Prologue: Innate Immune Tools to Defend Against Stressful Injury: Success and Failure
In the prologue of Part V, the scenario of a continuous struggle for life of all organisms on earth against internal and environmental stressful and injurious conditions is cursorily sketched. Eukaryotic cells are not only intrinsically engaged in taking care for transient adaptations that typically occur in response to relatively mild changes in conditions. They must also continuously adapt to fluctuations in external conditions associated with heavy perturbing and insulting stimuli. Whereas severe injuries may lead to an immediate accidental cell death associated with passive release of DAMPs, moderate injuries may initially result in DAMP-induced stress responses including the heat shock response, the unfolded protein response, and the DNA damage response, the aim being to restore homeostasis. However, when unsuccessful, these stress responses result in a controlled destruction of the stressed cell known as regulated cell death, one typical subroutine form being regulated necrosis. This type of cell death is associated with (1) active secretion of inducible DAMPs during the dying process, followed by (2) passive release of constitutive DAMPs after final rupture of the plasma membrane. Both constitutive and inducible DAMPs evoke cell-extrinsic efferent innate immune responses in terms of inflammation and inflammation-related events such as phagocytosis and may elicit subsequent antigen-specific adaptive immune responses. The complex scenario of these hierarchical interrelationships between stress responses, types of regulated cell death, and emission of DAMPs is outlined in this part of the book in the form of a streamlined text.