Beta adrenergic properties
-relax bronchial smooth muscl, increase heart rate, increase cardiac contractility
Inhibits mediator release?
What is the mechanism for anaphylaxis?
Complex interaction among food, APC, T cells and B cells, activation of IgE Initial response -vasodilation -vascular leakage -smooth muscle spasm Late-phase response -mucosal edema -mucus secretion -leukocyte infiltration -epithelial damage -bronchospasm
What is the largest immunologic organ in the body?
GI tract
What is oral tolerance?
State of active inhibition of immune responses to an antigen by means of prior exposure to that antigen through oral route
Development of tolerance is difference between those with and without food allergy
Where can food antigens be absorbed?
Stomach
Small bowel
Colon
What are the cells that mediate the complex homeostasis of GI tract?
- Intestinal epithelial cells (IEC)
- Dendritic cells (DC)
- T regulatory cells
What are characteristics of a food allergen?
Dose and form of antigen matters
Most are small and resistant to thermal and chemical denaturation
Solubility in water
Linear epitopes??
How many antigens get through the intestinal lumen?
2% of food antigens get through
Normally, presentation of antigen by intestinal epithelial cells leads to inactivation/suppression of immune response
If antigens do get through, they are taken up by dendritic cells found in lamina propria, peyers patches and mesenteric lymph nodes
DC then interact with T regulatory cells, which secrete TGF-beta and Fox P3 cells
What does IgA do to food allergens?
They inhibit absorption of antigens
What do M cells do?
Found in dome overlying Peyer’s patches
Take up antigen due to LIMITED glycocalyx, sparse cytoplasm and high endocytic activity
Delivers antigens to underlying immune cells
What is the significance of t regulatory cells in allergies?
Play a pivotal role in directing balance between tolerance and active immunity
In mice, what are the two different types of tolerances?
- Low dose tolerance
-repeated lower dose, activates regulatory T cells - High dose tolerance
-mediated by deletion or lymphocyte anergy
-via single high dose
-in humans, thought to be via anergy
If these do not occur, there exists inflammatory responses
What is Hypersensitivity?
Failure to develop or a breakdown in oral tolerance may result in hypersensitivity responses to antigen
- B cells produce food specific IgE - cross linkage upon exposure
How many children develop tolerance?
80%
We don’t know why
