Some allergies can be treated by a procedure called desensitization

Question

A. Explain two current approaches to desensitization.
B. Explain the main disadvantage associated with each.

Answer 1

(i) One approach to desensitization is the subcutaneous injection of the allergen itself into sensitized individuals with the aim of skewing the immune response from an IgE to an IgG4 isotype. This is achieved by gradually increasing the subcutaneous allergen concentration over time, which favors IgG over IgE production. When antigen is encountered subsequently, IgG will compete with IgE for binding and inhibit IgE cross-linking on mast-cell surfaces. (ii) The second approach involves vaccination with allergen-derived peptides designed to be bound by HLA class II molecules and presented to allergen-specific TH2 cells with the aim of inducing anergy in these T cells. This would prevent them from giving help to allergen-specific naive B cells, thus preventing the production of more IgE antibody on repeated exposures to the environmental allergen.
B. (i) A risk of the first approach is the possibility of activating a systemic anaphylactic response after mast-cell activation. Because the patient was previously sensitized, IgE antibodies against allergen are present and, if bound to mast cells, will induce mast-cell degranulation. In the event of an anaphylactic response to an allergy shot, the patient will have epinephrine administered immediately by the attending physician or nurse practitioner. (ii) With the peptide vaccination approach, allergen-specific T cells are rendered anergic and there is no risk of triggering an anaphylactic reaction. However, the disadvantage of this approach is that because the HLA class II genes are highly polymorphic, the vaccine would have to include sufficient peptides able to bind to most HLA class II allotypes, or it would need to be custom made for each individual on the basis of their HLA class II type.