第十章 免疫性疾病正常的免疫功能免疫感染免疫监视免疫稳定第一节 自身免疫性疾病几个概念（1）免疫耐受（2）自身免疫反应（3）自身免疫性疾病一、自身免疫性疾病的发病机制免疫耐受的丢失及隐蔽抗原的暴露（1）回避T细胞的耐受：分子修饰；协同刺激分子；（2）交叉免疫反应（3)Ts和Th细胞功能失衡（4）隐蔽抗原的释放遗传因素 自身免疫病与遗传因素有较密切的关系，下列事实可说明这一情况：很多自身免疫病如SLE、自身免疫性溶血性贫血、自身免疫性甲状腺炎等均具有家族史。有些自身免疫病与HLA抗原表达的类型有联系，例如人类强直性脊柱炎与HLAB27关系密切。微生物因素（1）抗原性质变异：）抗原性质变异：机体对于原本耐受的自身抗原，由于物理、化学药物、微生物等因素的是影响而发生变性、降解，暴露了新的抗原决定簇。例如变性的球蛋白因暴露新的抗原决定簇而获得抗原性，从而诱发自身抗体（类风湿因子）。或通过修饰原本耐受抗原的截体部分，从而回避了TH细胞的耐受，导致免疫应答。这是由于大部分的自身抗原属于一种半抗原和载体的复合体，其中B细胞识别的是半抗原的决定簇，T细胞识别的是载体的决定簇，引起免疫应答时二种信号缺一不可，而一般机体对自身抗原的耐受性往往只是限于T细胞，如载体的抗原决定簇经过修饰，即可为T细胞识别，而具有对该抗原发生反应潜能的B细胞一旦获得TH的信号，就会分化、增殖，产生大量自身抗体。自身免疫性疾病往往具有以下共同特点：患者有明显的家族倾向性，不少与HLA抗原尤其是与D/DR基因位点相关，女性多于男性；血液中存在高滴度自身抗体和（或）能与自身组织成分起反应的致敏淋巴细胞；疾病常呈现反复发作和慢性迁延的过程；病因大多不明，少数由药物（免疫性溶血性贫血、血小板减少性紫癜）、外伤（交感性眼炎）等所致；可在实验动物中复制出类似人类自身免疫病的模型。自身免疫性疾病分类：（一）器官特异性自身免疫病组织器官的病理损害和功能障碍仅限于抗体或致敏淋巴细胞所针对的某一器官。（二）系统性自身免疫病由于抗原抗体复合物广泛沉积于血管壁等原因导致全身多器官损害，称系统性自身疫病。习惯上又称之为胶原病或结缔组织病，这是由于免疫损伤导致血管壁及间质的纤维素样坏死性炎及随后产生多器官的胶原纤维增生所致。自身免疫性疾病的类型系统性红斑狼疮病因与发病机制病因与发病机制病理变化病理变化： 基本病变：急性坏死性小动脉炎、细动脉炎（1）皮肤：面部蝶形红斑LM：表皮萎缩、角化过度、毛囊角质栓形成、基底细胞液化表皮和真皮交界处水肿，基底膜、小动脉和真皮的胶原纤维可发生纤维素样坏死免疫荧光 ：表皮和真皮交界处有IgG、IgM及C3沉积形成颗粒状或团块状荧光（狼疮带）（2）肾狼疮性肾炎 内皮下有大量免疫复合物沉积（3）心非细菌性疣赘性心内膜炎（4）关节（5）脾小动脉周围纤维化，形成洋葱皮样The young woman has a malar rash (the so-called butterfly rash because of the shape across the cheeks). Such a rash suggests lupus. Discoid lupus erythematosus (DLE) involves mainly just the skin and is, therefore, relatively benign compared to systemic lupus erythematosus (SLE). In either case, sunlight exposure accentuates this erythematous rash. A small number (5 to 10%) of DLE patients go on to develop SLE (usually the DLE patients with a positive ANA).Here is a more severe inflammatory skin infiltrate in the upper dermis of a patient with SLE in which the basal layer is undergoing vacuolization and dissolution, and there is purpura with RBCs in the upper dermis (which are the reason for the If an immunofluorescence stain with antibody to complement or immunoglobulin is performed, then one can see the brightly fluorescing band along the dermal epidermal junction that indicates immune complex deposits are presentHere is another immunofluorescence staining pattern with antibody to IgG showing evidence for immune complexes at the dermal-epidermal junction. If such a pattern is seen only in skin involved by a rash, then the diagnosis is probably DLE, but if this pattern appears even in skin uninvolved by a rash, then the diagnosis is SLE.The periarteriolar fibrosis (onion skinning) seen in the spleen in patients with SLE at autopsy is quite striking, though of no major clinical consequence. This results from vasculitis.类风湿性关节炎 多发性和对称性增生性滑膜炎病理变化：（1）关节病变：滑膜细胞增生肥大；滑膜下结缔组织炎症细胞浸润；血管新生明显；覆盖软骨表面形成血管翳（2）关节以外的病变病因和发病机制第二节 免疫缺陷病原发性免疫缺陷病继发性免疫缺陷病获得性免疫缺陷综合征（AIDS)艾滋病病因和发生机制 病因: HIV HIV-1(AH及O 9个亚型) HIV-2Gag核心蛋白Pol逆转录酶Env糖蛋白传播途径: 性接触传播 应用污染的针头作静脉注射 输血和血制品的应用 垂直传播和哺乳The life cycle of HIV shown with the points at which pharmacologic agents may block viral maturation, including points for inhibition of reverse transcriptase, integrase, TAT transcription, and protease, in this diagram.病理变化淋巴组织的变化早期，淋巴结肿大，镜下淋巴小结 明显增生，生发中心活跃，髓质内浆细胞浸润 滤泡外层淋巴细胞减少、消失，小血管增生，生发中心被零落分割，副皮质区的CD4+细胞进行性减少，浆细胞浸润晚期，淋巴细胞几乎消失已尽继发性感染肺孢子虫、弓形虫恶性肿瘤Kaposi肉瘤Kaposis sarcoma typically produces one or more reddish purple nodules on the skin, as seen here grossly.Kaposis sarcoma microscopically produces slit-like vascular spaces in the dermis of the skin, seen here in the patch stage of KS.Kaposis sarcoma microscopically produces slit-like vascular spaces in the dermis of the skin, seen here as a noduleVisceral involvement with Kaposis sarcoma in AIDS is common. Here are multiple reddish nodules seen over the gastric mucosa