Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination.
Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination.
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DOI：
10.1186/s12979-020-00210-z
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发表时间：
2020-11-19
期刊：
影响因子：
--
通讯作者：
Blomberg BB
中科院分区：
文献类型：
--
作者：
Frasca D;Blomberg BB
衰老的特点是免疫系统抵抗流感病毒感染和对疫苗接种作出反应的能力逐渐下降。在涉及的几个因素中，除了虚弱和高风险条件的增加外，与年龄相关的细胞和体液免疫反应的减少也起着相关作用。这在很大程度上是由于炎症，老年人的慢性低度炎症状态，与免疫细胞的内在炎症和免疫功能下降有关。衰老通常与流感病毒特异性抗体和流感疫苗特异性抗体反应降低有关，但由于以前的感染或疫苗接种，一些暴露前抗体滴度较高的老年人感染的可能性较小。这种例外的例子是在2009年大流行季节感染的老年人，他们产生的抗体比年轻人产生的抗体具有更广泛的表位识别和更高的亲和力。几项研究已经允许识别B细胞内在缺陷，说明老年人的次优抗体反应。这些缺陷包括：1)类开关重组减少，导致类开关抗体产生二次应答；2)抗体可变区的新生体细胞超突变减少；3)分泌抗体的结合和中和能力以及结合特异性降低；4)与较低抗体应答相关的表观遗传修饰增加；5)炎性B细胞亚群频率增加；6)端粒缩短。虽然流感疫苗接种是预防流感感染的最有效方法，但需要免疫原性更强的疫苗来改善老年人的反应。最近的技术进步使更好地了解免疫细胞中与年龄相关的变化成为可能，这是设计量身定制的疫苗和有效治疗策略所必需的，这些疫苗和策略将能够改善脆弱个体的免疫反应。
Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function. Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure antibody titers, due to a previous infection or vaccination, have less probability to get infected. Examples of this exception are the elderly individuals infected during the 2009 pandemic season who made antibodies with broader epitope recognition and higher avidity than those made by younger individuals. Several studies have allowed the identification of B cell intrinsic defects accounting for sub-optimal antibody responses of elderly individuals. These defects include 1) reduced class switch recombination, responsible for the generation of a secondary response of class switched antibodies, 2) reduced de novo somatic hypermutation of the antibody variable region, 3) reduced binding and neutralization capacity, as well as binding specificity, of the secreted antibodies, 4) increased epigenetic modifications that are associated with lower antibody responses, 5) increased frequencies of inflammatory B cell subsets, and 6) shorter telomeres. Although influenza vaccination represents the most effective way to prevent influenza infection, vaccines with greater immunogenicity are needed to improve the response of elderly individuals. Recent advances in technology have made possible a broad approach to better understand the age-associated changes in immune cells, needed to design tailored vaccines and effective therapeutic strategies that will be able to improve the immune response of vulnerable individuals.
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DOI：
10.4049/jimmunol.1900922
发表时间：
2020-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Avey S;Mohanty S;Chawla DG;Meng H;Bandaranayake T;Ueda I;Zapata HJ;Park K;Blevins TP;Tsang S;Belshe RB;Kaech SM;Shaw AC;Kleinstein SH
通讯作者：
Kleinstein SH
DOI：
10.1084/jem.20171127
发表时间：
2018-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fang D;Cui K;Hu G;Gurram RK;Zhong C;Oler AJ;Yagi R;Zhao M;Sharma S;Liu P;Sun B;Zhao K;Zhu J
通讯作者：
Zhu J
影响因子：
12.7
作者：
Ding, Qiang;Lu, Panpan;Liu, Mei
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Liu, Mei
影响因子：
15.3
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Didierlaurent, Arnaud;Goulding, John;Patel, Seema;Snelgrove, Robert;Low, Lionel;Bebien, Magali;Lawrence, Toby;van Rijt, Leonie S.;Lambrecht, Bart N.;Sirard, Jean-Claude;Hussell, Tracy
通讯作者：
Hussell, Tracy
影响因子：
5.3
作者：
Beli, Eleni;Clinthorne, Jonathan F.;Duriancik, David M.;Hwang, Ilwoong;Kim, Sungjin;Gardner, Elizabeth M.
通讯作者：
Gardner, Elizabeth M.