Advances in Immune Characteristics and Immune Regulation in the Elderly

doi:10.12114/j.issn.1007-9572.2020.00.373

Abstract

Abstract: Distinctive physiological changes occur with aging in immune system and other human body systems.How to determine therapies to effectively boost the weakened immune system in the elderly，is a major medical challenge of the 21st century.Probiotics and thymosin，two immunity-modulators，have obtained increasing attention in terms of benefiting the immune system in the elderly.Here we reviewed the role of immunity，immune characteristics of the elderly，recent advances in immunomodulators，problems existing in current studies on immunosenescence，and the application prospect of probiotics combined with thymosin in modulating immunity in the elderly，with a view to providing clinical and theoretical basis for promoting the health of the elderly.

Key words: Immunity, Immunomodulation, Aging, Probiotics, Thymosin

摘要： 随着年龄的增长，人体生理机能发生特征性改变，老年人的免疫功能有所减弱，制定平衡老年人免疫缺陷的战略是21世纪医学的一大挑战。其中益生菌和胸腺肽对于老年人的有益作用越来越受到重视。本文综述了免疫的作用、老年人免疫系统的特点以及免疫调节剂的研究进展，阐述了免疫衰老现况研究中存在的一些问题及益生菌联合胸腺肽在老年人免疫中的应用前景，为促进老年人健康提供临床理论依据。

关键词: 免疫, 免疫调节, 衰老, 益生菌, 胸腺肽

WANG Jian,GONG Yanfeng. Advances in Immune Characteristics and Immune Regulation in the Elderly　[J]. Chinese General Practice, 2021, 24(11): 1431-1435. DOI: 10.12114/j.issn.1007-9572.2020.00.373.
王健,龚燕锋. 老年人免疫特点及免疫调节的研究进展[J]. 中国全科医学, 2021, 24(11): 1431-1435. DOI: 10.12114/j.issn.1007-9572.2020.00.373.

