血小板减少性紫癜发病机制课件

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,特发性血小板减少性紫癜（Idiopathic Thrombocytopenic Purpura,ITP）,发病机制,特发性血小板减少性紫癜（Idiopathic Thromb,发病机制体液免疫,1体液免疫因素,自身抗体识别的靶抗原几乎涉及血小板膜表面所有分子(抗血小板糖蛋白IIb/IIIa、Ib/IX、Ia/IIa、IV、VI和P-Sel等)。,结合自身抗体的血小板易被网状内皮系统破坏,自身抗体引起获得性血小板功能异常,自身抗体结合巨核细胞，干扰巨核细胞分化成熟,McMillan等发现，2/3 ITP患者血浆能明显抑制巨核细胞生成2595%）,巨核细胞数量和成熟度均受到抑制。Chang等也证实自身抗体明显抑制脐血来源巨核细胞生长,Blood ;103:1364-1369,Blood ;102:887-895,发病机制体液免疫 1体液免疫因素,发病机制体液免疫,1、血小板相关抗体（platelet-associated immuoglobulin PAIgG）,Harrington 等1951年证实：27例ITP患者的血浆输给正常志愿者，16例PC减少,PC50109/L时，90%的患者PAIgG升高,70%患者为IgG，亦可为IgA、IgM、PAC3、PAC4,发病机制体液免疫1、血小板相关抗体（platelet-a,发病机制体液免疫,1975年，Dixon等定量检测ITP患者PAIgG,PAIgG的性质有3 种可能性：,PAIgG是血小板自身抗体，通过F(ab)片段与血小板自身抗原结合,PAIgG是循环中的免疫复合物，由免疫复合物中的IgG Fc片段与血小板膜上的Fc 受体结合,PAIgG是非特异性吸附的血浆球蛋白，血小板上的IgG亚型与血清中IgG亚型的比例是一致的,发病机制体液免疫1975年，Dixon等定量检测ITP患者,结合自身抗体的血小板易被网状内皮系统破坏,自身抗体引起获得性血小板功能异常,抗GPb 20.,阻断共刺激信号的传递可以抑制自身反应性T细胞的,特发性血小板减少性紫癜（Idiopathic Thrombocytopenic Purpura,ITP）,PAIgG的性质有3 种可能性：,Trend toward Th1 activation.,血小板自身抗体的产生部位：主要在脾脏，骨髓,抗GPb/a 32.,自身抗体识别的靶抗原几乎涉及血小板膜表面所有分子(抗血小板糖蛋白IIb/IIIa、Ib/IX、Ia/IIa、IV、VI和P-Sel等)。,have no detectible antibodies on their platelets,血小板破坏的场所：目前认为主要器官有脾脏、肝脏和骨髓，脾脏是主要场所。,PC CD8+T cells.,Trend toward Th1 activation.,primarily react with GPIIb/IIIa.,Adherent cell(APC)dependent.,T Cell Characteristics:CD4+T,Approximately 40%of patients with chronic AITP,have no detectible antibodies on their platelets,or in their plasma.,Why?,How are their platelets being destroyed?,Approximately 40%of patients,Tumor,cell,CTL,TumorCTL,Anderson et al.Nature Medicine,CD8 cell,Platelet,Lysis(kill),Suggests that a novel therapeutic targeting,cell mediated immunity may benefit some ITP patients.,Anderson et al.Nature Medicin,Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura,apoptotic resistance of activated T-lymphocytes in patients with active ITP may lead to defective clearance of autoreactive T-lymphocytes through AICDactivation induced cell death),which might cause a continued immune destruction of platelets,Olsson B,et al.Thromb Haemost.,Disturbed apoptosis of T-cells,发病机制,3、雌激素,4、遗传因素 HLA DRW9 和HLA DQW3,发病机制3、雌激素,谢谢观看,谢谢观看,