Aging-induced fragility of the immune system

Jones, Eric; Sheng, Jiming; Carlson, Jean M.; Wang, Shenshen

doi:10.1016/j.jtbi.2020.110473

Cited by 10 publications

(8 citation statements)

References 60 publications

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“…The immune system arms living organisms through cells acting as distributed military troops allocated at specific openings throughout the body . It ensures the immune modulation, homeostasis, and surveillance by the “chief guarders”, consisting of phagocytes and granulocytes and the complementary system as a first line of defense .…”

Section: Nanotechnology Derived Immunotherapymentioning

confidence: 99%

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

et al. 2021

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Immunotherapy has revolutionized the modality for establishing a firm immune response and immunological memory. However, intrinsic limitations of conventional low responsive poor T cell infiltration and immune related adverse effects urge the coupling of cancer nanomedicines with immunotherapy for boosting antitumor response under ultrasound (US) sensitization to mimic dose-limiting toxicities for safe and effective therapy against advanced cancer. US is composed of high-frequency sound waves that mediate targeted spatiotemporal control over release and internalization of the drug. The unconventional US triggered immunogenic nanoengineered arena assists the limited immunogenic dose, limiting toxicities and efficacies. In this Review, we discuss current prospects of enhanced immunotherapy using nanomedicine under US. We highlight how nanotechnology designs and incorporates nanomedicines for the reprogramming of systematic immunity in the tumor microenvironment. We also emphasize the mechanical and biological potential of US, encompassing sonosensitizer activation for enhanced immunotherapeutic efficacies. Finally, the smartly converging combinational platform of US stimulated cancer nanomedicines for amending immunotherapy is summarized. This Review will widen scientists' ability to explore and understand the limiting factors for combating cancer in a precisely customized way.

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Section: Nanotechnology Derived Immunotherapymentioning

confidence: 99%

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

et al. 2021

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“…Advanced age increases the risk of autoimmunity. Autoantibody formation increases in old individuals (40).…”

Section: Immune Systemmentioning

confidence: 99%

Aging and geriatric palliative care

Saricam¹,

Kahveci

2021

Anatolian Current Medical Journal

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“…Our work is complementary to most of the modeling efforts in the field. Statistical models of immune systems have explored how resource costs and evolutionary constraints influence immune responses to diverse and evolving pathogens [21][22][23][24][25][26][27][28][29][30][31]. From a complementary perspective, we will demonstrate that active forces and physical constraints can be harnessed to promote the emergence of phenotypic plasticity.…”

Section: Introductionmentioning

confidence: 99%

Molecular tug of war reveals adaptive potential of an immune cell repertoire

Jiang¹,

Wang²

2022

Preprint

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The adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B lymphocytes expressing high-affinity antigen receptors. However, this Darwinian process inside an individual appears ineffective, hitting a modest ceiling of antigen-binding affinity. Experiment began to reveal that evolving B cells physically extract antigens from presenting cells and that the extraction level dictates clonal expansion; this challenges the prevailing assumption that the equilibrium constant of receptor-antigen binding determines selective advantage. We present a theoretical framework to explore whether, and how, such tug-of-war antigen extraction impacts the quality and diversity of an evolved B cell repertoire. We find that the apparent ineffectiveness of clonal selection can be a direct consequence of the non-equilibrium nature of antigen recognition. Our theory predicts that the physical strength of antigen tethering under tugging forces sets the affinity ceiling. Meanwhile, the model showed that, intriguingly, cells can use force variability to diversify binding phenotype without compromising fitness, thus remaining plastic under resource constraint. These results suggest that active probing of receptor quality via a molecular tug of war during antigen recognition limit the potency of response to the current antigen, but confer adaptive benefit for protection against future variants. Importantly, a saddle point in the fitness landscape of B cell-phenotype evolution emerges from the tug-of-war setting, which rationalizes multiple key phenomenology and puts forward a role of active physical dynamics in immune adaptation.

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Aging-induced fragility of the immune system

Cited by 10 publications

References 60 publications

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

Aging and geriatric palliative care

Molecular tug of war reveals adaptive potential of an immune cell repertoire

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