References

［1］QUINN K M，FOX A，HARLAND K L，et al．Age-related decline in primary CD8+ T cell responses is associated with the development of senescence in virtual memory CD8+ T cells［J］．Cell Rep，2018，23（12）：3512-3524．DOI：10.1016/j.celrep.2018.05.057.
［2］ESENSTEN J H，HELOU Y A，CHOPRA G，et al．CD28 costimulation：from mechanism to therapy［J］．Immunity，2016，44（5）：973-988．DOI：10.1016/j.immuni.2016.04.020.
［3］NIELSEN C M，WHITE M J，GOODIER M R，et al．Functional significance of CD57 expression on human NK cells and relevance to disease［J］．Front Immunol，2013，4：422．DOI：10.3389/fimmu.2013.00422.
［4］ENANI S，PRZEMSKA-KOSICKA A，CHILDS C E，et al．Impact of ageing and a synbiotic on the immune response to seasonal influenza vaccination；a randomised controlled trial［J］．Clin Nutr，2018，37（2）：443-451．DOI：10.1016/j.clnu.2017.01.011.
［5］ONYEMA O O，NJEMINI R，FORTI L N，et al．Aging-associated subpopulations of human CD8+ T-lymphocytes identified by their CD28 and CD57 phenotypes［J］．Arch Gerontol Geriatr，2015，61（3）：494-502．DOI：10.1016/j.archger.2015.08.007.
［6］ONYEMA O O，DECOSTER L，NJEMINI R，et al．Shifts in subsets of CD8+ T-cells as evidence of immunosenescence in patients with cancers affecting the lungs：an observational case-control study［J］．BMC Cancer，2015，15：1016．DOI：10.1186/s12885-015-2013-3.
［7］HASSOUNEH F，CAMPOS C，LóPEZ-SEJAS N，et al．Effect of age and latent CMV infection on CD8+?CD56+ T cells （NKT-like） frequency and functionality［J］．Mech Ageing Dev，2016，158：38-45．DOI：10.1016/j.mad.2015.12.003.
［8］DI BENEDETTO S，DERHOVANESSIAN E，STEINHAGEN-THIESSEN E，et al．Impact of age，sex and CMV-infection on peripheral T cell phenotypes：results from the Berlin BASE-II Study［J］．Biogerontology，2015，16（5）：631-643．DOI：10.1007/s10522-015-9563-2.
［9］BULATI M，CARUSO C，COLONNA-ROMANO G.From lymphopoiesis to plasma cells differentiation，the age-related modifications of B cell compartment are influenced by “inflamm-ageing”［J］．Ageing Res Rev，2017，36：125-136．DOI：10.1016/j.arr.2017.04.001.
［10］NARADIKIAN M S，HAO Y，CANCRO M P.Age-associated B cells：key mediators of both protective and autoreactive humoral responses［J］．Immunol Rev，2016，269（1）：118-129．DOI：10.1111/imr.12380.
［11］RUBTSOVA K，RUBTSOV A V，CANCRO M P，et al．Age-associated B cells：a T-bet-dependent effector with roles in protective and pathogenic immunity［J］．J Immunol，2015，195（5）：1933-1937．DOI：10.4049/jimmunol.1501209.
［12］CANCRO M P.Age-associated B cells［J］．Annu Rev Immunol，2020，38：annurev-immunol-092419-031130．DOI：10.1146/annurev-immunol-092419-031130.
［13］TABIBIAN-KEISSAR H，HAZANOV L，SCHIBY G，et al．Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues［J］．Eur J Immunol，2016，46（2）：480-492．DOI：10.1002/eji.201545586.
［14］DE BOURCY C F，ANGEL C J，VOLLMERS C，et al．Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging［J］．Proc Natl Acad Sci USA，2017，114（5）：1105-1110．DOI：10.1073/pnas.1617959114.
［15］CEPEDA S，CANTU C，OROZCO S，et al．Age-associated decline in thymic B cell expression of Aire and Aire-dependent self-antigens［J］．Cell Rep，2018，22（5）：1276-1287．DOI：10.1016/j.celrep.2018.01.015.
［16］COOPER M A，FEHNIGER T A，CALIGIURI M A.The biology of human natural killer-cell subsets［J］．Trends Immunol，2001，22（11）：633-640．DOI：10.1016/s1471-4906（01）02060-9.
