2010补体PPT课件.ppt

Complement Jules Bordet (1870-1961), Discoverer of complement Discoverer of complement 不溶菌 溶菌 muddy clear Complement refers to fresh serum capable of lysing antibody (Ab)-coated cells. This activity is destroyed (inactivated) by heating serum at 56 ℃ for 30 minutes. 补体（complement） 广泛存在于血清、组织液和细胞膜表面的一组经活化具有酶活性的蛋白质，是一个具有精密调控机制的蛋白质反应系统。 - Complement system consists of approximately 30 serum molecules include soluble and membrane binding proteins. 补体系统：由30余种可溶性蛋白质和膜结合蛋白组成的多分子系统，具有酶的活性和自我调节作用。 Complement system Nomenclature of complement C1(q, r, s), C2, …C9 factor B, factor P, factor H Complement regulatory proteins named from its functions, e.g. C1 INH, C4bp On cleavage(裂解) of a complement component, the larger product is given the suffix ‘b’ and the smaller ‘a’, e.g. C3a, C3b A bar over a complex denotes enzymic activity, e.g. C1、C3bBb Letter ‘i’ denotes inactivity, e.g. iC3b Components Innate component: – C1q, C1r, C1s, C4, C2 – MBL (mannose binding lectin ), MASP (mannan associated serine protease) – factor B, factor D – C3, C5-9(common pathway) Regulatory proteins: Properdin, C1 INH, factor I, C4bp, factor H, etc. Complement receptors: CR (CR1-5, C3aR, C5aR, C1qR) 补体的固有成分： 补体调节蛋白：包括备解素、I因子、C1抑制物等 补体受体：包括CR1~CR5、C3aR等 共包含 30 余种 经典激活途径的C1q、C1r、C1s、C4、C2 甘露糖结合凝集素(MBL)激活途径的MBL、丝氨酸蛋白酶 旁路激活途径的B因子、D因子 共同末端通路的C3、C5、C6、C7、C8和C9。 补体系统的特点 1、连锁反应性：级联反应 关键成分常以酶原形式存在，活化后形成级联反应（cascade）。 2、非特异性：属于非特异性天然免疫系统 不因为特异性抗原刺激而改变，天然存在于人体内。 3、不稳定性： 代谢率居血浆各成分之首，许多成分对热敏感，易灭活 4、来源广泛 以肝脾巨噬细胞合成为主，但很多其他细胞、器官都可以合成，约占血清总量的10%左右。 Section 2 Complement activation Pathways of complement activation 既独立又交差，不仅是机体固有免疫防御的重要部分，也是抗体发挥免疫效应的主要机制之一。 P49 the first section Classical pathway of complement activation Recognition phase Activators :Immune complex (IC) Activation conditions: - C1 activated only by binding to IgM CH3 and IgG1, IgG2, IgG3 CH2 domains. - One C1 activated needs at least two Ig Fc to bind. - Soluble antibody can’t activate complement. Componets:C1（