Haptens (derived from the Greek haptein, meaning “to fasten”) are small molecules that elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself. The mechanisms of absence of immune response may vary and involve complex immunological interactions, but can include absent or insufficient co-stimulatory signals from antigen-presenting cells.
Haptens have been used to study allergic contact dermatitis (ACD) and the mechanisms of inflammatory bowel disease (IBD) to induce autoimmune-like responses.
The concept of haptens emerged from the work of Austrian immunologist Karl Landsteiner,
who also pioneered the use of synthetic haptens to study immunochemical phenomena.
Haptens applied on skin, when conjugate with a carrier, could induce contact hypersensitivity, which is a type IV delayed hypersensitivity reaction mediated by T cells and dendritic cells. It consists of two phases: sensitization and elicitation. The sensitization phase where the hapten is applied to the skin for the first time is characterized by the activation of innate immune responses, including migration of dendritic cells to the lymph nodes, priming antigen-specific naive T cells, and the generation of antigen-specific effector or memory T cells and B cells and antibody-secreting plasma cells. The second elicitation phase where the hapten is applied to a different skin area starts with activation of effector T cells followed by T cell-mediated tissue damage and antibody-mediated immune responses. Haptens initially activate innate immune responses by complex mechanisms involving inflammatory cytokines, damage-associated molecular patterns (DAMP), or the inflammasome.
Once the body has generated antibodies to a hapten-carrier adduct, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this.
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