scholarly journals Immunosenescence and human vaccine immune responses

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Stephen N. Crooke ◽  
Inna G. Ovsyannikova ◽  
Gregory A. Poland ◽  
Richard B. Kennedy
Keyword(s):  
Older Adults ◽  
Immune System ◽  
Clinical Outcomes ◽  
B Lymphocyte ◽  
Cell Function ◽  
Immune Cell ◽  
Vaccine Development ◽  
Older Individuals ◽  
Functional Changes ◽  
Age Related

Abstract The age-related dysregulation and decline of the immune system—collectively termed “immunosenescence”—has been generally associated with an increased susceptibility to infectious pathogens and poor vaccine responses in older adults. While numerous studies have reported on the clinical outcomes of infected or vaccinated individuals, our understanding of the mechanisms governing the onset of immunosenescence and its effects on adaptive immunity remains incomplete. Age-dependent differences in T and B lymphocyte populations and functions have been well-defined, yet studies that demonstrate direct associations between immune cell function and clinical outcomes in older individuals are lacking. Despite these knowledge gaps, research has progressed in the development of vaccine and adjuvant formulations tailored for older adults in order to boost protective immunity and overcome immunosenescence. In this review, we will discuss the development of vaccines for older adults in light of our current understanding—or lack thereof—of the aging immune system. We highlight the functional changes that are known to occur in the adaptive immune system with age, followed by a discussion of current, clinically relevant pathogens that disproportionately affect older adults and are the central focus of vaccine research efforts for the aging population. We conclude with an outlook on personalized vaccine development for older adults and areas in need of further study in order to improve our fundamental understanding of adaptive immunosenescence.

scholarly journals Dysregulation of Systemic Immunity in Aging and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Jenny Lutshumba ◽  
Barbara S. Nikolajczyk ◽  
Adam D. Bachstetter
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Human Subjects ◽  
Brain Inflammation ◽  
Adaptive Immune Cells ◽  
Age Related ◽  
The Brain ◽  
Age Related Changes

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks coupled with more traditional immune system stimuli like infection or injury likely combine to trigger and maintain persistent microglial and thus brain inflammation. This review summarizes age-related changes in immune cell function, with special emphasis on lymphocytes as a source of inflammation, and discusses how such changes may potentiate both systemic and central nervous system inflammation to culminate in dementia. We recap the understudied area of AD-associated changes in systemic lymphocytes in greater detail to provide a unifying perspective of inflammation-fueled dementia, with an eye toward evidence of two-way communication between the brain parenchyma and blood immune cells. We focused our review on human subjects studies, adding key data from animal models as relevant.

scholarly journals Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics

2021 ◽  
Author(s):  
Ozlem Bulut ◽  
Gizem Kilic ◽  
Jorge Domínguez-Andrés
Keyword(s):  
Immune System ◽  
Aging Process ◽  
Cell Function ◽  
Immune Cell ◽  
Immunological Memory ◽  
Metabolic Reprogramming ◽  
The Other ◽  
Immune Memory ◽  
Age Related ◽  
Wide Range

AbstractNon-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies.

scholarly journals Cellular and metabolic mechanisms of nutrient actions in immune function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Newsholme
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Vitamin D ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Structure ◽  
Nutritional Intervention ◽  
Immune Cell Function ◽  
And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

Supplementation with Selenium Restores Age-Related Decline in Immune Cell Function

1995 ◽  
Vol 209 (4) ◽  
pp. 369-375 ◽  
Author(s):  
M. Roy ◽  
L. Kiremidjian-Schumacher ◽  
H. I. Wishe ◽  
M. W. Cohen ◽  
G. Stotzky
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Age Related

scholarly journals AGE-BASED STEREOTYPE THREAT: A SYSTEMATIC REVIEW OF PRIMING TECHNIQUES AND THEIR EFFECTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S455-S456
Author(s):  
Francesco Vailati Riboni ◽  
Francesco Pagnini
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Stereotype Threat ◽  
Functional Performance ◽  
Later Life ◽  
Experimental Methods ◽  
Experimental Manipulation ◽  
Older Individuals ◽  
Negative Stereotypes ◽  
Age Related

