age-associated changes in immunity; immunosenescence
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Introduction
Changes in immunity with age include changes in cellular immunity, humoral immunity & innate immunity.
Pathology
- defective immune response
- increased risk of infection
- tendency for latent disease to reactivate
- increased susceptibility to neoplasm
- increased risk of autoimmune diseases
- poor responses to vaccination
- reduced immume surveillance
- maladaptive repair after injury
- maladaptive inflammatory response
- increased systemic inflammation
- increased risk & accelerated progression of age-related diseases
Changes in T-cells with aging
- decreases
- virgin or reactive T-cells
- mitogen-responsive T-cells
- stem cell generation of T-cells
- proliferative response
- expression of early activation genes
- sensitivity to activating signals
- cytotoxic cell target binding
- supressor cell function
- generation of cytotoxic T-cells
- T-helper cell facilitated antibody production
- increases
- memory T-cells
- T-cell facilitated autoantibody production
- NK cell number increase, but function declines
- shift from Th-1 to Th-2 response
Changes in B-cells with aging
- decreases
- surface MHC class II molecule expression
- pool of B-cells with proliferative potential
- bone marrow B-cell precursors
- T-cell dependent antibody-forming B-cells
- antibody production to primary & secondary antigens
- specificity & binding affinity of antibodies
- antigen reconigition
- autoantibodies common: increases in anti-idiotype antibodies
Changes in cytokines with aging
- increased basal secretion of IFN-gamma[6]
- increased basal & stimulated PGE2[6]
- increased release of TGF-beta
- increased release of TNF
- inflammatory marker cytokine CXCL9 upregulates multiple genes implicated in inflammation & is involved in immunosenescence, vascular aging & adverse cardiac remodeling[8]
Changes in interleukins with aging
- decreases
- monocyte secretion of IL1
- IL2 mRNA
- proportion of cells expressing IL2 receptor
- high-affinity binding sites for IL2
- T-cell secretion of IL2
- T-cell proliferative response to IL2
- IL2 stimulated NK production of IFN
- memory T-cell secretion of IL4
- non-specific stimulation of IL8 secretion
- IL12 production in TB-infected mouse lungs
- increases
- increased release of IL1
- lymphocyte production of IL1 in mixed lymphocyte culture
- memory T-cell production of IL2
- non-specific stimulation of T-cell IL4 & IL6
- lymphocyte production of IL5
- lymphocyte production of IL10
- increased release of IL1
Physiology
- involution of thymus
- changes in innate immunity
- diminished protective effect of skin & mucous membranes
- decreased cell-mediated immunity
- decreased delayed hypersensitivity
- deceased proliferative response to mitogens
- decreased number of T-cells
- increased number of T-suppressor cells (CD8+)
- decreased number of T-helper cells (CD4+) (decreased IL-2)
- fewer naive & more memory T-cells[6]
- increase in pro-inflammatory T-cells (CD28-)
- changes in humoral immunity
- decreased production of B-cells by bone marrow
- decreased antibody titers
- lower affinity antibodies
- increased autoantibodies
- anti-idiotype antibodies
- increased risk of MGUS
- more non-responders of vaccinations
- decreased primary & secondary immune responses[6]
- impaired macrophage function - loss of phagocytosis activity
- changes in release of cytokines
- loss of proliferative capacity of hematopoietic stem cells[6]
- inability to upregulate macrophage production
- inability to upregulate neutrophil production
- skin breakdown
More general terms
Additional terms
References
- ↑ Essentials of Clinical Geriatrics, 4th ed, Kane RL et al (eds) McGraw Hill, NY, 1999
- ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ The Merck Manual of Geriatrics, 3rdh ed, Merck & Co, Rahway NJ, 2000
- ↑ Taffet GE, Physiology of Aging, In: Geriatric Medicine: An Evidence-Based Approach, 4th ed, Cassel CK et al (eds), Springer-Verlag, New York, 2003
- ↑ Burns EA & Goodwin JS, Immunology of Aging In: Geriatric Medicine: An Evidence-Based Approach, 4th ed, Cassel CK et al (eds), Springer-Verlag, New York, 2003
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - ↑ Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009 Nov;22(11):1041-50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19624493
- ↑ 8.0 8.1 Buck Institute for Research on Aging 'Clock' created to predict immunological health and chronic diseases of aging Research highlights the critical role of the immune system in the aging process. Science Daily. Science News. July 12, 2021 https://www.sciencedaily.com/releases/2021/07/210712122159.htm
Sayed N, Huang Y, Nguyen K et al An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nature Aging 2021 Not indexed in PubMed https://www.nature.com/articles/s43587-021-00082-y - ↑ Aw D, Silva AB, Palmer DB Immunosenescence: emerging challenges for an ageing population. Immunology. 2007 Apr;120(4):435-46. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17313487 PMCID: PMC2265901 Free PMC article
- ↑ Margolick JB, Leng SX Johns Hopkins. Geriatric Medicine & Gerontology Immune Senescence https://www.hopkinsmedicine.org/geriatric_medicine_gerontology/aging_research/biology_healthy_aging/immune_senescence.html
- ↑ Frasca D, Diaz A, Romero M etl al B Cell Immunosenescence. Annu Rev Cell Dev Biol. 2020 Oct 6;36:551-574 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33021823 Free PMC article. https://www.annualreviews.org/doi/abs/10.1146/annurev-cellbio-011620-034148
- ↑ Thio HB Aging immune system (immunosenescence) and the skin Webinar on Cosmetology and Trichology, September 04, 2020 J Ageing & Geriatr Med. 2020. Sept 4. https://www.scitechnol.com/peer-review/aging-immune-system-immunosenescence-and-the-skin-GRAf.pdf
- ↑ Crooke SN, Ovsyannikova IG, Poland GA, Kennedy RB Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses. Exp Gerontol. 2019 Sep;124:110632 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31201918 PMCID: PMC6849399 Free PMC article