📚 Tuberculosis (TB) | 结核病
Tuberculosis (TB) is a chronic, communicable disease caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs (pulmonary TB) but can spread to other organs, including the lymph nodes, bones, and brain. TB remains one of the world’s deadliest infectious diseases, and understanding its biology is central to the Cambridge International A-Level syllabus on infectious disease, immunity, and public health.
结核病是由结核分枝杆菌引起的一种慢性传染病。它主要侵犯肺部（肺结核），但也可能扩散到淋巴结、骨骼和大脑等其他器官。结核病至今仍是全球最致命的传染病之一，理解其生物学机制是剑桥国际A-Level课程中传染病、免疫和公共卫生部分的核心内容。
1. What is Tuberculosis? | 结核病是什么？
Tuberculosis is a disease that has afflicted humans for thousands of years. It is characterised by the formation of granulomas (tubercles) in infected tissues, leading to tissue damage and, in active cases, severe respiratory symptoms. The disease follows a complex natural history: after initial infection, the host immune system usually contains the bacteria in a dormant state known as latent TB infection (LTBI). In about 5–10% of infected individuals, the infection reactivates and progresses to active TB, which can be fatal without treatment.
结核病是一种困扰人类数千年的疾病。其特点是在感染组织中形成肉芽肿（结核结节），导致组织损伤；活动性病例会出现严重的呼吸道症状。该病有复杂的自然史：初次感染后，宿主免疫系统通常将细菌控制在休眠状态，称为潜伏性结核感染。在约5–10%的感染者中，感染会重新激活并发展为活动性结核，若不治疗可能致命。
2. Causative Agent: Mycobacterium tuberculosis | 病原体：结核分枝杆菌
The pathogen responsible for TB is Mycobacterium tuberculosis, an aerobic, rod-shaped bacterium. It is classified as an acid-fast bacillus because of the high lipid content in its cell wall, mainly mycolic acids. This waxy coat makes the bacterium resistant to many common disinfectants, desiccation, and antibiotics, and it retains the red dye in the Ziehl-Neelsen stain. The bacterium grows very slowly, with a generation time of 15–20 hours, which complicates both diagnosis and treatment.
引起结核病的病原体是结核分枝杆菌，一种需氧的杆状细菌。由于其细胞壁中脂质（主要是分枝菌酸）含量很高，它被归类为抗酸杆菌。这层蜡质外衣使细菌对许多常用消毒剂、干燥和抗生素具有抵抗力，并在齐尔-尼尔森染色中保留红色染料。该菌生长非常缓慢，代时为15–20小时，这使得诊断和治疗都变得复杂。
3. Transmission of TB | 结核病的传播
TB is spread through the air when a person with active pulmonary or laryngeal TB coughs, sneezes, sings, or speaks, generating droplet nuclei (1–5 µm in diameter) that contain the bacteria. These tiny particles can remain suspended in the air for several hours. Infection occurs when a susceptible individual inhales the droplet nuclei, which then reach the alveoli in the lungs. Transmission is most likely in crowded, poorly ventilated environments. Bovine TB, caused by M. bovis, can be transmitted to humans by consuming unpasteurised milk, though this route is now rare in developed countries.
结核病通过空气传播。活动性肺结核或喉结核患者在咳嗽、打喷嚏、唱歌或说话时，会产生含有细菌的飞沫核（直径1–5微米）。这些微小颗粒可在空气中悬浮数小时。当易感者吸入这些飞沫核时，它们会到达肺部肺泡，从而导致感染。在拥挤、通风不良的环境中传播最易发生。由牛分枝杆菌引起的牛结核病可通过饮用未经巴氏消毒的牛奶传播给人类，但这一途径在发达国家现已少见。
4. Primary Infection and the Host Response | 原发感染与宿主反应
When M. tuberculosis reaches the alveoli, it is engulfed by alveolar macrophages. However, the bacterium possesses virulence factors that prevent the fusion of the phagosome with lysosomes, allowing it to survive and replicate inside the macrophage. Infected macrophages release cytokines that recruit more macrophages and T lymphocytes to the site, initiating an inflammatory response. This initial focus of infection is called the Ghon focus. Bacteria may also spread via regional lymph nodes, forming the Ghon complex. In most immunocompetent individuals, the immune system controls the infection without any symptoms — this is the primary infection stage.
