某些革兰氏阴性细菌激活补体的新途径

巳被公认的补体系统漱活途径有两条:一条是以抗原抗体复合物为“激活剂”激活C₁的经典途径,另一条是不依赖抗体直接激活C₃的替代途径。用补体对7种革兰氏阴性细菌做溶菌试验,发现E.coli B、E.coli K₁₂gal⁺可不依赖特异性抗体而激活补体系统的经典途径,这是又一条补体系统的激活途径。     

肝素的抗补体作用

1929年Ecker和Gross发现了肝素的抗补体作用。当时认为,抗补体作用可能系肝素作用于补体的第三或第四成分(C_3,C_4),使其灭活。随后的报告肯定了这一发现。目前认为,肝素可作用于补体系统的经典途径、替代途径和调控机制,以发挥抗补体作用。一、阻抑经典途径的激活补体系统经典途径的激活是由于C_1活化而启动的。C_1活化通过两种方式进行:(1)抗原抗体复合物形成后,暴露了抗体上的补体结合点(即C_(1q)受体),血清中呈活性状态的     

MBL调控MASP激活补体系统

甘露聚糖结合凝集素(MBL;或甘露聚糖结合蛋白,MBP)是由相同的多肽链组成的寡聚物,它通过结合细胞表面的碳水化合物能够有效地识别侵入体内的多种致病微生物,并激活补体来杀灭病原微生物。MBL能与血清中其相关蛋白酶(MASP)结合,MASP包含3个丝氨酸蛋白酶MASP-1、MASP-2、MASP-3和非酶蛋白MAp19。研究显示,MBL通过2种机理调控MASP-2的活性,在先天性免疫中具有重要的作用。本文简要综述MBL调控MASP激活补体的作用机理。     

补体C3促进HIV-1感染的作用

补体是天然免疫的重要组成部分。C3是补体经典途径、旁路途径及甘露糖结合凝集素(MBL)途径的共同通路,在补体清除1型人免疫缺陷病毒(HIV-1)的过程中发挥重要作用。同时,C3在促进病毒黏膜进入、传播与储存、感染免疫细胞等方面也起重要作用。     

C型凝集素

C型凝集素（C-type lectin）代表一个识别碳水化合物配体依赖于钙离子（Ca2＋）参与的糖原结合蛋白家族,含有一个或多个一级结构和二级结构同源的碳水化合物识别结构域。随着研究的深入,越来越多的C型凝集素能够识别体内的非糖类的配体,包括蛋白质和脂类等。这些C型凝集素在维持机体稳态、免疫防御以及免疫监视等重要生理病理过程中发挥着重要作用。就C型凝集素的结构、分类和在免疫系统中的功能作一介绍。     

七鳃鳗血清中补体C3和VLRB介导的免疫防御

日本七鳃鳗（Lampetra japonica）属最原始的无颌类脊椎动物,是研究免疫起源与进化的重要模式生物。七鳃鳗血清中C3分子(L-C3)是其含量最高的补体成分,在补体经典激活途径和旁路激活途径中均发挥重要作用。本文通过PCR扩增获取C3分子α-γ链的基因序列,构建到原核表达载体pET-28a,成功在大肠杆菌中表达C3部分蛋白质并制备多克隆抗体。利用流式细胞术和激光共聚焦证明,L-C3分布在神经轴体的胞浆中。免疫共沉淀及细胞沉积结果显示,七鳃鳗血清中,VLRB与L-C3蛋白相互作用并共沉积于靶细胞膜表面。天然L-C3和VLRB清除实验,验证其在参与七鳃鳗血清杀伤靶细胞时发挥重要作用。本研究为七鳃鳗补体系统的研究奠定了基础,为七鳃鳗免疫起源与进化提供重要资料。     

甘露糖结合蛋白的结构与功能

甘露糖结合蛋白是Ｃ型动物凝集素家族一员,由肝脏分泌,存在于肝肝及血液中,其收白质结构类似于补体Ｃｌｑ。它能识别并结合某些细胞,真菌,病毒,寄生虫,肿瘤的表面糖类结构,并能激活补体系统的经典与旁路途径, 免疫防御及免疫监视中有重要意义。     

抗补体活性多糖

补体系统在宿主免疫中具有重要的作用。近年来,由某些中药中纯化的多糖具有明显的抗补体作用。这些多糖大多数含有阿拉伯糖、半乳糖和半乳糖醛酸,分子量范围6.000到500.000。它们的结构很复杂,多为具聚鼠李半乳糖醛酸结构中心的酸性杂多糖和果胶类多糖。这些多糖的抗补体活性可能和整个大分子的结构有关。一旦发生降解活性就大为下降甚至消失。它们都可以经典的方式激活补体系统。大部分也可以改变的方式激活补体系统。     

