How dying cells alert the immune system to danger

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Abstract
A large number of pathological processes can damage cells in ways that lead to the common end result of cell death. Therefore, when non-physiological cell death occurs in vivo, it indicates that a potentially dangerous situation is developing in a host. The innate immune system has evolved mechanisms to identify potential danger by detecting abnormal cell death. This is accomplished by sensing the release of a subset of molecules (damage-associated molecular patterns, DAMPs) that are normally hidden in living cells or their local environment but are released or exposed when cells die and lose integrity of their plasma membrane. Upon detecting the presence of DAMPs, the innate immune system initiates an acute inflammatory response that rapidly delivers soluble and cellular defences to the site of damage. This response is a double-edged sword that can contain and repair the damage but can also damage normal tissues and in so doing cause disease. DAMPs also stimulate antigen-presenting cells of the innate immune system to migrate to lymphoid tissues and become immunostimulatory for T cells. In this way, the innate immune response alerts the adaptive immune system to potential danger in a manner that helps to initiate responses to any immunogenic antigens at the site of damage. This might have an important role in initiating T-cell responses to tumours, to transplants and in autoimmunity. There has been recent progress in identifying some of what are probably many DAMPs. There remains much to be learned about these molecules, the cells and receptors that sense them, and the pathways they stimulate.