Cellular and Humoral Immune Responses in Covid-19 and Immunotherapeutic Approaches.
Cellular and Humoral Immune Responses in Covid-19 and Immunotherapeutic Approaches.
复制标题
Covid-19中的细胞和体液免疫应答及免疫学方法。
DOI：
10.2147/itt.s280706
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发表时间：
2021
影响因子：
7.2
通讯作者：
Al-Mulla F
中科院分区：
文献类型：
--
作者：
Hasan A;Al-Ozairi E;Al-Baqsumi Z;Ahmad R;Al-Mulla F
2019年冠状病毒病(新冠肺炎)是由新型冠状病毒严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的，其严重程度从无症状到严重/危重疾病不等。SARS-CoV-2使用血管紧张素转换酶2感染细胞，导致强烈的炎症反应，这种反应在进展为严重新冠肺炎的患者中最为明显。最近的研究已经开始揭示疾病严重程度不同的患者对SARS-CoV-2的先天和获得性免疫反应的一些差异。这些研究将严重形式的新冠肺炎归因于先天免疫反应功能障碍，例如I型干扰素反应延迟和/或缺陷，加上夸大和/或适应性免疫功能障碍。重症患者的T细胞(包括CD_4~+T细胞、CD_8~+T细胞、T滤泡辅助细胞、γδ-T细胞和调节性T细胞)和B细胞(过渡性细胞、双阴性2细胞、抗体分泌细胞)的反应与轻症患者不同。此外，中和抗体反应的动力学/滴度的差异已在严重疾病中被描述，这可能被抗体依赖的增强所混淆。重要的是，先前存在的针对I型干扰素的自身抗体的存在被描述为严重/危重疾病的主要原因。此外，预先接种疫苗和多次接种疫苗、训练有素的先天免疫、交叉反应免疫和血清免疫印记都可能影响疾病的严重程度和预后。几种治疗和预防方法正在进行深入的研究；这些方法包括疫苗(其中三种已通过第三阶段临床试验)、治疗性抗体和免疫抑制剂。
Coronavirus disease 2019 (Covid-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can range in severity from asymptomatic to severe/critical disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 to infect cells leading to a strong inflammatory response, which is most profound in patients who progress to severe Covid-19. Recent studies have begun to unravel some of the differences in the innate and adaptive immune response to SARS-CoV-2 in patients with different degrees of disease severity. These studies have attributed the severe form of Covid-19 to a dysfunctional innate immune response, such as a delayed and/or deficient type I interferon response, coupled with an exaggerated and/or a dysfunctional adaptive immunity. Differences in T-cell (including CD4+ T-cells, CD8+ T-cells, T follicular helper cells, γδ-T-cells, and regulatory T-cells) and B-cell (transitional cells, double-negative 2 cells, antibody-secreting cells) responses have been identified in patients with severe disease compared to mild cases. Moreover, differences in the kinetic/titer of neutralizing antibody responses have been described in severe disease, which may be confounded by antibody-dependent enhancement. Importantly, the presence of preexisting autoantibodies against type I interferon has been described as a major cause of severe/critical disease. Additionally, priorVaccine and multiple vaccine exposure, trained innate immunity, cross-reactive immunity, and serological immune imprinting may all contribute towards disease severity and outcome. Several therapeutic and preventative approaches have been under intense investigations; these include vaccines (three of which have passed Phase 3 clinical trials), therapeutic antibodies, and immunosuppressants.