【1.25】新出现的病原体对免疫系统提出了新的挑战

immunobiology 阅读量：次

致病微生物已经围攻人类数百年，甚至数千年。由鼠疫耶尔森菌引起的腺鼠疫的报告可以追溯到公元前1320年的非利士人。几个世纪以来，流感病毒一直在引起人类疾病，希腊医生希波克拉底（Hippocrates）早在公元前410年就发现了一种类似流感的疾病。目前的估计表明，结核分枝杆菌（结核的病原体）已经存在了70000多年。然而，正如最近的历史所表明的，新的致病生物偶尔会出现并对人类造成破坏。通常，这些新出现的病原体是基因相对较小、突变率较高的病毒，是发展人传人能力的理想条件

21世纪初出现了几种新型冠状病毒，可引起呼吸道感染，传播率很高。这些病毒被认为是从它们的自然宿主蝙蝠传播到人类的。其中两种病毒引起了高致死率的流行，即2002-2003年的SARS-CoV和2012年的MERS-CoV，但最终每种病毒造成的死亡人数都不到1000人。第三种冠状病毒SARS-CoV-2于2019年底出现，并迅速蔓延到全球各地，引发了一场全球大流行，扰乱了社会和经济，到2020年6月，每天造成4000多人死亡。对SARS-CoV-2免疫反应的研究正在以惊人的速度进行，到2021年初，已经开发出多种有效的疫苗并向公众推出

总结

对感染的反应可以组织成几个效应器模块,各种类型的病原体生活方式。检测感染的先天性传感器细胞产生激活先天性淋巴细胞（ILCs，innate lymphoid cells）和T细胞的激发剂，从而放大免疫反应并激活各种效应器模块。ILCs包括产生不同细胞因子并激活不同效应器模块的亚群。T细胞根据共受体CD8和CD4的表达分为两大类。CD8和CD4 T细胞分别识别MHC I类或MHC II类蛋白呈递的抗原。这些T细胞的结果，就像它们的ILC对应物一样，也促进不同效应器模块的作用。NK细胞和CD8T细胞可以发挥细胞毒性活性以靶向细胞内感染，如病毒。先天性淋巴和辅助T细胞的其他亚群可以分泌激活其他效应器功能的催吐剂，这些效应器针对细胞内细菌、细胞外细菌和真菌以及寄生虫。T细胞还提供信号，帮助调节B细胞并刺激它们产生抗体。特异性抗体介导可溶性毒素和细胞外病原体的清除和消除。它们不仅与毒素或微生物上的抗原相互作用，还与多种吞噬细胞表达的特定受体的Fc区相互作用。吞噬细胞还表达沉积在微生物表面的补体蛋白受体，特别是在抗体存在的情况下

免疫失败可能是由遗传缺陷或针对免疫系统重要组成部分的感染引起的。错误的免疫反应会损害宿主组织，如自身免疫性疾病或过敏，或导致移植器官的衰竭。尽管免疫接种仍然是对抗疾病的最伟大的免疫学工具，但现代方法增加了新的工具，如单克隆抗体，自20世纪80年代中期首次使用以来，这些工具在临床上变得越来越重要。

第1章小结

免疫系统保护宿主免受感染。先天免疫是第一道防线，但缺乏识别某些病原体的能力，也缺乏提供防止再次感染的特定保护性免疫的能力。适应性免疫是基于从一系列具有高度多样的抗原特异性受体的淋巴细胞中进行克隆选择，这些受体使免疫系统能够识别任何外来抗原。在适应性免疫反应中，抗原特异性淋巴细胞增殖并分化为消除病原体的效应细胞或淋巴细胞克隆。图1.7总结了免疫反应的阶段及其大致时间。宿主防御需要不同的识别系统和多种效应器机制来寻找和摧毁体内及其内外表面不同生境中的多种病原体，它还通过克隆选择产生更多分化的记忆淋巴细胞，这使得在再次感染时能够做出更快速有效的反应。免疫学研究的主要医学目标是调节免疫反应，无论是在不需要时抑制免疫反应，还是在发生传染病时刺激免疫反应

词汇

  • effector module： A collection of cell-mediated and humoral mechanisms that involve components of both the innate and adaptive immune systems. These mechanisms act together to achieve elimination of a particular category of pathogen.

  • type 1 immunity ： Class of effector activities aimed at elimination of intracellular pathogens.

  • ILC1： A subset of innate lymphoid cells characterized by production of IFN-γ.

  • type 2 immunity： Class of effector activities aimed at elimination of parasites and promoting barrier and mucosal immunity.

  • type 3 immunity： Class of effector activities aimed at elimination of extracellular pathogens such as bacteria and fungi.

