Innate and adaptive immune responses to cell death

Abstract

Summary The immune system plays an essential role in protecting the host against infections and to accomplish this task has evolved mechanisms to recognize microbes and destroy them. In addition, it monitors the health of cells and responds to ones that have been injured and die, even if this occurs under sterile conditions. This process is initiated when dying cells expose intracellular molecules that can be recognized by cells of the innate immune system. As a consequence of this recognition, dendritic cells are activated in ways that help to promote T-cell responses to antigens associated with the dying cells. In addition, macrophages are stimulated to produce the cytokine interleukin-1 that then acts on radioresistant parenchymal cells in the host in ways that drive a robust inflammatory response. In addition to dead cells, a number of other sterile particles and altered physiological states can similarly stimulate an inflammatory response and do so through common pathways involving the inflammasome and interleukin-1. These pathways underlie the pathogenesis of a number of diseases.

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

“…Local sterile inflammation after tissue injury and necrotic cell death has an important role in tissue repair (Rock et al, 2011), whereas systemic sterile inflammation or the cytokine storm triggered after major trauma can be lethal (Schneider et al, 2011). Recently, it has been reported that psychological and/or acute intense stressor exposure in the absence of overt tissue damage can evoke a detectable local and systemic sterile inflammatory response and that DAMPs may have a (Fleshner, 2013;Frank et al, 2015b;Maslanik et al, 2013;Miller et al, 2015).…”

The melatonin immunomodulatory actions in radiotherapy

“…Cell death mechanisms that occur after irradiation include mitotic catastrophe, necrosis, apoptosis, autophagy, and senescence (Golden et al 2012). The response of immune cells to these cell death pathways leads to the production of cytokines that stimulate various signaling pathways in normal tissues (Rock et al 2011;Muralidharan and Mandrekar 2013). Immunogenic cell death pathways include necrosis and necroptotic.…”

“…Effects of radiation exposure are mediated by radiation-induced damage to DNA, organelles, and membranes. Intense damages after exposure to radiation stimulate immune responses that result in subsequent consequences (Rock et al 2011;Muralidharan and Mandrekar 2013).…”

Sustained tumour eradication after induced caspase-3 activation and synchronous tumour apoptosis requires an intact host immune response

“…Thus, apoptosis is considered to be immunologically ignored or functions to suppress immune activation via the induction of tolerance, with apoptotic bodies rapidly cleared by phagocytes. 1 In contrast, necrotic cell death is associated with loss of plasma membrane integrity, facilitating release of danger signals 2 or damage-associated molecular patterns 3 (DAMPs) including uric acid, 4 heat shock proteins (HSPs) 5 and mitochondrial constituents 6 that serve as endogenous immune adjuvants. DAMPs released from dying cells can stimulate an effective immune response against cellular antigen, in much the same way as pathogenic signals arising from infection.…”