Danger signals and skin sensitization

Sir, We read with great interest the recent topical review by Dr English1 in which he considered the influence of exposure (dose per unit area) and the availability of 'danger signals' on the development and clinical investigation of allergic contact dermatitis. In the spirit of scientific dialogue we thought it would be interesting to explore further what Dr English had to say about danger signals and the relevance of these for the induction of skin sensitization. The danger hypothesis as articulated by Matzinger2 has had a major, but controversial, impact on how the operational basis for adaptive immunity is viewed. A central premise has been that a cardinal characteristic of immune function is the ability to discriminate between 'self' and 'non‐self'. However, it is apparent that this paradigm cannot necessarily accommodate all features of adaptive immunity; many 'foreign' antigens to which there is considerable and sustained exposure are tolerated (food and commensal bacteria), while 'self‐antigens' may be the target of responses in autoimmune disease. In attempting to resolve these and other apparent anomalies the danger hypothesis argues that it is not foreignness per se that is the key element in provoking an immune response, but rather the changes associated with cell or tissue damage. In effect, the model is based on the view that control of immune activation is essentially effected by endogenous, rather than exogenous, signals.3 In the context of contact sensitization it is relevant that antigen‐presenting cells, and in particular dendritic cells (DCs), may play a central role in sensing danger signals within the local microenvironment.4, 5