Ventura Maria Teresa, Casciaro Marco, Gangemi Sebastiano, Buquicchio Rosalba
Department of Interdisciplinary Medicine, University of Bari, Policlinico, Piazza G. Cesare no 11, 70124 Bari, Italy.
School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Clin Mol Allergy. 2017 Dec 14;15:21. doi: 10.1186/s12948-017-0077-0. eCollection 2017.
The immunosenescence is a relatively recent chapter, correlated with the linear extension of the average life began in the nineteenth century and still in progress. The most important feature of immunosenescence is the accumulation in the "immunological space" of memory and effector cells as a result of the stimulation caused by repeated clinical and subclinical infections and by continuous exposure to antigens (inhalant allergens, food, etc.). This state of chronic inflammation that characterizes senescence has a significant impact on survival and fragility. In fact, the condition of frail elderly occurs less frequently in situations characterized by poor contact with viral infections and parasitic diseases. Furthermore the immunosenescence is characterized by a particular "remodelling" of the immune system, induced by oxidative stress. Apoptosis plays a central role in old age, a period in which the ability of apoptosis can change. The remodelling of apoptosis, together with the Inflammaging and the up-regulation of the immune response with the consequent secretion of pro-inflammatory lymphokines represents the major determinant of the rate of aging and longevity, as well as of the most common diseases related with age and with tumors. Other changes occur in the innate immunity, the first line of defence providing rapid, but unspecific and incomplete protection, consisting mostly of monocytes, natural killer cells and dendritic cells, acting up to the establishment of a adaptive immune response, which is slower, but highly specific, which cellular substrate consists of T and B lymphocytes. The markers of "Inflammaging" in adaptive immunity in centenarians are characterized by a decrease in T cells "naive." The reduction of CD8 virgins may be related to the risk of morbidity and death, as well as the combination of the increase of CD8+ cells and reduction of CD4+ T cells and the reduction of CD19+ B cells. The immune function of the elderly is weakened to due to the exhaustion of T cell-virgin (CD95-), which are replaced with the clonal expansion of CD28-T cells.
The increase of pro-inflammatory cytokines is associated with dementia, Parkinson's disease, atherosclerosis, diabetes type 2, sarcopenia and a high risk of morbidity and mortality. A correct modulation of immune responses and apoptotic phenomena can be useful to reduce age-related degenerative diseases, as well as inflammatory and neoplastic diseases.
免疫衰老这一领域相对较新，它与始于19世纪且仍在持续的平均寿命的线性延长相关。免疫衰老的最重要特征是，由于反复的临床和亚临床感染以及持续接触抗原（吸入性过敏原、食物等）所引起的刺激，记忆细胞和效应细胞在“免疫空间”中积累。这种表征衰老的慢性炎症状态对生存和脆弱性有重大影响。事实上，在与病毒感染和寄生虫病接触较少的情况下，体弱老年人的情况较少出现。此外，免疫衰老的特征是由氧化应激诱导的免疫系统的特定“重塑”。细胞凋亡在老年期起着核心作用，在这个时期细胞凋亡的能力会发生变化。凋亡的重塑，连同炎症衰老以及免疫反应的上调以及随之而来的促炎细胞因子的分泌，是衰老和长寿速度以及与年龄和肿瘤相关的最常见疾病的主要决定因素。先天性免疫也会发生其他变化，它是第一道防线，提供快速但非特异性且不完整的保护，主要由单核细胞、自然杀伤细胞和树突状细胞组成，一直作用到适应性免疫反应建立，适应性免疫反应较慢但高度特异性，其细胞底物由T和B淋巴细胞组成。百岁老人适应性免疫中“炎症衰老”的标志物的特征是T细胞“幼稚”状态的减少。CD8原始细胞的减少可能与发病和死亡风险有关，以及CD8 +细胞增加、CD4 + T细胞减少和CD19 + B细胞减少的综合情况。老年人的免疫功能因原始T细胞（CD95 -）的耗竭而减弱，这些细胞被CD28 - T细胞的克隆扩增所取代。
促炎细胞因子的增加与痴呆、帕金森病、动脉粥样硬化、2型糖尿病、肌肉减少症以及高发病和死亡风险相关。正确调节免疫反应和凋亡现象可能有助于减少与年龄相关的退行性疾病以及炎症和肿瘤性疾病。
