Costimulatory and coinhibitory mechanisms appear to be involved throughout immune responses to control their specificity and level. Many mechanisms operate; therefore, various theoretical models should be considered complementary rather than competing. One such coinhibitory model, pictured in 1971, involves the crosslinking of antigen receptors with inhibitory Fc receptors by antigen/antibody complexes. This model was prompted by observations that the Fc portion of antibody was required for potent suppression of immune responses by antibody. The signal via the antigen receptor wakes up T or B cells, providing specificity, while costimulators and coinhibitors stimulate or inhibit these awoken cells. The recent observations that administration of monoclonal anti-SARS-CoV-2 spike antibodies in early COVID-19 patients inhibits the induction of clinically damaging autoimmune antibodies suggest they may provide negative Fc signals that are blocked in COVID-19 patients. Furthermore, the reduced ability of SARS-CoV-2 antigen to localize to germinal centres in COVID-19 patients also suggests a block in binding of the Fc of antibody bound to antigen on FcγRIIb of follicular dendritic cells. The distinction between self and foreign is made not only at the beginning of immune responses but also throughout, and involves multiple mechanisms and models. There are past beginnings (history of models) and current and future beginnings for solving serious clinical problems (such as COVID-19) and different types of models used for understanding the complexities of fundamental immunology.

中文翻译：

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共抑制的开始

共刺激和共抑制机制似乎涉及整个免疫反应，以控制它们的特异性和水平。许多机制在运作；因此，应将各种理论模型视为互补而非竞争。1971 年描绘的一种这样的共抑制模型涉及抗原受体与抑制性 Fc 受体通过抗原/抗体复合物的交联。该模型是由观察结果提示的，即抗体的 Fc 部分是抗体有效抑制免疫反应所必需的。通过抗原受体的信号唤醒 T 或 B 细胞，提供特异性，而共刺激物和共抑制剂刺激或抑制这些唤醒细胞。最近的观察结果表明，在早期 COVID-19 患者中使用单克隆抗 SARS-CoV-2 刺突抗体会抑制具有临床破坏性的自身免疫抗体的诱导，这表明它们可能提供在 COVID-19 患者中被阻断的阴性 Fc 信号。此外，SARS-CoV-2 抗原定位到 COVID-19 患者生发中心的能力降低也表明，与滤泡树突细胞 FcγRIIb 上抗原结合的抗体的 Fc 结合受阻。自身与外源的区分不仅在免疫反应开始时进行，而且贯穿整个过程，涉及多种机制和模型。