当结核分枝杆菌到达肺泡时，会被肺泡巨噬细胞吞噬。但该菌拥有阻止吞噬体与溶酶体融合的毒力因子，使其能够在巨噬细胞内生存和复制。受感染的巨噬细胞释放细胞因子，将更多的巨噬细胞和T淋巴细胞招募到病灶，引发炎症反应。这个最初的感染灶称为贡氏病灶。细菌还可能通过局部淋巴结扩散，形成贡氏复合征。在大多数免疫功能正常的人中，免疫系统能在无任何症状的情况下控制感染——这便是原发感染阶段。
5. Granuloma Formation and Latent TB | 肉芽肿形成与潜伏性结核
As the cellular immune response intensifies, activated macrophages cluster around infected macrophages, forming a granuloma, also known as a tubercle. The granuloma has a central core of infected macrophages and may undergo caseous necrosis (cheese-like tissue death). Fibroblasts wall off the structure, and lymphocytes surround it. Inside the granuloma, bacteria can persist for years in a dormant state. This condition is termed latent TB infection (LTBI). Individuals with LTBI have no symptoms, are not infectious, but may test positive on TB screening tests. The granuloma represents a balance between bacterial persistence and host containment.
随着细胞免疫应答增强，活化的巨噬细胞聚集在受感染的巨噬细胞周围，形成肉芽肿（又称结核结节）。肉芽肿的中心主要由受感染的巨噬细胞组成，并可能发生干酪样坏死。成纤维细胞将这一结构包裹起来，淋巴细胞围绕其周围。在肉芽肿内部，细菌可以休眠状态存活多年。这种状态被称为潜伏性结核感染。潜伏感染者没有症状，不具有传染性，但结核病筛查试验可能呈阳性。肉芽肿体现了细菌持续存在与宿主控制之间的平衡。
6. Active TB Disease: Symptoms and Progression | 活动性结核：症状与进展
When the immune system is weakened — for example, by HIV infection, malnutrition, diabetes, or immunosuppressive drugs — the granuloma may break down, releasing viable bacteria. This leads to reactivation TB (post-primary TB). Typical symptoms of active pulmonary TB include a persistent cough lasting more than three weeks, often with blood-stained sputum (haemoptysis), chest pain, night sweats, fever, weight loss, and extreme fatigue. Extrapulmonary TB can affect the pleura, lymph nodes, spine (Pott’s disease), kidneys, and meninges. Without treatment, active TB has a high mortality rate.
当免疫系统因HIV感染、营养不良、糖尿病或免疫抑制药物等因素削弱时，肉芽肿可能破裂，释放出有活力的细菌，导致再活动性结核（原发后结核）。活动性肺结核的典型症状包括持续超过三周的咳嗽，常伴有血痰（咯血）、胸痛、盗汗、发热、体重减轻和极度疲劳。肺外结核可累及胸膜、淋巴结、脊柱（波特病）、肾脏和脑膜。若不治疗，活动性结核的死亡率很高。
7. Immune Response to TB | 结核病的免疫应答
Protective immunity against TB is primarily cell-mediated, not humoral. Antigen-presenting cells (mainly dendritic cells and macrophages) present mycobacterial antigens to CD4+ T helper cells, polarising them towards a Th1 response. Th1 cells secrete interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), which activate macrophages to kill intracellular mycobacteria more effectively. CD8+ cytotoxic T cells can also recognise infected macrophages and induce apoptosis. The tuberculin skin test (Mantoux test) demonstrates a delayed-type hypersensitivity reaction — a classic cell-mediated immune response. However, a strong immune response can also contribute to tissue destruction.
对结核病的保护性免疫主要是细胞介导的，而非体液免疫。抗原提呈细胞（主要是树突状细胞和巨噬细胞）将分枝杆菌抗原提呈给CD4+ T辅助细胞，使其极化为Th1应答。Th1细胞分泌干扰素-γ和肿瘤坏死因子-α，激活巨噬细胞以更有效地杀灭胞内分枝杆菌。CD8+细胞毒性T细胞也能识别受感染的巨噬细胞并诱导凋亡。结核菌素皮肤试验（曼托试验）表现出迟发型超敏反应——典型的细胞介导免疫反应。然而，强烈的免疫应答也可能加剧组织破坏。
8. Diagnosis of TB | 结核病的诊断
Several methods are used to diagnose TB. Microscopic examination of sputum smears using the Ziehl-Neelsen stain detects acid-fast bacilli and is rapid but has limited sensitivity. Culture on Löwenstein-Jensen medium is more sensitive but can take 4–8 weeks. Molecular tests such as the GeneXpert MTB/RIF assay detect M. tuberculosis DNA and can simultaneously identify rifampicin resistance within hours. For LTBI, the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs, such as QuantiFERON-TB Gold) are employed. Chest X-rays can show typical apical infiltrates and cavitation in active pulmonary TB.
