PMC:7148425 / 4902-7058 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7148425","sourcedb":"PMC","sourceid":"7148425","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7148425","text":"Immunosenescence and its underlying mechanisms\nAltered immune competence with increasing age, so-called immunosenescence [6], is the result of changes at multiple levels of the immune system over time. It includes the altered balance of immune cell production in the bone marrow resulting in reduced lymphopoiesis and increased output of myeloid lineage cells which are also functionally compromised. Thymic involution substantially reduces the output of naïve T cells and the TCR repertoire contracts over time. Although loss of circulating naïve B cells is less profound than naïve T cells, reduced BCR repertoire diversity with age is also well recognized. Furthermore, aging is associated with the dysfunction of innate immune cells like neutrophils at sites of infection possibly due to the poorer capacity of the adaptive immune system to reign in over-exuberant inflammatory responses. The ability to generate adaptive immune responses is compromised by dysfunction of antigen-presenting cells and disorganised and fibrotic lymph node architecture. Collectively, these changes prevent appropriate control of the initial inflammatory response and decrease the generation of an efficient and robust adaptive immune response which requires the production of large number of functional effector T cells and B cells. For all these reasons, protective responses to infection or vaccination tend to be on average lower in many older adults than in the young, but there is enormous inter-individual variation in people owing to the individual variations of genetics and the history of environmental exposures. Hence, two crucial questions are raised by these considerations: 1) how can we measure immune and physiological status in an individual in a clinically meaningful manner and 2) how can we intervene at the crucial checkpoints thus identified in order to restore appropriate immune function? Identification of biomarkers of protective or detrimental responses to a SARS-CoV-2 infection or vaccine and determination of the kinetic pattern of these biomarkers during the course of infection or vaccine response are critical to address these 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