［17］LE GARFF-TAVERNIER M，BéZIAT V，DECOCQ J，et al．Human NK cells display major phenotypic and functional changes over the life span［J］．Aging Cell，2010，9（4）：527-535．DOI：10.1111/j.1474-9726.2010.00584.x.
［18］JUáREZ-VEGA G，RANGEL-RAMíREZ V，MONSIVáIS-URENDA A，et al．Comparative analysis of NK cell receptor repertoire in adults and very elderly subjects with Cytomegalovirus infection［J］．Hum Immunol，2017，78（3）：274-280．DOI：10.1016/j.humimm.2017.01.004.
［19］PRZEMSKA-KOSICKA A，CHILDS C E，MAIDENS C，et al．Age-related changes in the natural killer cell response to seasonal influenza vaccination are not influenced by a synbiotic：a randomised controlled trial［J］．Front Immunol，2018，9：591．DOI：10.3389/fimmu.2018.00591.
［20］PHAN M T，CHUN S，KIM S H，et al．Natural killer cell subsets and receptor expression in peripheral blood mononuclear cells of a healthy Korean population：reference range，influence of age and sex，and correlation between NK cell receptors and cytotoxicity［J］．Hum Immunol，2017，78（2）：103-112．DOI：10.1016/j.humimm.2016.11.006.
［21］DOGRA P，RANCAN C，MA W J，et al．Tissue determinants of human NK cell development，function，and residence［J］．Cell，2020，180（4）：749-763.e13．DOI：10.1016/j.cell.2020.01.022.
［22］KARED H，MARTELLI S，NG T P，et al．CD57 in human natural killer cells and T-lymphocytes［J］．Cancer Immunol Immunother，2016，65（4）：441-452．DOI：10.1007/s00262-016-1803-z.
［23］AL-ATTAR A，PRESNELL S R，PETERSON C A，et al．The effect of sex on immune cells in healthy aging：Elderly women have more robust natural killer lymphocytes than do elderly men［J］．Mech Ageing Dev，2016，156：25-33．DOI：10.1016/j.mad.2016.04.001.
［24］BUMGARDNER S A，ZHOU Y，JIANG Z，et al．Genetic influence on splenic natural killer cell frequencies and maturation among aged mice［J］．Exp Gerontol，2018，104：9-16．DOI：10.1016/j.exger.2018.01.010.
［25］SHEHATA H M，HOEBE K，CHOUGNET C A.The aged nonhematopoietic environment impairs natural killer cell maturation and function［J］．Aging Cell，2015，14（2）：191-199．DOI：10.1111/acel.12303.
［26］REED R G，PRESNELL S R，AL-ATTAR A，et al．Perceived stress，cytomegalovirus titers，and late-differentiated T and NK cells：between-，within-person associations in a longitudinal study of older adults［J］．Brain Behav Immun，2019，80：266-274．DOI：10.1016/j.bbi.2019.03.018.
［27］LOPEZ-SEJAS N，CAMPOS C，HASSOUNEH F，et al．Effect of CMV and aging on the differential expression of CD300a，CD161，T-bet，and eomes on NK cell subsets［J］．Front Immunol，2016，7：476．DOI：10.3389/fimmu.2016.00476.
［28］REED R G，AL-ATTAR A，PRESNELL S R，et al．A longitudinal study of the stability，variability，and interdependencies among late-differentiated T and NK cell subsets in older adults［J］．Exp Gerontol，2019，121：46-54．DOI：10.1016/j.exger.2019.03.006.
［29］JACKAMAN C，TOMAY F，DUONG L，et al．Aging and cancer：the role of macrophages and neutrophils［J］．Ageing Res Rev，2017，36：105-116．DOI：10.1016/j.arr.2017.03.008.
［30］DONG H L，ROWLAND I，THOMAS L V，et al．Immunomodulatory effects of a probiotic drink containing lactobacillus casei shirota in healthy older volunteers［J］．Eur J Nutr，2013，52（8）：1853-1863．DOI：10.1007/s00394-012-0487-1.
