📚 Defence against disease | 防御疾病
The human body is constantly exposed to a wide variety of pathogens, including bacteria, viruses, fungi and parasites. To survive, the body relies on a layered defence system that prevents entry, limits spread and eliminates invaders. These defences are broadly categorised into non-specific (innate) mechanisms and specific (adaptive) immune responses. Together, they recognise and remember threats, providing short-term protection and long-lasting immunity.
人体持续暴露于多种病原体，包括细菌、病毒、真菌和寄生虫。为了生存，机体依赖分层防御系统来阻止入侵、限制扩散并清除入侵者。这些防御机制大致分为非特异性（固有性）和特异性（适应性）免疫应答。二者协同识别并记忆威胁，提供即时保护及长久免疫力。
1. Physical barriers as the first line of defence | 第一道防线的物理屏障
The skin is the most extensive physical barrier. Its outer layer, the epidermis, consists of dead, keratinised cells that are difficult for pathogens to penetrate. Continuous shedding of surface cells also removes attached microbes. Intact skin thus provides a formidable mechanical block.
皮肤是最广泛的物理屏障。其外层表皮由死亡、角化的细胞组成，使病原体难以穿透。表层细胞不断脱落也能清除附着的微生物。因此，完整的皮肤构成了坚固的机械屏障。
Mucous membranes lining the respiratory, digestive and urogenital tracts secrete sticky mucus that traps pathogens. In the airways, ciliated epithelial cells beat in a coordinated manner to sweep mucus and trapped particles toward the throat, where they are swallowed or coughed out. This mucociliary escalator is a key defence in the lungs.
覆盖呼吸道、消化道和泌尿生殖道的黏膜分泌黏稠黏液，能黏住病原体。在气道中，纤毛上皮细胞协调摆动，将黏液及捕获的颗粒推向喉部，随后被吞咽或咳出。这一黏液纤毛梯级系统是肺部防御的关键。
2. Chemical defences at body surfaces | 体表的化学防御
Tears and saliva contain lysozyme, an enzyme that hydrolyses the peptidoglycan cell walls of bacteria, causing them to burst. Sebum secreted by sebaceous glands on the skin contains fatty acids that lower pH, creating an acidic environment hostile to many microbes. The stomach produces hydrochloric acid, giving gastric juice a pH as low as 1.5–2.0, which denatures proteins and kills most ingested bacteria.
泪液和唾液含有溶菌酶，该酶能水解细菌的肽聚糖细胞壁，使其破裂。皮肤皮脂腺分泌的皮脂含脂肪酸，降低pH值，形成不适于多种微生物的酸性环境。胃分泌盐酸，使胃液pH低至1.5–2.0，使蛋白质变性并杀死大多数随食物进入的细菌。
In addition, antimicrobial peptides called defensins are produced by epithelial cells and phagocytes; they disrupt microbial membranes and enhance innate immunity.
此外，上皮细胞和吞噬细胞产生称为防御素的抗微生物肽，可破坏微生物膜并增强固有免疫。
3. Second line of defence: non-specific cellular responses | 第二道防线：非特异性细胞应答
If pathogens breach surface barriers, they encounter the innate cellular defence. The key players are phagocytes – mainly neutrophils and macrophages. Phagocytosis begins with chemotaxis, where phagocytes are attracted to the site of infection by chemical signals, such as cytokines released by damaged tissues and bacterial peptides. The phagocyte then attaches to the pathogen, often aided by opsonins like antibodies or complement proteins that mark the invader.
若病原体突破了体表屏障，就会遇到固有细胞防御。主角是吞噬细胞——主要是中性粒细胞和巨噬细胞。吞噬作用始于趋化，即吞噬细胞被损伤组织释放的细胞因子及细菌肽等化学信号吸引至感染部位。随后吞噬细胞附着于病原体，通常借助抗体或补体蛋白等调理素标记入侵者。
The phagocyte engulfs the pathogen by extending pseudopodia around it, forming an internal vesicle called a phagosome. Lysosomes then fuse with the phagosome to create a phagolysosome, where digestive enzymes and reactive oxygen species destroy the microbe. The debris is exocytosed or presented on the cell surface as antigens.
