📚 Tuberculosis (TB) | 结核病
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It mainly affects the lungs, but can also infect lymph nodes, bones, kidneys and the brain. TB remains a major global health challenge, especially in low- and middle-income countries, and is a key example of a bacterial disease in the Cambridge A-Level Biology syllabus.
结核病是由结核分枝杆菌引起的一种传染病。它主要侵犯肺部，但也可感染淋巴结、骨骼、肾脏和脑部。结核病仍然是全球重大健康挑战，尤其是在低收入和中等收入国家，并且是剑桥 A-Level 生物课程中细菌性疾病的重要例子。
1. Causative Agent and Classification | 病原体与分类
TB is caused by Mycobacterium tuberculosis, a rod-shaped, aerobic bacterium. It is classified as an acid-fast bacillus because its cell wall contains a high proportion of mycolic acid, a waxy lipid that resists Gram staining and protects the cell from desiccation and some antibiotics.
结核病由结核分枝杆菌引起，这是一种杆状、需氧的细菌。它被归类为抗酸杆菌，因为其细胞壁含有大量分枝菌酸，这是一种蜡质脂类，能抵抗革兰染色，并保护菌体免受干燥和某些抗生素的伤害。
The bacterium is slow-growing, with a generation time of about 15-20 hours. This slow growth makes laboratory culture difficult and means antibiotic treatment must be prolonged to kill dividing and dormant cells.
这种细菌生长缓慢，代时约为15-20小时。这种缓慢生长使实验室培养变得困难，也意味着抗生素治疗必须持续足够长时间，以杀死处于分裂期和休眠期的细菌。
2. Transmission | 传播途径
TB is spread through the air when an infected person with active pulmonary TB coughs, sneezes, speaks or sings. Tiny droplet nuclei containing the bacteria can remain suspended in the air for hours.
结核病通过空气传播，当活动性肺结核患者咳嗽、打喷嚏、说话或唱歌时，含有细菌的微小飞沫核可在空气中悬浮数小时。
Transmission usually requires prolonged close contact, for example within a household or crowded workplace. The bacteria enter a new host through inhalation into the alveoli.
传播通常需要长时间密切接触，例如在家庭或拥挤的工作场所内。细菌通过吸入进入新宿主并到达肺泡。
A key point is that latent TB infection is not infectious, but active pulmonary TB is highly infectious. Overcrowding, poor ventilation and weakened immunity all increase transmission risk.
关键要点是潜伏性结核感染不具有传染性，但活动性肺结核具有很强的传染性。过度拥挤、通风不良和免疫力低下都会增加传播风险。
3. Pathogenesis and Infection Process | 发病机制与感染过程
Once inhaled, M. tuberculosis reaches the alveoli, where it is engulfed by alveolar macrophages. Normally macrophages destroy bacteria by fusing the phagosome with lysosomes, but M. tuberculosis prevents this fusion and survives inside the phagosome.
结核分枝杆菌被吸入后到达肺泡，并被肺泡巨噬细胞吞噬。正常情况下巨噬细胞通过吞噬体与溶酶体融合来杀灭细菌，但结核分枝杆菌能阻止这种融合，从而在吞噬体内存活。
Infected macrophages release cytokines that attract more macrophages and T lymphocytes to the site. This leads to the formation of a granuloma, also called a tubercle, which walls off the bacteria and limits their spread.
受感染的巨噬细胞释放细胞因子，吸引更多巨噬细胞和 T 淋巴细胞到达感染部位。这导致肉芽肿（也称结核结节）的形成，将细菌包裹起来并限制其扩散。
The bacteria can also spread via lymphatic or blood vessels to other organs, causing extrapulmonary TB. In the lungs, tissue damage results from the host immune response as much as from bacterial toxins.
细菌还可通过淋巴管或血管扩散到其他器官，引起肺外结核。在肺部，组织损伤既来自宿主免疫反应，也来自细菌毒性。
4. Immune Response and Granuloma Formation | 免疫反应与肉芽肿形成
TB is controlled mainly by cell-mediated immunity rather than by antibodies. CD4⁺ helper T cells recognise mycobacterial antigens presented by macrophages and secrete interferon-gamma (IFN-γ), which activates macrophages.
结核病的控制主要依靠细胞免疫而非抗体。CD4⁺ 辅助性 T 细胞识别巨噬细胞呈递的分枝杆菌抗原，并分泌 γ-干扰素（IFN-γ），从而激活巨噬细胞。
Activated macrophages become more effective at killing intracellular bacteria and may develop into epithelioid cells. A granuloma consists of a central core of infected macrophages, often with caseous necrosis, surrounded by T cells and fibroblasts.
被激活的巨噬细胞杀灭胞内菌的能力增强，并可转变为上皮样细胞。肉芽肿由中央受感染的巨噬细胞（常伴有干酪样坏死）和周围的 T 细胞及成纤维细胞组成。
This immune response is protective but also causes tissue damage. The balance between bacterial containment and immunopathology determines the outcome of infection.