Abstract Age-based stereotype threat (ABST) occurs when older adults are influenced by negative stereotypes about age-related decline and functional losses and ironically behave in disengaging and self-defeating ways that confirm the stereotype (Steele & Aronson, 1995). Aging stereotypes are found to be strong predictors of health and illness outcomes in later life, and are associated with performance in specific areas, mainly in cognitive and physical domains. The current study reviewed the experimental methods and their reported effects previously published in the literature to determine if there were different ABST methods were associated with different types of age-related outcomes. We conducted a systematic review, screening the scientific literature for papers that included experimental manipulation of age-related stereotypes as an independent variable, focusing on samples of older adults (1113 articles, most published after 2003). Through a classification of the common and distinctive characteristics of the different stereotype manipulation techniques, we were able to identify three specific types of experimental methods: by instruction, tests, and interpersonal exposure. Although the mechanism by which stereotypes are associated with functional outcomes in older adults remains unclear, our review suggests it is possible to experimentally control the activation of the stereotype by manipulating its specific characteristics and the way older participants are exposed to it. Findings also highlight the possibility that specific experimental methods used to induce ABST in older individuals may lead to unique and different consequences on functional performance variation.

scholarly journals Reduction of leucocyte cell surface disulfide bonds during immune activation is dynamic as revealed by a quantitative proteomics workflow (SH-IQ)

Open Biology ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 180079
Author(s):  
Monika Stegmann ◽  
A. Neil Barclay ◽  
Clive Metcalfe
Keyword(s):  
Immune System ◽  
Cell Surface ◽  
Immune Activation ◽  
Disulfide Bonds ◽  
Cell Function ◽  
Immune Cell ◽  
Surface Proteins ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Pathogen Clearance

Communication through cell surface receptors is crucial for maintaining immune homeostasis, coordinating the immune response and pathogen clearance. This is dependent on the interaction of cell surface receptors with their ligands and requires functionally active conformational states. Thus, immune cell function can be controlled by modulating the structure of either the receptor or the ligand. Reductive cleavage of labile disulfide bonds can mediate such an allosteric change, resulting in modulation of the immune system by a hitherto little studied mechanism. Identifying proteins with labile disulfide bonds and determining the extent of reduction is crucial in elucidating the functional result of reduction. We describe a mass spectrometry-based method—thiol identification and quantitation (SH-IQ)—to identify, quantify and monitor such reduction of labile disulfide bonds in primary cells during immune activation. These results provide the first insight into the extent and dynamics of labile disulfide bond reduction in leucocyte cell surface proteins upon immune activation. We show that this process is thiol oxidoreductase-dependent and mainly affects activatory (e.g. CD132, SLAMF1) and adhesion (CD44, ICAM1) molecules, suggesting a mechanism to prevent over-activation of the immune system and excessive accumulation of leucocytes at sites of inflammation.

EZH2 function in immune cell development

2020 ◽  
Vol 401 (8) ◽  
pp. 933-943 ◽  
Author(s):  
Stephen L. Nutt ◽  
Christine Keenan ◽  
Michaël Chopin ◽  
Rhys S. Allan
Keyword(s):  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Proliferating Cells ◽  
Hematopoietic Stem ◽  
Polycomb Repressive Complex 2 ◽  
Current State ◽  
Core Components ◽  
And Function ◽  
Cell Cycle Inhibitors

AbstractThe polycomb repressive complex 2 (PRC2) consists of three core components EZH2, SUZ12 and EED. EZH2 catalyzes the methylation of lysine 27 of histone H3, a modification associated with gene silencing. Through gene duplication higher vertebrate genomes also encode a second partially redundant methyltransferase, EZH1. Within the mammalian immune system most research has concentrated on EZH2 which is expressed predominantly in proliferating cells. EZH2 and other PRC2 components are required for hematopoietic stem cell function and lymphocyte development, at least in part by repressing cell cycle inhibitors. At later stages of immune cell differentiation, EZH2 plays essential roles in humoral and cell-mediated adaptive immunity, as well as the maintenance of immune homeostasis. EZH2 is often overactive in cancers, through both gain-of-function mutations and over-expression, an observation that has led to the development and clinical testing of specific EZH2 inhibitors. Such inhibitors may also be of use in inflammatory and autoimmune settings, as EZH2 inhibition dampens the immune response. Here, we will review the current state of understanding of the roles for EZH2, and PRC2 more generally, in the development and function of the immune system.

