Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

Figure 1

The likely pathway of the “sensitization” phase of contact hypersensitivity. (a) Hapten application induces strong innate immune mechanisms, causing cell death and the release of danger signals and endogenous ligands, leading to cytokine release, IL-1β, IL-18, TNFα, and GM-CSF, by keratinocytes (KC). This release will stimulate dermal antigen-presenting cells (dAPCs), langerhans cells, and dermal dendritic cells, to take up haptenated antigen and migrate to the dLN to activate naïve T-cells. Mast cells will aid in this migration by releasing TNFα. (b) iNKT cells in the liver will be activated by APCs presenting haptenated glycolipid by CD1d. This will cause cytokine release, IL-4, to stimulate naïve B-1 cells in the peritoneal cavity, along with the binding of hapten-antigen by membrane IgM. This will cause migration of these cells to the dLN, and subsequent maturation into CS-initiating B-1 cells, which release antihapten IgM into circulation.