这种免疫反应具有保护作用，但也会造成组织损伤。细菌被控制的程度与免疫病理损伤之间的平衡决定了感染的结果。
5. Latent vs Active TB | 潜伏性与活动性结核
In most healthy individuals, the immune system contains the bacteria in a dormant state. This is called latent TB infection (LTBI). The person has no symptoms, is not infectious, but has viable bacteria in granulomas.
在大多数健康个体中，免疫系统将细菌控制在休眠状态，这称为潜伏性结核感染（LTBI）。患者没有症状、不具有传染性，但肉芽肿中仍有活菌存在。
Active TB occurs when the immune system fails to contain the bacteria. This can happen soon after infection (primary progressive TB) or years later when immunity weakens (reactivation TB).
当免疫系统无法控制细菌时，就会发生活动性结核病。这可能发生在感染后不久（原发性进行性结核），也可能在多年后免疫力下降时发生（再激活结核）。
About 5-10% of people with latent TB eventually develop active TB during their lifetime. Risk factors include HIV infection, diabetes, malnutrition, smoking and immunosuppressive therapy.
大约5-10%的潜伏性结核感染者最终会在一生中发展为活动性结核。危险因素包括 HIV 感染、糖尿病、营养不良、吸烟和免疫抑制治疗。
| Feature | 特征 | Latent TB | 潜伏性结核 | Active TB | 活动性结核 |
|---|---|---|
| Symptoms | 症状 | None | 无 | Cough, fever, weight loss | 咳嗽、发热、体重减轻 |
| Infectious | 传染性 | No | 无 | Yes, if pulmonary | 有，若为肺结核 |
| Bacteria | 细菌状态 | Dormant in granulomas | 肉芽肿内休眠 | Multiplying and spreading | 繁殖和扩散 |
6. Symptoms and Clinical Features | 症状与临床特征
Active pulmonary TB usually causes a persistent cough lasting more than three weeks, chest pain, and coughing up blood or sputum. Systemic symptoms include fever, night sweats, weight loss and fatigue.
活动性肺结核通常引起持续三周以上的咳嗽、胸痛，以及咯血或咳痰。全身症状包括发热、盗汗、体重减轻和乏力。
Weight loss and wasting are why TB was historically called ‘consumption’. Extrapulmonary TB can cause localised symptoms depending on the organ affected, such as back pain in spinal TB or headache in TB meningitis.
体重减轻和消瘦是结核病在历史上被称为 ‘痨病’ 的原因。肺外结核根据受累器官不同可引起局部症状，例如脊柱结核可引起背痛，结核性脑膜炎可引起头痛。
- Persistent cough with sputum or blood | 持续咳嗽，伴痰或血
- Night sweats and fever | 盗汗和发热
- Unintentional weight loss | 非刻意体重减轻
- Fatigue and malaise | 疲劳和乏力
7. Diagnosis | 诊断方法
Diagnosis of active TB often begins with a chest X-ray, which may show cavities, infiltrates or lymph node enlargement. However, X-ray findings are not specific and must be confirmed by microbiological tests.
活动性结核的诊断通常从胸部 X 线检查开始，可能显示空洞、浸润或淋巴结肿大。但 X 线表现不具特异性，必须通过微生物学检查确认。
Sputum smear microscopy uses the Ziehl-Neelsen acid-fast stain to visualise red bacilli against a blue background. It is rapid and cheap but can miss low bacterial loads. Culture on Lowenstein-Jensen medium is more sensitive but takes weeks.
痰涂片镜检采用齐尔-尼尔森抗酸染色，在蓝色背景下观察红色杆菌。该方法快速、廉价，但可能漏检细菌载量低的样本。在罗氏培养基上培养更敏感，但需要数周时间。
Molecular tests such as GeneXpert MTB/RIF detect mycobacterial DNA and common rifampicin-resistance mutations within hours. Tuberculin skin tests and interferon-gamma release assays (IGRAs) indicate immune sensitisation but cannot distinguish latent from active disease.
分子检测如 GeneXpert MTB/RIF 可在数小时内检测分枝杆菌 DNA 和常见的利福平耐药突变。结核菌素皮肤试验和 γ-干扰素释放试验（IGRA）可提示免疫致敏，但不能区分潜伏感染和活动性疾病。
8. Treatment and Antibiotic Action | 治疗与抗生素作用
Standard first-line treatment for drug-sensitive TB is a six-month course. The intensive phase lasts two months with isoniazid, rifampicin, pyrazinamide and ethambutol (HRZE), followed by a four-month continuation phase with isoniazid and rifampicin.
药物敏感性结核的标准一线治疗为六个月疗程。强化期持续两个月，使用异烟肼、利福平、吡嗪酰胺和乙胺丁醇（HRZE），随后为四个月的继续期，使用异烟肼和利福平。
Antibiotics must be taken together and for the full duration to prevent relapse and resistance. Directly observed therapy (DOT) is used in many programmes to ensure adherence.
抗生素必须联合使用并完成整个疗程，以防止复发和耐药。许多规划中采用直接面视下督导治疗（DOT）以确保依从性。
| Drug | 药物 | Target | 靶点 | Effect |
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