吞噬细胞伸出伪足包裹病原体，形成称为吞噬体的囊泡。随后溶酶体与吞噬体融合形成吞噬溶酶体，其中的消化酶和活性氧物质将微生物杀灭降解。残渣被胞吐排出，或处理为抗原呈递于细胞表面。
4. Inflammation and fever | 炎症与发热
Tissue injury or infection triggers an inflammatory response. Damaged mast cells and basophils release histamine, which causes local arterioles to vasodilate and capillary permeability to increase. This results in redness, heat, swelling and pain. The increased blood flow delivers more phagocytes, complement proteins and clotting factors to the site. The raised temperature locally inhibits pathogen replication.
组织损伤或感染触发炎症反应。受损的肥大细胞和嗜碱性粒细胞释放组胺，引起局部小动脉血管舒张及毛细血管通透性增加，导致红、热、肿、痛。增加的血流带来了更多吞噬细胞、补体蛋白和凝血因子。局部温度升高也抑制了病原体的复制。
Systemically, pyrogens released by phagocytes act on the hypothalamus to raise the body’s set point, causing fever. Moderate fever enhances phagocyte activity and limits the growth of certain pathogens, while also speeding up repair processes.
全身性上，吞噬细胞释放的致热原作用于下丘脑，调高体温设定点，引起发热。适度发热可增强吞噬细胞活性，限制某些病原体生长，同时加速修复过程。
5. Introducing specific immunity: antigens and recognition | 特异性免疫入门：抗原与识别
The adaptive immune system provides a response tailored to a particular pathogen. It relies on the recognition of antigens – molecules (usually proteins or polysaccharides) that the body identifies as foreign. Each B and T lymphocyte carries unique receptors that can bind to a specific antigen. This is the basis of clonal selection: a pathogen activates only those lymphocytes with matching receptors, causing them to proliferate and differentiate.
适应性免疫系统提供针对特定病原体的精准应答。它依赖于识别抗原——即被机体识别为异物的分子（通常是蛋白质或多糖）。每个B淋巴细胞和T淋巴细胞表面带有独特的受体，可与特定抗原结合。这就是克隆选择的原理：病原体仅激活拥有匹配受体的淋巴细胞，使其增殖分化。
Self-tolerance is established during lymphocyte development in the bone marrow and thymus; any cells that react strongly to self-antigens are eliminated, preventing autoimmune diseases.
在骨髓和胸腺中，淋巴细胞发育过程中建立了自身耐受；对自身抗原有强烈反应的细胞被清除，以防自身免疫病。
6. Humoral immunity: B cells and antibody production | 体液免疫：B细胞与抗体产生
Humoral immunity targets pathogens in the body fluids. When a naive B cell encounters its specific antigen, it internalises, processes and presents it on MHC class II molecules. Binding to an activated T helper cell (CD4⁺) provides the necessary co-stimulation. This leads to clonal expansion and differentiation into plasma cells and memory B cells.
体液免疫针对体液中的病原体。当初始B细胞遭遇其特异性抗原后，内吞、处理并用MHC II类分子呈递抗原。与活化的T辅助细胞（CD4⁺）结合提供必要的共刺激，从而引起克隆扩增并分化为浆细胞和记忆B细胞。
Plasma cells are antibody factories, secreting vast quantities of soluble glycoproteins known as antibodies or immunoglobulins (Ig). These antibodies circulate in the blood and lymph, binding to antigens and neutralising toxins, agglutinating pathogens and marking them for destruction by phagocytes or complement. Memory B cells persist for years and enable a faster, stronger secondary response upon re-infection.
