Stress Response And Immunity: Links And Trade Offs

All living organisms face two major challenges: to adjust to constantly changing environment and to protect themselves from pathogens. How organisms integrate responses to these challenges is the subject of this book. Cellular machinery can function properly only in a narrow range of condition. The same is true for multicellular organisms. When conditions deviate from the acceptable range, that creates stress and requires change. Physical stress can be caused by starvation, heat, cold, irradiation, and other factors. In addition, higher animals can experience mental stress caused by fear, neglect, isolation etc. Stress response is a set of measures that preserve homeostasis in the face of environmental changes. Pathogens are another challenge for most life forms. Viruses and mobile genetic elements infect all organisms. Multicellular organisms can also be infected by bacterial and eukaryotic pathogens. These subjects are presented in the first two chapters of the book.

The next section presents the elaborate mechanisms of stress and immune responses in bacteria and archaea. A common response to stress in prokaryotes includes, among other means, switching to an alternative transcriptional mode. Prokaryotic immunodefense mechanisms are built on two strategies that are also conserved in eukaryotes. One is innate immunity based on genetically encoded molecules/receptors. The other — adaptive immunity is based on unique molecules/receptors that are created de novo in response to infection.

Eukaryotic stress response is discussed next. Global inhibition of translation, called integrated stress response, is a common reaction to many stresses in eukaryotic cells. In multicellular organisms, most individual cells have autonomous immunodefense mechanisms which function in collaboration with stress response. Some stress responses can participate in immunodefense. A notable example is unfolded protein response. It cleanses the cell of misfolded proteins plus also targets viral proteins because of their difference from cellular proteins. In animals, cellular stress response can trigger cytokine production and systemic response, which includes inflammation and engagement of specialised immune systems. Even subtle changes in homeostasis can activate such a response. The incredible sensitivity of cellular machinery to changes has a dark side; stress and ensuing immune mechanisms such as inflammation and complement can be induced without infection or substantial injury and lead to pathology.

In complex organisms with specialised immune systems, discussed next, the relationship between stress and immunity becomes more complex and sometimes antagonistic. Mental stress can cause activation of immune mechanisms, which, in turn, can affect the brain’s functioning, and behavior. In the recent decade, science has discovered the paramount importance of interaction of all levels of stress response with immunity in the etiology of many human diseases from atherosclerosis to Alzheimer’s.

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