诊断结核病有多种方法。使用齐尔-尼尔森染色法对痰涂片进行显微镜检查可检出抗酸杆菌，速度虽快但灵敏度有限。在罗氏培养基上培养灵敏度更高，但可能需要4–8周。GeneXpert MTB/RIF等分子检测可在数小时内检出结核分枝杆菌DNA，并同时识别利福平耐药性。对于潜伏性结核感染，通常使用结核菌素皮肤试验和干扰素-γ释放试验（如QuantiFERON-TB Gold）。胸部X光片可显示活动性肺结核典型的肺尖浸润和空洞形成。
9. Antibiotic Treatment and DOTS Strategy | 抗生素治疗与DOTS策略
Active TB is treated with a standard six-month regimen of four first-line antibiotics: isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB) for the first two months, followed by INH and RIF for a further four months. Isoniazid inhibits mycolic acid synthesis, rifampicin blocks bacterial RNA polymerase, pyrazinamide targets membrane transport, and ethambutol inhibits arabinogalactan synthesis. The World Health Organization promotes the Directly Observed Treatment, Short-course (DOTS) strategy, where healthcare workers watch patients swallow each dose to ensure adherence and prevent resistance.
活动性结核采用标准六个月治疗方案，前两个月使用四种一线抗生素：异烟肼、利福平、吡嗪酰胺和乙胺丁醇，随后四个月继续使用异烟肼和利福平。异烟肼抑制分枝菌酸合成，利福平阻断细菌RNA聚合酶，吡嗪酰胺作用于膜转运，乙胺丁醇抑制阿拉伯半乳聚糖合成。世界卫生组织推广直接面视下短程化疗（DOTS）策略，由卫生工作者监督患者服用每一剂药物，以确保依从性并防止耐药。
10. Drug-Resistant TB: MDR-TB and XDR-TB | 耐药性结核：MDR-TB和XDR-TB
Drug resistance in TB arises from spontaneous chromosomal mutations in the target genes, and it is amplified by inappropriate or incomplete treatment. Multidrug-resistant TB (MDR-TB) is defined as resistance to at least isoniazid and rifampicin, the two most powerful first-line drugs. Extensively drug-resistant TB (XDR-TB) is MDR-TB with additional resistance to any fluoroquinolone and at least one of the injectable second-line drugs (e.g., amikacin, kanamycin, capreomycin). Treating drug-resistant TB requires longer regimens with less effective, more toxic, and more expensive second-line agents.
结核病耐药性源于靶基因的自发染色体突变，不当或未完成的治疗会加剧这一问题。耐多药结核（MDR-TB）指至少对异烟肼和利福平这两种最有效的一线药物耐药。广泛耐药结核（XDR-TB）是在MDR-TB基础上，还对任一氟喹诺酮类药物以及至少一种注射用二线药物（如阿米卡星、卡那霉素或卷曲霉素）耐药。治疗耐药结核需要使用疗程更长、效果较差、毒性更大且费用更高的二线药物。
11. TB and HIV Co-infection | 结核病与艾滋病毒共感染
HIV infection is the strongest known risk factor for developing active TB. HIV destroys CD4+ T cells, severely weakening the cell-mediated immune response essential for granuloma maintenance. As a result, HIV-positive individuals are much more likely to progress from latent TB infection to active disease. TB is a leading cause of death among people living with HIV. Co-infection poses challenges in drug interactions between antiretroviral therapy (ART) and TB medications, particularly rifampicin and protease inhibitors. Integrated TB-HIV services are crucial for effective management.
HIV感染是发展为活动性结核的最强风险因素。HIV破坏CD4+ T细胞，严重削弱维持肉芽肿所必需的细胞介导免疫应答。因此，HIV阳性者从潜伏性结核感染进展为活动性疾病的几率大大增加。结核病是HIV感染者死亡的主要原因。共感染给抗逆转录病毒治疗与抗结核药物（尤其是利福平和蛋白酶抑制剂）之间的相互作用带来了挑战。结核-HIV一体化服务对于有效管理至关重要。
12. Prevention: BCG Vaccine and Public Health | 预防：卡介苗与公共卫生
The Bacille Calmette-Guérin (BCG) vaccine, a live attenuated strain of Mycobacterium bovis, is the only currently available vaccine against TB. It is most effective at preventing severe forms of TB in children, such as miliary TB and tuberculous meningitis, but its efficacy against pulmonary TB in adults is highly variable. In many countries with high TB burden, BCG is given at birth. Other preventive measures include identifying and treating LTBI (e.g., with isoniazid preventive therapy), improved ventilation, use of respirators, and early case detection. Global TB control relies on the End TB Strategy, aiming to reduce TB incidence and mortality drastically by 2030.
卡介苗是目前唯一可用的结核病疫苗，它是牛分枝杆菌的减毒活菌株。它在预防儿童严重结核病（如粟粒性结核和结核性脑膜炎）方面非常有效，但对成人肺结核的保护效力差异很大。在许多结核病高负担国家，卡介苗在出生时便接种。其他预防措施包括识别并治疗潜伏性结核感染（例如异烟肼预防性治疗）、改善通风、使用防护口罩以及早期发现病例。全球结核病控制依赖“终止结核病策略”，目标是在2030年前大幅降低结核病的发病率和死亡率。
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