［31］LEFEVRE M，RACEDO S M，RIPERT G，et al．Probiotic strain bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period：a randomized，double-blind placebo-controlled study［J］．Immun Ageing，2015，12：24．DOI：10.1186/s12979-015-0051-y.
［32］PU F F，GUO Y，LI M，et al．Yogurt supplemented with probiotics can protect the healthy elderly from respiratory infections：a randomized controlled open-label trial［J］．Clin Interv Aging，2017，12：1223-1231．DOI：10.2147/CIA.S141518.
［33］LEE A，LEE Y J，YOO H J，et al．Consumption of dairy yogurt containing lactobacillus paracasei ssp.paracasei，bifidobacterium animalis ssp.lactis and heat-treated Lactobacillus plantarum improves immune function including natural killer cell activity［J］．Nutrients，2017，9（6）：E558．DOI：10.3390/nu9060558.
［34］MIYAZAWA K，KAWASE M，KUBOTA A，et al．Heat-killed lactobacillus gasseri can enhance immunity in the elderly in a double-blind，placebo-controlled clinical study［J］．Benef Microbes，2015，6（4）：441-449．DOI：10.3920/BM2014.0108.
［35］MARUYAMA M，ABE R，SHIMONO T，et al．The effects of non-viable lactobacilluson immune function in the elderly：a randomised，double-blind，placebo-controlled study［J］．Int J Food Sci Nutr，2016，67（1）：67-73．DOI：10.3109/09637486.2015.1126564.
［36］MATTEUCCI C，GRELLI S，BALESTRIERI E，et al．Thymosin alpha 1 and HIV-1：recent advances and future perspectives［J］．Future Microbiol，2017，12：141-155．DOI：10.2217/fmb-2016-0125.
［37］杨崇艳.头孢哌酮/舒巴坦联合胸腺肽α1治疗鲍曼不动杆菌重症肺炎的临床应用分析［J］．中国全科医学，2019，22（S2）：115-117.
YANG C Y.Clinical application of cefoperazone/sulbactam combined with thymosin alpha 1 in the treatment of Acinetobacter baumannii severe pneumonia［J］．Chinese General Practice，2019，22（S2）：115-117.
［38］MORRIS D C，CHEUNG W L，LOI R，et al．Thymosin β4 for the treatment of acute stroke in aged rats［J］．Neurosci Lett，2017，659：7-13．DOI：10.1016/j.neulet.2017.08.064.
［39］YE L，ZHANG P Y，DUVAL S，et al．Thymosin β4 increases the potency of transplanted mesenchymal stem cells for myocardial repair［J］．Circulation，2013，128（11 Suppl 1）：S32-41．DOI：10.1161/CIRCULATIONAHA.112.000025.
［40］BINSFELD M，HANNON M，OTJACQUES E，et al．Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and immune recovery after hematopoietic stem cell transplantation［J］．Cancer Immunol Immunother，2015，64（8）：989-998．DOI：10.1007/s00262-015-1708-2.
［41］ROMANI L，OIKONOMOU V，MORETTI S，et al．Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis［J］．Nat Med，2017，23（5）：590-600．DOI：10.1038/nm.4305.
［42］PEREZ E E，ORANGE J S，BONILLA F，et al．Update on the use of immunoglobulin in human disease：a review of evidence［J］．J Allergy Clin Immunol，2017，139（3S）：S1-46．DOI：10.1016/j.jaci.2016.09.023.
［43］BOZZO J，JORQUERA J I.Use of human immunoglobulins as an anti-infective treatment：the experience so far and their possible re-emerging role［J］．Expert Rev Anti Infect Ther，2017，15（6）：585-604．DOI：10.1080/14787210.2017.1328278.
［44］孙静洁，王琪.小剂量激素联合免疫抑制剂在Ⅰ、Ⅱ型重症肌无力患者中的疗效观察及对细胞免疫水平的影响研究［J］．中国免疫学杂志，2019，35（21）：2628-2632.
SUN J J，WANG Q.Therapeutic effect of low-dose hormone combined with immunosuppressive agents in patients with type Ⅰ and Ⅱ myasthenia gravis and its effect on cellular immunity［J］．Chinese Journal of Immunology，2019，35（21）：2628-2632.