浆细胞是抗体工厂，分泌大量可溶性糖蛋白，即抗体或免疫球蛋白(Ig)。这些抗体在血液和淋巴中循环，与抗原结合，中和毒素，凝集病原体并标记它们供吞噬细胞或补体消灭。记忆B细胞可存活多年，在再次感染时引发更快速、更强烈的二次应答。
7. Cell-mediated immunity: T lymphocytes in action | 细胞免疫：T淋巴细胞的作用
Cell-mediated immunity primarily combats intracellular pathogens, such as viruses that have infected host cells, as well as cancer cells and transplanted tissues. T helper cells (CD4⁺) are central coordinators. When they bind antigen-MHC II complexes on antigen-presenting cells like dendritic cells, they become activated and secrete cytokines that stimulate B cells, cytotoxic T cells and macrophages.
细胞免疫主要负责对抗细胞内病原体，如已感染宿主细胞的病毒，以及癌细胞和移植组织。T辅助细胞（CD4⁺）是核心协调者。当它们与树突状细胞等抗原呈递细胞上的抗原-MHC II类复合物结合时被激活，分泌细胞因子刺激B细胞、细胞毒T细胞及巨噬细胞。
Cytotoxic T cells (CD8⁺) recognise antigen-MHC I complexes on infected or abnormal cells. Upon activation, they release perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and trigger apoptosis, effectively destroying the infected cell without releasing newly assembled viruses.
细胞毒T细胞（CD8⁺）识别受感染细胞或异常细胞上的抗原-MHC I类复合物。激活后，它们释放穿孔素和颗粒酶。穿孔素在靶细胞膜上形成孔道，颗粒酶进入后引发细胞凋亡，从而在消灭感染细胞的同时不释放新组装的病毒。
8. Antibody structure and function | 抗体的结构与功能
An antibody molecule is a Y-shaped glycoprotein consisting of four polypeptide chains: two identical heavy chains and two identical light chains, held together by disulfide bonds. Each chain has a variable (V) region at the tip of the arms, which forms the antigen-binding site unique to each antibody, and a constant (C) region that determines the antibody class and effector function. The hinge region provides flexibility.
抗体分子是Y形糖蛋白，由四条多肽链组成：两条相同的重链和两条相同的轻链，通过二硫键连接。每条链在臂端处有可变区(V)，构成每个抗体独特的抗原结合位点，以及决定抗体类别和效应功能的恒定区(C)。铰链区赋予分子柔性。
There are five classes of immunoglobulins (IgM, IgG, IgA, IgD, IgE). IgG is the major circulating antibody, crossing the placenta to provide passive immunity to the fetus. IgA is found in secretions such as saliva, tears and breast milk, protecting mucosal surfaces. IgM is the first antibody produced in an immune response.
免疫球蛋白分五类（IgM、IgG、IgA、IgD、IgE）。IgG是主要循环抗体，能穿过胎盘给胎儿提供被动免疫。IgA存在于唾液、泪液和乳汁等分泌物中，保护黏膜表面。IgM是免疫应答中最早产生的抗体。
9. Active and passive immunity | 主动免疫与被动免疫
Active immunity develops when the body’s own immune system encounters an antigen and produces antibodies and memory cells. This can occur naturally via infection or artificially through vaccination. The response is slower to develop initially but is long-lasting because of immunological memory.
主动免疫在机体自身免疫系统遭遇抗原并产生抗体和记忆细胞时形成。可自然发生（感染）或人工通过疫苗接种实现。初次应答较慢，但因免疫记忆作用持续时间长久。
Passive immunity is the transfer of pre-formed antibodies from another source. Natural passive immunity is acquired by a fetus across the placenta (IgG) or by a newborn through colostrum and breast milk (IgA). Artificial passive immunity involves injecting antibodies, such as antivenom or monoclonal antibodies. Protection is immediate but temporary, as the antibodies are eventually degraded and no memory cells are formed.
