Hypersensitivity Haptenes

An argument against an immunologic reaction in non-immediate hypersensitivity reactions has been the lack of a hapten. Non-ionic RCM are chemically non-reactive... 

In addition to tumor immunity, UV exposure was found to impair antigen presenting cell function, the generation of contact hypersensitivity (CHS) to chemical haptens and... 

Shimizu, T., Munn, C. G., and Streilein, J. W., Transepidermal induction of contact hypersensitivity in mice with a water-soluble hapten, J. Invest. Dermatol. 101, 749-753, 1993. 

A classic mechanism by which some reactive metabolites are believed to mediate hypersensitivity reactions is by acting as a hapten (i.e., the reactive metabolite binds to... 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

It is believed that nickel penetrates the skin and acts as a hapten, complexing with selected peptide and/or amino-acid ligands to distort intercellular or cellular proteins, stimulating a type IV delayed (cell-mediated) hypersensitivity reaction [398]. Nickel water-soluble salts, like nickel chloride and nickel sulphate, are strong sensitizers [213, 215], The chloride induced in sweat is apparently an important factor in dissolving the metallic nickel, permitting the soluble nickel salts to act. 

A rare but serious event that can result from irreversible CYP inhibition is the development of a hypersensitivity reaction. The bioactivation of a drug and the formation of a covalent adduct between the activated substrate and the enzyme can lead to hapten formation and eventually to an idiosyncratic autoimmune response (usually in the form of autoimmune hepatitis) [14]. The hapten formation is the first key step toward the autoimmune response. The CYP macromolecule is made immunogenic ( foreign ) by the covalent binding of the electrophilic metabolites, and the immune reaction follows with the production of autoantibodies against the target molecule (not necessarily alkylated). 

Contact Hypersensitivity and Animal Model of Tolerance to Haptens... 

Xenobiotics can affect allergic disease in one of two ways. They can themselves act as antigens and elicit hypersensitivity responses, or they can enhance the development or expression of allergic responses to commonly encountered allergens, such as dust mite. Chemicals that act as allergens include certain proteins that can by themselves induce an immune response and low molecular weight chemicals (known as haptens) that are too small to induce a specific immune response but may react with a protein to induce an immune response that is then hapten specific. Haptens have been associated with both allergic contact dermatitis (ACD), sometimes called contact hypersensitivity... 

Halothane (149), first used clinically in the 1950s, is some three times more potent than ether and onset of anesthesia is rapid. Mild, transient hepatotoxicity occurs in about 20% of patients. A much rarer but more severe toxicity has been attributed to a drug-induced hypersensitivity reaction. Under aerobic conditions, halothane is oxidatively metabolized to trifluoroacetyl halide that apparently acylates tissue molecules. The bound trifluoroacetyl moiety functions as a hapten in sensitive individuals triggering the immune response253. 

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