Drug-related allergic reactions are hypersensitivity reactions mediated by the immune system and unrelated to the drug's therapeutic action. Drugs, by themselves, do not provoke an immune response. However, they may combine with endogenous proteins to form antigens, which induce lymphocytes to produce antibodies. IgE-type antibodies fix themselves on mast cells. Subsequent re-exposure to the same stimulus triggers the antigen-antibody interaction, liberating several mediators that produce type I allergic reactions. The reaction targets the skin, GI tract, and respiratory system. Type II reactions involve IgG and IgM antibodies that interact with drug-altered host cells. The interaction activates the complement. Type III reactions are mediated by antibodies bound to soluble antigens, also called immune complexes. They activate the complement and stimulate the release of mediators that cause inflammatory responses. Type IV reactions involve a sensitization phase that produces activated T-cells. These release cytokines, which recruit macrophages and neutrophils to generate an inflammatory response.