In the context of chronic asthma, which underlying conditions might allow non-immunologic stimuli to contribute to the pathology of type I and type IV hypersensitivity reactions?
1) Events leading to epitope spreading
2) Progressive increase in serum IgE levels with repeated allergen exposure
3) Events leading to a switch from a TH2 to a TH1 response
4) Irreversible remodeling of the stroma caused by chronic inflammation
5) Altered TLR expression on dendritic cells