Nanda - Food Allergy Flashcards
How does IgE cause allergic reactions to occur?
You eat the allergen, which eventually gets into the lumen of the SI. It then can get taken up into the SI epithelium and interact with the immune system. The allergens will get engulfed by an allergen presenting cell and then presented onto the MHC receptors. These interact with the T cell, and then T helper cell, and then a B cell is made and programmed. The B cells are responsible for making specific immunoglobulins towards the allergen
At what point will we actually have the allergic reaction? In other words, we might not have an allergic rxn the first time we eat something,g but later on we might. What causes that?
Remember, each time you eat the food you are making more antibodies against that food. These antibodies bind to the FCepsilonRI receptors present on the cell. Once all of these receptors are saturated, the mast cell will release its contents and initiate an allergic response.
TH1/TH2 balance hypothesis
The ratio of TH1:TH2 dictates whether or not you will have an allergic response.
- TH1 reacts to infections
- TH2 reacts to parasites
- – this is the one that we have been describing that causes the mast cells to e activated, eosinophils, and B cells to be made.
- TH1 and TH2 antagonize each other so if levels of one get high, its products might inhibit the other one.
How does celiac disease work?
Gliadin is a proline/glutamine peptide that is found in wheat. It strongly binds to HLA type DQ2, which drives an immune response due to direct binding to MHC.
- activation of tissue transglutaminase makes HLA-DQ2 binding more potent.
- Transglutaminase also can cross link with gliadin peptides, resulting in antibodies against peptide-bound complex and leading to a stronger autoimmune reaction.
IT IS NOT A IgE MEDIATED RESPONSE TO A FOOD PROTEIN BUT RATHER AN IMMUNE RESPONSE TO A PROTEIN NONETHELESS
WHy might taking antacids cause a patient to become allergic to something?
Because you are raising the pH of the stomach, so peptidases might not get activated properly. This allows large peptides to stay undigested and become an allergen.
which class of bacteria conferred allergen resistance? How did they find this out?
Clostridia class - they Had gnotobiotic mice and slowly introduced bacteria to them and figured out that it was the clostridia class that was responsible for allergen resistance.
- we also saw changes in the intestinal themselves in that clostridia support expansion of Treg cells, which are responsible for creating tolerogenic responses. There was also a higher concentration of IgA, which essentially bind up allergens and don’t allow them to get into the epithelium.
What are some of the “treatment therapies” for allergies?
1) Avoidance is Usually best option
2) Oral immunotherapy - put small amounts of allergen under the tongue
- this causes a significantly reduced response to allergen in the future
- IgE levels go down
- IgG levels go up and block IgE from binding to it
- Treg levels go up
3) Monoclonal antibodies against IgE or FCepsilonRI reduce the sensitivity to a range of antigens by blocking this interacting.
4) designing proteins that will prevent the antibody from interacting with the mast cells. Allosteric binding of IgE heavy chain domains can dissociate IgE from the receptor.
What immunoglobulin is most heavily involved in allergic rxns?
In order to be a real allergic response it has to be mediated by IgE.
- they are relatively little in number but confer the greatest inflammatory response.
- they bind tot basophils/mast cells and cause them to release their pro-inflammatory cytokines.
- only found in mammals
- found in the lungs, intestines, and skin
- They confer defense against parasites.
What does TH1 make? What does TH2 make?
TH1 - macrophages
TH2 - eosinophils, mast cells, IgE
What broad class of macronutrient is generally responsible for food allergies?
Proteins
what is an epitope?
Region of the protein that IgE acts on.
What is transglutaminase role in celiac?
Transglutaminase can alter the gliadin into a form that can bind to the MHC even tighter, causing an even greater immune response.
In addition, in the most severe forms of the disease, Transglutaminase can crosslink with gliadin, thus causing even tighter binding and causing your body to attack your own transglutaminase.
What is unique about gliadin that causes so many issues?
It is a proline-rich sequence and therefore the body has difficulty breaking it down. Therefore, the gliadin stays in the gut for longer periods of time and allows the full immune response to occur.
What experiment was done to show that only tropomyosin from shellfish and not other animals are potentially harmful?
Firstly they saw that shellfish tromopyosin was not fully degraded in the stomach whereas other species tropomyosin was.
Then, they were able to show that certain peptides, which they were able to determine by mass spec, did not get readily degraded.
Therefore, there must be something about tropomyosin from shellfish that ensures that it is not readily digested.
How did they use molecular dynamics to show which parts of the protein were most resistant to breakdown?
Basically what they do is take what they think thhe molecule looks like in solution and then using a computer program they see which parts of the protein fall apart over time and which parts stay strong over time. The ones that stay strong over time happen to also be the epitopes.
