Stress Response and Immunity: Links and Trade Offs

Stress Response and Immunity: Links and Trade Offs

When environmental conditions deviate from the optimal range, stress ensues. Stress response is a set of reactions that allow the organism to adjust and survive adverse conditions. Stress can be ...
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Stress Response Meets Autonomous Immunity

Pp. 307-338 (32)

Nadia Danilova

Abstract

Stress response contributes to autonomous immune responses. Many stresses including infection induce integrated stress response (ISR). ISR is mediated by a set of kinases PKR, PERK, HRI, and GCN2. Viral dsRNA activates PKR. Viral proteins are produced in the endoplasmic reticulum and may cause ER stress, which activates PERK. Infection also can cause iron deficiency sensed by HRI kinase and amino acid shortage sensed by GCN2. The arrest of translation caused by ISR inhibits viral replication and activates NFkB, a major regulator of immunity. Therefore, ISR acts as an immunodefense mechanism. Other stress responses that contribute to immune defense include unfolded protein response (UPR). UPR activates degradation of ERassociated mRNAs and proteins including viral ones. DNA damage response leads to NFkB activation, and so does oxidative stress through various mechanisms. The major stress response factor p53 has anti-viral activity. Autophagy activated by many stresses also plays a role in immunodefense by degrading intracellular pathogens.

Keywords:

DNA damage response, ERAD, Homeostasis, Immune response, Integrated stress response, NLRP3 inflammasome, Nrf2, Oxidative stress, RIDD, Unfolded protein response, Xenophagy.

Affiliation:

Department of Molecular Cell & Developmental Biology, University of California, Los Angeles CA, USA.