Understanding Allergy

Question 1

general trends for allergies

Answer 1

1. Typically resolve by age 10.
2. Treenuts and peanuts = leading cause of fatal and near-fatal food allergy reactions.
3. cow’s milk and eggs is common young kiddie
4. seafood allergies are the most common in adults allergy

Question 2

What is an allergy?

Answer 2

It is an IMMUNE response mediated by immunoglobbin E. Remember that IgG is used to fight infections, very common. IgE is very rare in comparison. It is an antibody. It is found at interfaces between our bodies and the environment (mucous membranes (lungs, intestines, skin)). Only found in mammals (tho not all mammals have it). Fights against parasites (helminths)

Question 3

How do IgE trigger their responses?

Answer 3

They operate by triggering pro-inflammatory cells (basophils, as in mast cells.) on the FCeRI receptor (e = epsilon). When you have a IgE against a particular substance, that’s when you develop the symptoms.

Question 4

t/f you develop allergy on first exposure

Answer 4

f. need multiple exposers for the IgE to be made.

Question 5

Describe how to produce specific IgE

Answer 5

1. Eat something (chicken), digest it to proteins, which enter intestins. Protein = ALLERGEN.
2. Allergen enters intestinal epithelium and binds to APC. If they do not recognize it as something from the body, they go through sensitization process, where T cells mature to TH2 cells.
3. The TH2 cells interact with B memroy cells, which make IgE against the allergen that first invaded.
4. Upon allergen reentry, they contact IgE (crosslinking), which are linted to mast cells. Note that IgE is linked to FCeRI receptor.
5. Mast cell gets to work, driving inflammatory processes.
6. These mast cells can migrate to other parts of the body, spreading the symptoms there too.

Question 6

Describe the balance between TH1 and TH2 (T = T helper). How does it manifest in those with food allergies?

Answer 6

These are 2 classes of T helper cells. TH1 is stimulated by traditional infections (viruses, bacteria, protozoa). TH2 is triggered by parasites and foods. TH1 and TH2 regulate each other through inhibition. Those with food allergies have more TH2 than TH1, so TH1 is more inhibited.

Question 7

Treg cells

Answer 7

regulatory T cells that provide ANTI-inflammatory response.

Question 8

What causes the allergies humans have?

Answer 8

The proteins within those specific foods. ALL allergens are proteins.

Question 9

Name protein allergen associated to:
Peanuts:
Shellfish:
Cow milk:

Answer 9

Peanuts: Ara h 1-8 seed storage proteins
Shellfish: tropomyosin - muscle protein
Cow milk: lactalbumin - from lactos biosynth.

Question 10

What part of the allergen is responsible for the immune response? Explain epitope study. What do the dark squares represent? hat happens over repeated exposures to a given allergen?

Answer 10

Epitope This is the immunodominant fragment of the protein. These things bind to IgE and trigger the response. Dark squares int he study represent strong IgE response (increase in antibody presence). Repeated exposures increase the amount of epitopes that the patient reacts to on the protein, leading to stronger immune response.

Question 11

Explain cross-reactivity

Answer 11

Proteins with similar epitomes trigger similar immune response.

Question 12

Celiac disease.

Answer 12

Glucose intolerance. No IgE to gluten is involved to trigger the immune response. Instead:

1. Gliadin (Proline/glutamine rich peptide) found in wheat binds tightly to HLA type DQ2, driving immune response.
2. transglutaminases in gut deaminate the peptides from the glutin food, further strengthening HLA-DQ2 binding, leading to worse reaction
3. Transglutaminase can be crosslinked with gliadin peptide, leading to antibody formation against the peptide-bound couples and causing yet an even more sever autoimmune reaction
4. The proline-rich sequence of gliadin is resistance to protease digestions, increasing in concentration in small intestine, giving it a better chance to cause immune response.

Question 13

Describe how digestion interference triggers immune response.

Answer 13

1. low pH of stomach activates zymogens (pepsinogen to pepsin).
2. Antacids block pepsinogen-pepsin activation, leading a lot of nonfunctional pepsin.
3. This lack of pepsin inhibits food digestion. That allows the allergen epitomes to come through heavy and interact with your immune system,

Question 14

What is the difference between an allergen and a non-allergen?

Answer 14

Non-allergens have zero problems being digested. Allergens, specifically the epitomes kept in tact after stomach and intestinal enzyme run-through lead to an immune response. Note: the epitopes stay well folded in digestion proteases. the other components of the protein are digested. Also note that if protein is not digested within 4 hours, you likely have an allergy to that protein.

Question 15

What was learned from the mice allergy study?

Answer 15

Interaction between gut microbiota and proteins stimulates allergic response. If you increase microbioto growth (prebiotic), you increase allergic response. Likewise, if you increase presence of the allergen, you increase the response. Putting the allergen and microbiota growth factors (food) together stimulated the greatest response. High response = lowest bar on the graph.

Question 16

Describe relation between breast milk and allergies

Answer 16

It was discovered that breast milk has over 200 probiotic human milk oligosachs (HMO) which do not nourish the baby, but instead support gut bacterial growth. It was also discovered that bodies were getting the gut bacteria from the gut of the mother through her bloodstream into the mammary glands and into her breast milk. It was also discovered that HMOs prevent the growth of harmful factors by blocking their binding to intestinal mucosa.

Question 17

What was discovered by gastric acid suppression during pregnancy and childhood asthma study? What is the rational?

Answer 17

If mom takes antacid while pregnant, child had a 1.5 increased risk (as in 3x 50%…pretty significant) risk of developing childhood asthma. They excluded mothers who already had asthma. Time of exposure (1st or 3rd trimester) does not matter. same result.
Rational: taking antacids kills h pylori, among other microbacteria. The antacid seems to be killing strains of h pylori that are resistant to food allergies.

Question 18

Describe the outcoems of the commensal bacteria protect against good allergen sensitization study

Answer 18

1. Took mice, grew them in sterile environment without any microbiota.
2. INtroduced one microbiota
3. Tested and compared these mice to other sterile mice. Found that the mice with the singluar microbiota was resistant to more allergies than the mice with nothing (sterile). This was due to the singular microbiota’s increased presence in Treg to protect them.
   They also found that the B cells made as a result of the Treg switch classes, leading to production of IgA’s instead of IgE. Note that IgA works by catching molecules that try to pass through your gut, keeping them from going through.

Question 19

hygene hypotehsis.

Answer 19

Understimulation of TH1 results in higher stimulation of TH2. The understimulation of TH1 leads to understimulated Treg cells. In other words, increased exposure to the environment leads to decreased amount of allergies.

Question 20

Besides the hygene hypothesis, what else could lead to an increase in antibiotic production.

Answer 20

1. Antibiotics. They screw up intestinal flora.

2. Food additives may be increasing susceptibility to developing an allergy.

Question 21

How do you treat an allergy?

Answer 21

Oral immunotherapy, which involves putting small amount of allergen under tongue, stimulating treg cell production. This would lead to a decreased immune effect. IgE levels actually would go down and IgG levels increase (blocks effects of allergen)

2. using molecule antibodies (mABs) against IgE or FCeRI broadly to reduce sensitivity to range of antigens, including most prevalent food allergens.
3. Designing proteins with bind to IgE heavy chain domains in order to dissociate the IgE from the receptor.