被动免疫是从外部获取预先合成的抗体。天然被动免疫由胎儿通过胎盘获得(IgG)或新生儿通过初乳及母乳获得(IgA)。人工被动免疫涉及注射抗体，如抗蛇毒血清或单克隆抗体。保护即刻生效但短暂，因为抗体最终会被降解，且不形成记忆细胞。
10. Vaccination and herd immunity | 疫苗接种与群体免疫
Vaccines contain antigens derived from pathogens in a form that does not cause disease but still stimulates an adaptive immune response. They may consist of inactivated whole pathogens, live attenuated organisms, purified components (subunit vaccines) or genetic material encoding antigens (mRNA and DNA vaccines). Following vaccination, the primary immune response generates memory B and T cells, so that upon exposure to the actual pathogen, the secondary response is rapid and vigorous, preventing illness.
疫苗含有源自病原体但不会致病的抗原形式，可刺激适应性免疫应答。疫苗种类包括灭活全病原体、减毒活疫苗、纯化成分（亚单位疫苗）以及编码抗原的遗传物质（mRNA和DNA疫苗）。接种后，初次免疫应答产生记忆B、T细胞，当遭遇真实病原体时，二次应答快速强烈，从而预防疾病。
When a high proportion of a population is immunised, herd immunity arises, reducing the spread of infection and protecting individuals who cannot be vaccinated, such as those with compromised immunity. This is crucial for eradicating or controlling diseases like polio and measles.
当人群中高比例个体免疫接种后，产生群体免疫，减少感染传播，并保护无法接种疫苗者（如免疫功能低下者）。这对于根除或控制脊髓灰质炎、麻疹等疾病至关重要。
11. Monoclonal antibodies in diagnosis and therapy | 单克隆抗体在诊断与治疗中的应用
Monoclonal antibodies (mAbs) are identical antibodies produced by hybridoma cells formed by fusing a specific B lymphocyte with a myeloma (cancer) cell. The hybridoma retains the B cell’s ability to produce a single antibody type and the cancer cell’s capacity for continuous division. This technology yields unlimited quantities of highly specific antibodies.
单克隆抗体（mAbs）是由特定B淋巴细胞与骨髓瘤（癌）细胞融合形成的杂交瘤细胞产生的相同抗体。杂交瘤保留了B细胞生产单一抗体类型的能力和癌细胞持续分裂的能力。这项技术可产出无限量高度特异性的抗体。
In medicine, mAbs are used for targeted drug delivery – for example, conjugating a cytotoxic drug to an antibody that binds to cancer cells only (e.g. trastuzumab for HER2-positive breast cancer). They are also employed in diagnostic tests, such as pregnancy test kits that detect hCG, and in passive immunisation against respiratory syncytial virus (palivizumab) for high-risk infants. Monoclonal antibodies thus extend specific immunity into therapeutic interventions.
在医学中，单抗用于靶向药物递送——例如，将细胞毒药物连接到仅结合癌细胞的抗体上（如赫赛汀用于HER2阳性乳腺癌）。它们也用于诊断检测，如检测hCG的验孕棒，以及高危婴儿预防呼吸道合胞病毒的被动免疫（帕利珠单抗）。因此，单克隆抗体将特异性免疫扩展至治疗干预。
12. Integration and overview | 体系与总结
The defence against disease is a multi-level system. Physical and chemical barriers provide the first containment; non-specific cellular and inflammatory responses offer rapid but generic elimination; the adaptive immune system ensures precise recognition and immunological memory. Collaboration between humoral and cell-mediated arms maximises protection, while vaccination and passive immunisation harness these principles for public and personalised health. Understanding these processes allows scientists to develop novel therapies, such as monoclonal antibodies and next-generation vaccines, to combat emerging infectious diseases.
防御疾病是多层次体系。物理与化学屏障提供第一道阻控；非特异性细胞及炎症应答提供快速但泛泛的清除；适应性免疫系统确保精准识别和免疫记忆。体液免疫与细胞免疫分支的协同使防护最大化，而疫苗接种和被动免疫则将这些原理用于公共卫生与个体化医疗。理解这些过程使科学家能开发新疗法，如单克隆抗体和新一代疫苗，以对抗新发传染病。
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