Figure 22.

The Okamoto model for necrotic cell death (adapted from Ref. 96). The Okamoto model, originally proposed as a unifying model for β-cell damage and its prevention, well explains both how autoimmunity for β-cell necrosis is initiated and how necrotic cell death is involved in various diseases in many tissues other than β-cells. Under physiological conditions, apoptotic cell death constitutively occurs for renewal and maintenance in animal bodies, whereas necrotic cells initiate and enhance (auto)immune reactions under pathological conditions. On the other hand, apoptotic cells recognized by macrophages/dendritic cells inhibit phlogistic (auto)immune responses. For the initiation of massive and pathological apoptotic cell death, necrotic cell death, which triggers autoimmune responses in macrophages/dendritic cells, is required.