[1]	MENG Jiangtao, YANG Siyu, SUN Lei, LEI Ruining, ZHAO Xiaoxia. Advances in the Prognostic Value of Diffusion Tensor Imaging with Motor Evoked Potential for Motor Function in Cerebral Infarction Patients with Hemiplegia [J]. Chinese General Practice, 2023, 26(32): 4098-4102.
[2]	NIU Guohui, LI Tingting, ZHU Dengna, WANG Jun, LIU Hongxing, WANG Xin, ZHANG Mengmeng, XIE Jiayang. Clinical Characteristics of Global Developmental Delay in Children of Different Genders [J]. Chinese General Practice, 2023, 26(26): 3276-3281.
[3]	YANG Xuhong, WANG Minglei, LIU Wenxiao, MA Wanlong, ZHAO Jianguo, HUANG Xueying, WANG Minxing, DING Xiangchun, WANG Xiaodong. Evaluation of Cognitive Impairment in Patients with Minimal Hepatic Encephalopathy Based on Degree Centrality of Resting-state Blood Oxygenation Level-dependent Functional Magnetic Resonance Imaging [J]. Chinese General Practice, 2023, 26(24): 3033-3041.
[4]	HE Dan, MA Jianhua, MA Juan, DU Lei, ZHANG Yan, HAO Chenguang. Expression and Significance of Regulatory B-lymphocytes in Peripheral Blood of Patients with Neuromyelitis Optica Spectrum Disorders [J]. Chinese General Practice, 2023, 26(20): 2513-2517.
[5]	ZI Jing, DU Xueping. Exploratory Research on Models of Operating Elderly Care Facilities by Community Health Institutions from Integrated Medical and Elderly Care Perspective: a Case Study of Yinling Elderly Nursing Home Held by Beijing Xicheng District Yuetan Community Health Center [J]. Chinese General Practice, 2023, 26(19): 2434-2438.
[6]	WANG Fangfang, CUI Yanru, LI Jiayu, PANG Rizhao, ZHANG Anren. Possible Mechanism of Improving Neurodegenerative Diseases via Rejuvenation of Mitochondrial Function by Intermittent Fasting [J]. Chinese General Practice, 2023, 26(12): 1530-1536.
[7]	ZHANG Jindong, ZHENG Haonan, ZHANG Tao, DUAN Liping. Effect of Microbiota-targeted Therapy on Gut Microbiota in Patients with Irritable Bowel Syndrome: a Scoping Review [J]. Chinese General Practice, 2023, 26(12): 1520-1529.
[8]	ZHANG Sen, BAI Hongying, LI Qianqian, LI Caixia. Total Deep Medullary Veins Score in Cerebral Small Vessel Disease: Association with Imaging Markers and Factors Related to Its Elevation [J]. Chinese General Practice, 2023, 26(06): 681-686.
[9]	LAN Hailong, NING Guanyuan, HUANG Xiangmin, XIAO Yeyu. Sequences of SS_TSE and Modified Abdominal T2WI Magnetic Resonance Imaging in the Diagnosis of Neonatal Pneumonia [J]. Chinese General Practice, 2023, 26(03): 308-312.
[10]	WU Xiaoran, WANG Xiaoyue, GENG Yibo, ZHANG Hongxing, ZHANG Haisan. Spontaneous Brain Activities in Hyperthyroidism Patients Assessed Using Fractional Amplitude of Low-frequency Fluctuation [J]. Chinese General Practice, 2022, 25(33): 4173-4178.
[11]	SHEN Dingyi, LI Xiaopan, MENG Fanping, LU Jingjue, ZHOU Yixin, LYU Jun. Death Status and Trends of Female Mental Disorders Patients in Pudong New Area of Shanghai, 2005-2021 [J]. Chinese General Practice, 2022, 25(32): 4072-4078.
[12]	LAO Shen, HE Jianxing, LIANG Wenhua. Targeting Pericytes for Vascular Normalization as an Emerging Strategy in Remodeling Tumor Microenvironment [J]. Chinese General Practice, 2022, 25(32): 3971-3977,F01.
[13]	Congcong ZHANG, Ya LI, Suyun LI, Jing MAO. Protective Effect of Bufei Jianpi Formula on Mucosal Barrier in a Rat Model with Chronic Obstructive Pulmonary Disease [J]. Chinese General Practice, 2022, 25(30): 3761-3767.
[14]	Yujie WANG, Jian WANG, Jingwei ZHOU. Effect of Qingre Xiaozheng Formula on Improving Renal Injury in a Rat Model of Diabetic Kidney Disease [J]. Chinese General Practice, 2022, 25(29): 3678-3685.
[15]	Xiaoyuan HUANG, Maoliti WULABIEKE·, Jilili ABUDUKEYOUMU·, Jichao WANG, Xiaopeng YANG. Application of a Neuronavigation System Utilizing 3.0T Magnetic Resonance Imaging in Frameless Stereotactic Brain Biopsies [J]. Chinese General Practice, 2022, 25(29): 3686-3690,3697.