📚 Autoimmune Diseases – A Case of Mistaken Identity | 自身免疫疾病——身份误认案例
The immune system normally protects the body by recognising and destroying pathogens while leaving healthy tissues untouched. Autoimmune diseases arise when this recognition fails and the immune system attacks the body's own cells as if they were foreign invaders – a case of mistaken identity.
免疫系统通常通过识别并消灭病原体来保护身体，同时不损伤健康组织。当这种识别机制失效，免疫系统将自身细胞当作外来入侵者攻击时，就会发生自身免疫疾病——这是一种身份误认。
1. The Immune System's Identity Check | 免疫系统的身份识别
Lymphocytes must be able to distinguish self from non-self. T cells recognise peptide antigens presented on major histocompatibility complex (MHC) molecules, while B cells recognise intact antigens through surface immunoglobulins. In health, lymphocytes that strongly bind self antigens are eliminated or suppressed.
淋巴细胞必须能够区分自身与非自身。T细胞识别由主要组织相容性复合体（MHC）分子呈递的肽抗原，而B细胞则通过表面免疫球蛋白识别完整抗原。在健康状态下，与自身抗原有强结合的淋巴细胞会被清除或抑制。
MHC class I molecules are found on nearly all nucleated cells and present intracellular peptides to CD8⁺ cytotoxic T cells. MHC class II molecules are mainly on antigen-presenting cells and present extracellular peptides to CD4⁺ helper T cells. This system is designed to detect infection, but it also creates a constant risk of recognising self peptides.
MHC I 类分子几乎存在于所有有核细胞上，将细胞内肽段呈递给 CD8⁺ 细胞毒性 T 细胞。MHC II 类分子主要位于抗原呈递细胞上，将细胞外肽段呈递给 CD4⁺ 辅助 T 细胞。该系统旨在检测感染，但也始终存在识别自身肽段的风险。
2. Self-Tolerance: Central and Peripheral | 中枢与外周自身耐受
Central tolerance occurs in the thymus for T cells and in the bone marrow for B cells. Immature T cells that recognise self MHC-peptide complexes with high affinity are removed by negative selection. Thymic medullary epithelial cells express many tissue-specific antigens under the control of the AIRE gene, allowing deletion of T cells that would otherwise attack organs such as the pancreas or thyroid.
中枢耐受发生在T细胞的胸腺和B细胞的骨髓中。以高亲和力识别自身MHC-肽复合物的未成熟T细胞通过阴性选择被清除。胸腺髓质上皮细胞在AIRE基因控制下表达许多组织特异性抗原，从而删除那些原本会攻击胰腺或甲状腺等器官的T细胞。
Peripheral tolerance provides a second layer of protection. Regulatory T cells (Treg) expressing FOXP3 suppress autoreactive lymphocytes, and some self-reactive T cells become anergic because they receive antigen signals without costimulation. Immune-privileged sites, such as the brain and eye, also limit immune attack.
外周耐受提供了第二层保护。表达FOXP3的调节性T细胞（Treg）抑制自身反应性淋巴细胞，一些自身反应性T细胞由于在缺乏共刺激的情况下接受抗原信号而进入无反应状态。脑和眼等免疫豁免部位也限制了免疫攻击。
3. When Tolerance Fails: Defining Autoimmunity | 耐受失效：自身免疫的定义
Autoimmune disease occurs when central and peripheral tolerance break down and an immune response is mounted against self antigens. The result is chronic inflammation and tissue damage. Autoimmune diseases can be organ-specific, such as type 1 diabetes, or systemic, such as systemic lupus erythematosus.
当中枢和外周耐受崩溃，免疫系统对自身抗原产生免疫应答时，就会发生自身免疫疾病。结果是慢性炎症和组织损伤。自身免疫疾病可以是器官特异性的，如1型糖尿病，也可以是全身性的，如系统性红斑狼疮。
The table summarises some well-known autoimmune diseases and their targets.
下表总结了一些常见自身免疫疾病及其靶点。
| Disease | 疾病 | Main target | 主要靶点 | Typical autoantibody / effector | 典型自身抗体/效应物 |
|---|---|---|
| Type 1 diabetes | 1型糖尿病 | Pancreatic β cells | 胰岛β细胞 | Anti-insulin, anti-GAD65, T cells | 抗胰岛素、抗GAD65抗体、T细胞 |
| Rheumatoid arthritis | 类风湿性关节炎 | Synovial joints | 滑膜关节 | Rheumatoid factor, anti-CCP | 类风湿因子、抗CCP抗体 |
| Multiple sclerosis | 多发性硬化 | Myelin sheaths in CNS | 中枢神经系统髓鞘 | Autoreactive T cells, oligoclonal IgG | 自身反应性T细胞、寡克隆IgG |
| Myasthenia gravis | 重症肌无力 | Acetylcholine receptors at neuromuscular junction | 神经肌肉接头乙酰胆碱受体 | Anti-AChR antibodies | 抗AChR抗体 |
| Graves' disease | Graves病 | TSH receptor on thyroid cells | 甲状腺细胞TSH受体 | Thyroid-stimulating immunoglobulins | 甲状腺刺激性免疫球蛋白 |
4. Type 1 Diabetes: Attacking Beta Cells | 1型糖尿病：攻击
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