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I think have a functional understanding of how an allergic reaction (Type I Hyper Sensitivity) occurs: basically the allergen causes production of antibodies that attach to mast cells and basophils. Later, if the same allergen binds to those antibodies, the cells release histamine and other unpleasant chemicals.

However, it's clear that the degree of allergic reaction varies a lot from person to person. For example, if my wife goes outside all day during peek grass pollen season, she'll end up with a sinus reaction, and not much else. If I go outside for a few minutes, I'll develop that, and if I stay longer, I'll get hives, weepy eyes, and so on.

Clearly I'm more sensitive to grass than my wife, but what exactly causes this? I can imagine a lot of possible factors!

  • Maybe I have many more antibodies (but why?)
  • Maybe I absorb more of the allergen per unit time (but why?)
  • Maybe my mast cells require less allergen to react (but why?)
  • Maybe my mast cells contain more histamine per cell (but why?)
  • ...

So I guess my question is: What drives the variation in allergic hyper sensitivity responses?

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Network of possible factors that contribute to the variability of the immune reaction between individuals is still not well investigated.

Type I hypersensitivity is mediated by IgE antibodies, which means that lymphocytes B after initial contact with antigen undergo oligoclonal selection. Only these with the highest affinity towards the antigen will survive. During this process (see: germinal centre reaction) genomic regions responsible for antigen binding change their sequence in non-deterministic manner. So, each individual has slightly different set of antibodies targeting the same antigen.

Moreover, within the same antigen (allergen), different regions (epitopes) can trigger the immune reaction in different individuals.

Other, more general factors also contribute to the symptoms associated with hypersensitivity reaction. For example: hormones, infections, medications, microflora condition, genetics (eg. major histocompatibility complex) or even psychological status.

Also see: Article 1 Article 2 Article 3

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