Hypersensitivity reaction or allergy, initially perceived as a secondary disorder, is now believed to be a major public health concern. For instance, contact dermatitis is a type IV delayed-type hypersensitivity reaction to skin allergens. An estimated 15%–20% of the general population has acquired contact allergy. To maintain immune tolerance, our immune system needs to differentiate between harmful non-self and innocuous non-self. Living organisms have developed during their evolution a set of biological mechanisms to protect them from the “outside”: physical barrier, inflammation, cell-based mechanisms, metabolism and elimination, and biochemical pathways such as glutathione. The innate and adaptive immune systems are also involved in the protection from the “outside” by mounting specific or non-specific responses leading to the clearance of dangerous triggers such as viruses, bacteria, or parasites. In the case of chemical or drug allergy, is our immune system clearing the danger resulting from environmental exposure to these harmful chemicals with a true immune response? Is the immune system then triggered specifically for its role: clearing a specific problem? Alternatively, should we perceive chemical or drug hypersensitivity as an accident with uncontrolled consequences leading to immunopathology?
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