Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Hagler Institute for Advanced Study, Texas A&M University, College Station, TX, United States.
Front Immunol. 2019 Apr 3;10:684. doi: 10.3389/fimmu.2019.00684. eCollection 2019.
This treatise describes the development of immunology as a scientific discipline with a focus on its foundation. Toward the end of the nineteenth century, the study of immunology was founded with the discoveries of phagocytosis by Elias Metchnikoff, as well as by Emil Behring's and Paul Ehrlich's discovery of neutralizing antibodies. These seminal studies were followed by the discoveries of bacteriolysis by complement and of opsonization by antibodies, which provided first evidence for cooperation between acquired and innate immunity. In the years that followed, light was shed on the pathogenic corollary of the immune response, describing different types of hypersensitivity. Subsequently, immunochemistry dominated the field, leading to the revelation of the chemical structure of antibodies in the 1960s. Immunobiology was preceded by transplantation biology, which laid the ground for the genetic basis of acquired immunity. With the identification of antibody producers as B lymphocytes and the discovery of T lymphocytes as regulators of acquired immunity, lymphocytes moved into the center of immunologic research. T cells were shown to be genetically restricted and to regulate different leukocyte populations, including B cells and professional phagocytes. The discovery of dendritic cells as major antigen-presenting cells and their surface expression of pattern recognition receptors revealed the mechanisms by which innate immunity instructs acquired immunity. Genetic analysis provided in-depth insights into the generation of antibody diversity by recombination, which in principle was shown to underlie diversity of the T cell receptor, as well. The invention of monoclonal antibodies not only provided ultimate proof for the unique antigen specificity of the antibody-producing plasma cell, it also paved the way for a new era of immunotherapy. Emil Behring demonstrated cure of infectious disease by serum therapy, illustrating how clinical studies can stimulate basic research. The recent discovery of checkpoint control for cancer therapy illustrates how clinical application benefits from insights into basic mechanisms. Last not least, perspectives on immunology progressed from a dichotomy between cellular-unspecific innate immunity and humoral-specific acquired immunity, toward the concept of complementary binarity.
本文论述了免疫学作为一门科学学科的发展历程，重点介绍了其基础。19 世纪末，随着伊里亚·梅契尼科夫（Elias Metchnikoff）发现吞噬作用、埃米尔·冯·贝林（Emil Behring）和保罗·埃尔利希（Paul Ehrlich）发现中和抗体，免疫学研究得以建立。在此基础上，补体介导的细菌溶解作用和抗体介导的调理作用的发现为获得性免疫和固有免疫之间的合作提供了初步证据。此后，人们对免疫反应的发病机制有了更深入的了解，描述了不同类型的过敏反应。随后，免疫化学占据了主导地位，导致 20 世纪 60 年代揭示了抗体的化学结构。免疫生物学的前身是移植生物学，它为获得性免疫的遗传基础奠定了基础。随着抗体产生细胞（B 淋巴细胞）的鉴定和 T 淋巴细胞作为获得性免疫调节剂的发现，淋巴细胞成为免疫研究的中心。T 细胞被证明具有遗传限制，并调节不同的白细胞群体，包括 B 细胞和专业吞噬细胞。树突状细胞作为主要抗原呈递细胞及其表面模式识别受体的表达揭示了固有免疫指导获得性免疫的机制。遗传分析深入了解了抗体多样性的产生机制，该机制在原理上表明其为 T 细胞受体多样性的基础。单克隆抗体的发明不仅为浆细胞产生的抗体的独特抗原特异性提供了最终证据，也为免疫治疗的新时代铺平了道路。埃米尔·冯·贝林通过血清疗法证明了传染病的治愈，说明了临床研究如何刺激基础研究。最近发现的癌症治疗检查点控制表明，基础机制的见解如何使临床应用受益。最后但同样重要的是，免疫学的观点从细胞非特异性固有免疫和体液特异性获得性免疫之间的二分法，发展到互补二元性的概念。