  • classes： The class of an antibody is defined by the type of heavy chain it contains. There are five main antibody classes: IgA, IgD, IgM, IgG, and IgE, containing heavy chains α, δ, μ, γ, and ε, respectively. The IgG class has several subclasses. See also isotypes.

  • isotype： The designation of an immunoglobulin chain with respect to the type of constant region it has. Light chains can be of either κ or λ isotype. Heavy chains can be of μ, δ, γ, α, or ε isotype. The different heavy-chain isotypes have different effector functions and determine the class and functional properties of antibodies (IgM, IgD, IgG, IgA, and IgE, respectively).

  • neutralization： Inhibition of the infectivity of a virus or the toxicity of a toxin molecule by the binding of antibodies.

  • Fc receptors： Family of cell-surface receptors that bind the Fc portions of different immunoglobulins: Fcγ receptors bind IgG, for example, and Fcε receptors bind IgE.

  • opsonization： The coating of the surface of a pathogen by antibody and/or complement that makes it more easily ingested by phagocytes.

  • complement activation： The activation of the normally inactive proteins of the complement system that occurs on infection. See classical pathway, alternative pathway, lectin pathway.

  • cell-mediated immune responses： An adaptive immune response in which antigen-specific effector T cells have the main role. The immunity to infection conferred by such a response is called cell-mediated immunity. A primary cell-mediated immune response is the T-cell response that occurs the first time a particular antigen is encountered.

  • CD8： The co-receptor for T-cell receptors that recognize peptide antigens bound to MHC class I molecules. It binds to the lateral face of the MHC molecule.

  • CD4： The co-receptor for T-cell receptors that recognize peptide antigens bound to MHC class II molecules. It binds to the lateral face of the MHC molecule.

  • co-receptor： Cell-surface protein that increases the sensitivity of a receptor to its ligand by binding to associated ligands and participating in signaling. The antigen receptors on T cells and B cells act in conjunction with co-receptors, which are either CD4 or CD8 on T cells, and a co-receptor complex of three proteins, one of which is the complement receptor CR2, on B cells.

  • MHC class I： Polymorphic cell-surface proteins encoded in the MHC locus and expressed on most cells. They present antigenic peptides generated in the cytosol to CD8 T cells and also bind the co-receptor CD8.

  • MHC class II： Polymorphic cell-surface proteins encoded in the MHC locus and expressed primarily on specialized antigen-presenting cells. They present antigenic peptides derived from internalized extracellular pathogens to CD4 T cells and also bind the co-receptor CD4.

  • T follicular helper (TFH)： An effector T cell found in lymphoid follicles that provides help to B cells for antibody production and class switching.

  • immunodeficiency diseases： Any inherited or acquired disorder in which some aspect or aspects of host defense are absent or functionally defective.

  • acquired immune deficiency syndrome (AIDS)： A disease caused by infection with the human immunodeficiency virus (HIV-1 or HIV2). AIDS occurs when an infected individual has lost most of his or her CD4 T cells, so that infections with opportunistic pathogens occur.

  • allergy： The state in which a symptomatic immune reaction is made to a normally innocuous environmental antigen. It involves the interaction between the antigen and antibody or primed T cells produced by earlier exposure to the same antigen.

  • autoimmune disease： Disease in which the pathology is caused by adaptive immune responses to self antigens.

  • graft rejection： The immunologically mediated rejection of grafted tissues or organs from a genetically nonidentical donor. It is due chiefly to recognition of nonself MHC molecules on the graft.

  • polymorphic： Existing in a variety of different forms; applied to a gene, occurring in a variety of different alleles.

  • monoclonal antibodies： Antibodies produced by a single clone of B lymphocytes, so that they are all identical.

  • IFN-γ： A cytokine of the interferon structural family produced by effector CD4 TH1 cells, CD8 T cells, and NK cells. Its primary function is the activation of macrophages, and it acts through a different receptor from that of the type I interferons.

  • humoral immunity, humoral immune response： Immunity due to proteins circulating in the blood, such as antibodies (in adaptive immunity) or complement (in innate immunity). Adaptive humoral immunity can be transferred to unimmunized recipients by the transfer of serum containing specific antibody.

  • TH1： A subset of effector CD4 T cells characterized by the cytokines they produce, notably IFN-γ and TNF-α. They are mainly involved in activating macrophages and promoting inflammation.

  • TH2： A subset of effector CD4 T cells that are characterized by the cytokines they produce, notably IL-4, IL-5, and IL-13. They are involved in recruiting eosinophils and activating mast cells and basophils, and in promoting enhanced barrier protection.

  • TH17： A subset of CD4 T cells that are characterized by production of the cytokine IL-17. They help recruit neutrophils to sites of infection.

  • H-2 locus, H-2 genes： The major histocompatibility complex of the mouse. Haplotypes are designated by a lowercase superscript, as in H-2b

参考资料

  • Janeway’s Immunobiology 10th edition
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