Host Resistance and Immune Aging

Abstract

Human immune system aging results in impaired responses to pathogens or vaccines. In the innate immune system, which mediates the earliest pro-inflammatory responses to immunologic challenge, processes ranging from Toll-like Receptor function to Neutrophil Extracellular Trap formation are generally diminished in older adults. Dysregulated, enhanced basal inflammation with age reflecting activation by endogenous damage-associated ligands contributes to impaired innate immune responses. In the adaptive immune system, T and B cell subsets and function alter with age. The control of cytomegalovirus infection, particularly in the T lineage, plays a dominant role in the differentiation and diversity of the T cell compartment.

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…29,34,37 This finding in addition to developmental and signaling alterations alongside with age-related decrease in T-cell generation are all found in cells from older adults, which contribute to functional deficits. The altered signaling is fostered by the persistence of low quantity of pro-inflammatory cytokines and increased production of ROS, both characteristics of InflammAging.…”

“…Thymus starts to involute during childhood and continues to involute in adults (at a rate of approximately 1-3% per year) 29 ; for this reason thymus-dependent T-cell creation declines with aging reducing the number of naive T-cells. Under physiologic conditions, thymus releases immature lymphocytes termed "recent thymic emigrants" (RTEs) which maintain a stable pool of na€ ıve T-cells.…”

“…30 Whether thymus activity is maintained in adulthood is debated but it is accepted that most (approximately 90% of CD4C T cells) of T cells in older adults are generated from division of cells in the existing T-lymphocyte pool (as RTEs). 29,31,32 Consequently, in older adults, most T-cells appear to be antigen-experienced memory T-cells. 29,31,32 In thymectomized young adults this pattern was strongly associated with seropositivity to CMV.…”

“…29,31,32 Consequently, in older adults, most T-cells appear to be antigen-experienced memory T-cells. 29,31,32 In thymectomized young adults this pattern was strongly associated with seropositivity to CMV. 33 Kohler et al showed that the surface molecule CD31 (PECAM-1) can be used to discriminate between CD31C thymic naive and CD31¡ central naive CD4C T-cells in the peripheral blood of healthy humans.…”

“…26,34 CD28C has a central role in the proliferation of CD8C T-cells as one of the main co-stimulator of TC cell response during the antigen presentation between APCs and T-cells (in conjunction with TCR recognition by peptide bound to host MHC proteins on APCs). 26,29,38 In addition to the loss of CD28, CD8 T-cells express other markers of exhaustion, replicative senescence (mediated by upregulation of p21 and p16, as explained above), or terminal differentiation in the context of aging (such as PD-1, CD57, or KLRG1); moreover, they have increased production of IL6 and TNF-a 28 and reduced length of telomerases. 8,28,29,38 Recent studies have reported that the senescence phenotype in both CD8 effector memory and CD4 T-cells is strongly associated with irregular signaling via the p38 MAP kinase.…”