scholarly journals Automated Speech Recognition Systems and Older Adults: A Literature Review and Synthesis

2019 ◽  
Vol 63 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Lauren Werner ◽  
Gaojian Huang ◽  
Brandon J. Pitts
Keyword(s):  
Older Adults ◽  
Speech Recognition ◽  
Current Knowledge ◽  
Age Groups ◽  
Older Individuals ◽  
Age Related ◽  
Wide Range ◽  
Automated Speech Recognition ◽  
Technological Developments ◽  
Physical Changes

The number of older adults is growing significantly worldwide. At the same time, technological developments are rapidly evolving, and older populations are expected to interact more frequently with such sophisticated systems. Automated speech recognition (ASR) systems is an example of one technology that is increasingly present in daily life. However, age-related physical changes may alter speech production and limit the effectiveness of ASR systems for older individuals. The goal of this paper was to summarize the current knowledge on ASR systems and older adults. The PRISMA method was employed and 17 studies were compared on the basis of word error rate (WER). Overall, WER was found to be influenced by age, gender, and the number of speech samples used to train ASR systems. This work has implications for the development of future human-machine technologies that will be used by a wide range of age groups.

Aging and immune response to exercise

1998 ◽  
Vol 76 (5) ◽  
pp. 562-572 ◽  
Author(s):  
Shoji Shinkai ◽  
Masamitsu Konishi ◽  
Roy J Shephard
Keyword(s):  
Cellular Immunity ◽  
Acute Exercise ◽  
Cell Function ◽  
Nk Cell ◽  
Cell Activity ◽  
The Elderly ◽  
Strenuous Exercise ◽  
Elderly Subjects ◽  
Older Individuals ◽  
Age Related

Human immune function undergoes adverse changes with aging. The T cells, which have a central role in cellular immunity, show the largest age-related differences in distribution and function, with thymus involution as the apparent underlying cause. The immune responses to acute exercise and training have not been studied extensively in the elderly. The natural killer (NK) cell response to a single exercise challenge is normal in older individuals, but immediately after exercise the elderly subjects manifest less suppression of phytohemagglutinin (PHA)-induced lymphocyte proliferation than younger individuals. In contrast, a strenuous exercise seems to induce a more sustained postexercise suppression of cellular immunity in older individuals than in their young peers. A few cross-sectional comparisons of immune status between physically fit elderly individuals and young sedentary controls suggest that habitual physical activity may enhance NK cell activity, checking certain aspects of the age-related decline in T cell function, such as reduced mitogenesis in response to plant lectins and decreases in the production of certain types of cytokine. The clinical implications, however, remain to be clarified by future study.Key words: immune senescence, innate immunity, adaptive immunity.

Conclusion

2016 ◽  
Author(s):  
Maria A. Sullivan
Keyword(s):  
Older Adults ◽  
Substance Use ◽  
The Elderly ◽  
Social Consequences ◽  
Individual Therapy ◽  
Older Individuals ◽  
Prescribing Practices ◽  
Elderly Age ◽  
Age Related ◽  
The Impact

Addiction in older adults very often goes unrecognized, for several reasons: social biases about the elderly, age-related metabolic changes, and the inappropriate use of prescription benzodiazepines and opioids to address untreated anxiety and mood conditions. Alcohol or substance-use disorders (SUDs) in older individuals may present in subtle and atypical ways. Strategies to overcome such difficulties include systematic screening using validated instruments, patient education regarding the impact of psychoactive substances on health, and cautious prescribing practices. Relying on standard DSM criteria may result in a failure to detect an SUD that presents with cognitive symptoms or physical injury, as well as the absence of work or social consequences. Older individuals can benefit from the application of risk-stratification measures, and they can be referred, e.g., to age-appropriate group therapy and non-confrontational individual therapy focusing on late-life issues of loss and sources of social support, as well as be offered medication management for alcohol or substance use disorder. Although research has been limited in this population, treatment outcomes have been found to be superior in older adults than younger adults.

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