Abstract
In this Issue, two highly important reviews are published, one on NK cell biology and the role of NK cells in cell death, and the other one on a phenomenon called the Shwartzman reaction, which had been first described by Gregory Shwartzman in the 1920s as dermal necrosis that resulted from intradermal injections (one priming and one challenging 24 h later) of sterile culture filtrates from Gram-negative bacteria into normal rabbits. Successive histopathologic investigations identified a fibrinoid, thrombo-hemorrhagic necrosis affecting small arterioles and capillaries. Later, three categories of the Shwartzman reaction were established, i.e., the generalized Shwartzman phenomenon (a coagulopathic phenomenon which results from two repeated endotoxin injections), the dermal Shwartzman reaction and the single organ or mono-visceral form. Detailed investigations of the Shwartzman phenomena resulted in deeper insight of innate immune sensitization and tolerance, as well as the interplay between clotting and inflammation, thrombosis and fibrinolysis.
NK cells recognize and eliminate pathogen-infected cells without earlier sensitization. Their activation results from various specific receptors that control their differentiation, memory, and exhaustion. NK cells release various cytokines, e.g., IFN-γ and TNF-α/β, and cytoplasmic cytotoxic granules containing e.g., perforin and granulysin, all of which act together to kill pathogen- and host-infected cells. Additionally, NK cells kill other immune cells, e.g., macrophages and dendritic cells, to abolish self-immune reactions. Key mediators of signaling pathways of the cell death processes apoptosis (non-inflammatory and caspase-mediated cell death), necroptosis (pro-inflammatory and non-caspase-mediated), and pyroptosis (inflammasome- and caspase-mediated), together with those of netosis, efferocytosis, and autophagy have been identified recently.