Allergic cascade

If you have any form of Mastocytosis, it is important to be aware of the allergy cascade (otherwise known as the allergic cascade, or inflammatory cascade) to understand how each link in the chain works, which cells aside from the mast cell interact with allergies and what happens in the body at each step. This will help you better understand you can intercept, or treat, the cascade at its different stages.

Here are a couple of great videos, abeit simplified, on how the allergy chain works, and how anti-histamines can help:

Video 1: http://www.youtube.com/v/y3bOgdvV-_M&hl=en&fs=1& Video 2: http://www.youtube.com/v/ywdk3BTjK2s&hl=en&fs=1&

Here's a more indepth overview of the cascade (image below):

1. Allergen exposure for the first time 2. Antigen presenting cell gives allergen to T cell 3. T cell activates B cell 4. B cell releases "Y" shaped IgE allergen antibodies (IgE - immunoglobulin E) 5. IgE antibodies attach themselves to the FC receptors on the surface of mast cells and basophils and wait for the next exposure 6. Allergen exposure for the second time (sometimes years later) 7. Allergen affixes to IgE sticking out from the surface of the mast cell/basophil 8. Immune response cells degranulate, releasing mediators or chemicals (see mast cell for a list of these substances). 9. Mediators/chemicals cause systemic effects, such as vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction 10. Systemic effects result in individualised allergic response (from itchy nose, asthma, eczema through to anaphylaxis)



Intervention and treatment for each point in the chain
1. Avoid allergen 2. Emerging research on IgE and how it interacts with the FC receptor "will enable development of a new generation of allergy drugs that seek to interfere with the IgE-receptor interaction" (Ref 1) 2. A new treatment, omalizumab, a monoclonal antibody, recognises IgE not bound to its receptor and is used to neutralise or mop-up existing IgE and prevent it from binding to cells (Ref 1) 2. It may be possible to design treatments cheaper than monoclonal antibodies (for instance, small molecule drugs) that use a similar approach to inhibit IgE binding to its receptor (Ref 1) 2. In 1975 Robert N. Hamburger, M.D. published "Peptide Inhibition of the P-K Reaction" based on blocking up to 89% of the IgE receptors on mast cells by the pentapeptide representing amino acids 320 to 324 on the epsilon chain of IgE (Ref 1)

Ref 1: http://en.wikipedia.org/wiki/IgE The following journal article on the allergy cascade makes for interesting in-depth reading: http://www8.utsouthwestern.edu/vgn/images/portal/cit_56417/13/18/415119Education-_Allergic_Cascade.pdf The 2 phase allergic response diagram is from http://cdn.channel.aol.com/body/hv/101301