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 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 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 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-associated inflammation alters the aging trajectory

2019 ◽  
Vol 41 (1) ◽  
pp. 22-25
Author(s):  
Grace Teskey ◽  
Cedoljub Bundalovic-Torma ◽  
Dawn Bowdish
Keyword(s):  
Immune System ◽  
Aging Process ◽  
Jonathan Swift ◽  
The Other ◽  
Long Life ◽  
Cognitively Intact

Jonathan Swift said, ‘Every man desires to live long, but no man wishes to be old’. Most of us have ambivalent feelings about aging. We may want a long life, but those extra years hold less appeal if we are too ill to enjoy them. At one extreme of the aging trajectory are those who become frail, immobile and dependent in their 5th or 6th decade. At the other extreme are those who live to 100 or beyond remaining cognitively intact, active and engaged in their communities. We wonder what causes underlie this diversity in the aging process? Why do some of us age well and others poorly? The immune system plays a central role in health in our later years.

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 Effects of carotenoids on human immune function

1999 ◽  
Vol 58 (3) ◽  
pp. 713-718 ◽  
Author(s):  
David A. Hughes
Keyword(s):  
Immune Function ◽  
Cell Function ◽  
Immune Cell ◽  
Antioxidant Properties ◽  
The Elderly ◽  
Causative Factor ◽  
Epidemiological Studies ◽  
Wide Range ◽  
Β Carotene

Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, β-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that β-carotene may enhance immune cell function. Several human trials, using dietary β-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of β-carotene supplementation on lung cancer risk will be discussed.

scholarly journals Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Thitinee Vanichapol ◽  
Somchai Chutipongtanate ◽  
Usanarat Anurathapan ◽  
Suradej Hongeng
Keyword(s):  
Immune System ◽  
T Cell ◽  
Cell Therapy ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Escape ◽  
Adoptive Cell Therapy ◽  
Immune Recognition ◽  
T Cell Therapy ◽  
Cell Therapies

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function. Several subtypes of immune cells that infiltrate tumors can foster tumor development, harbor immunosuppressive activity, and decrease an efficacy of adoptive cell therapies. Therefore, an understanding of the dual role of the immune system under the influences of the TME has been crucial for the development of effective therapeutic strategies against solid cancers. This review aims to depict key immune players and cellular pathways involved in the dynamic interplay between the TME and the immune system and also to address challenges and prospective development of adoptive T cell transfer for neuroblastoma.

scholarly journals Molecular Mechanisms of Leukocyte Migration and Its Potential Targeting—Lessons Learned From MKL1/SRF-Related Primary Immunodeficiency Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Evelien G. G. Sprenkeler ◽  
Carla Guenther ◽  
Imrul Faisal ◽  
Taco W. Kuijpers ◽  
Susanna C. Fagerholm
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Serum Response Factor ◽  
Cell Function ◽  
Immune Cell ◽  
Leukocyte Adhesion ◽  
Adaptive Immune System ◽  
Lessons Learned ◽  
Megakaryoblastic Leukemia

Megakaryoblastic leukemia 1 (MKL1) deficiency is one of the most recently discovered primary immunodeficiencies (PIDs) caused by cytoskeletal abnormalities. These immunological “actinopathies” primarily affect hematopoietic cells, resulting in defects in both the innate immune system (phagocyte defects) and adaptive immune system (T-cell and B-cell defects). MKL1 is a transcriptional coactivator that operates together with serum response factor (SRF) to regulate gene transcription. The MKL/SRF pathway has been originally described to have important functions in actin regulation in cells. Recent results indicate that MKL1 also has very important roles in immune cells, and that MKL1 deficiency results in an immunodeficiency affecting the migration and function of primarily myeloid cells such as neutrophils. Interestingly, several actinopathies are caused by mutations in genes which are recognized MKL(1/2)-dependent SRF-target genes, namely ACTB, WIPF1, WDR1, and MSN. Here we summarize these and related (ARPC1B) actinopathies and their effects on immune cell function, especially focusing on their effects on leukocyte adhesion and migration. Furthermore, we summarize recent therapeutic efforts targeting the MKL/SRF pathway in disease.

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