甘露聚糖结合凝集素相关丝氨酸蛋白酶

甘露聚糖结合凝集素（MBL）是一种重要的天然免疫防御分子,通过激活MBL相关丝氨酸蛋白酶（MAST）而启动补体激活凝集素途径来清除病原体。本文就MASP的基因、分子结构及功能等方面研究概况作一介绍。     

译名“补体激活的替代途径”应当废除

当初在翻译the alternative pathway of complement activation这个术语时,译者对alternative的词意以及该途径的本质有认识上的误解,将其译成补体激活的替代途径。替代,是把一种物质或一种过程去置换另一种物质或另一种过程的意思。而alternative pathway则我行我素。它不替代其他反应,其它途径也不能替代它,所以谈不上什么替代。真正具有明确替代意义的英文单词是substitutive而非alternative。     

THE MECHANISM OF COMPLEMENT FIXATION

1. Complement fixation is obtained in every antigen-antibody reaction involving the presence or formation of a heterogeneous phase (red cells, bacteria, precipitate). 2. The physical constants of fixation (temperature coefficient, velocity, quantitative relationships between the reactants) are those commonly associated with adsorption processes, and are the same in the three types of fixation studied. 3. All the in vitro immune reactions involve an aggregation of immune-serum globulins upon the surface of the antigen. It has been shown that the "fixation" of complement is an adsorption by the aggregates so formed; whether these aggregates are visible as a flocculent precipitate (e.g., sheep serum vs. anti-serum) or concentrated as a surface film on a cellular antigen (sensitized cells; agglutinated bacteria), the reaction is fundamentally the same. 4. As yet, it is unknown whether this adsorption is determined by the physical state of the precipitate, and thus, differs only quantitatively from that by Kaolin, charcoal, normal bacteria, heat-denatured proteins, etc.; or whether the comparatively enormous avidity of these aggregates for complement is due to a specific chemical affinity.     

THE MECHANISM OF COMPLEMENT ACTION

It has been shown: 1. That complement exposed to ultra-violet light is not thereby sensitized to the action of heat (which indicates that it is not protein). 2. That inactivation of complement by ultra-violet light is accompanied by a decrease in its surface tension. 3. That photoinactivation of complement is not a result of any changes in hydrogen ion concentration since these are less than 0.05 pH. 4. That hydrogen ion concentrations high enough to transform serum proteins from the cation to the anion condition (i.e. past the isoelectric point) permanently inactivate complement. These facts together with those given in previous papers lead to the following hypotheses. 1. That there is present in serum a hemolytic substance which is formed from a precursor (which may resemble lecithin) and is constantly being formed and simultaneously being broken down into inactive products. 2. That both precursor and lysin contain the same photosensitive molecular group. 3. That the lytic substance is dependent for its activity upon the state of the serum proteins.     

MECHANISM OF HEMOLYSIS BY COMPLEMENT : I. COMPLEMENT FIXATION AS AN ESSENTIAL PRELIMINARY TO HEMOLYSIS.

1. Sensitization confers upon the red cell the property of adsorbing complement from solution. The submicroscopic film of immune serum protein deposited upon the cell surface during sensitization, and completely analogous to the precipitate formed in a soluble antigen-antibody reaction (e.g., sheep serum vs. rabbit anti-sheep serum) acts as absorbent, the degree of sensitization (size of the film) determining the amount of complement "fixed" (adsorbed). 2. This adsorption of complement by the sensitized cell is an essential preliminary to hemolysis, and when inhibited, even large quantities of demonstrably active complement have no hemolytic action. The marked influence of electrolytes and of the hydrogen ion concentration upon hemolysis is due primarily to corresponding effects upon the fixation of complement by the sensitized cell. In the case of salts with monovalent cations, complement fixation (and hemolysis) is completely inhibited at any concentration < 0.02 M or > 0.35 M. Electrolytes with bivalent cations are much more inhibitory, and in low as concentration 0.07 M completely prevent fixation (and hemolysis). The optimal reaction for complement fixation (and hemolysis) is pH 6.5 to 8.0. In slightly more acid range both are inhibited. But at a reaction pH 5.3, and in the alkaline range, there is an irreversible inactivation of complement, complete at pH 4.8 and 8.8 respectively. It is perhaps more than a coincidence that complement fixation, and therefore, hemolysis, are prevented by just those factors which suppress the ionization of serum proteins, and lead to an increased aggregation state. Between a suspension of macroscopically visible particles of euglobulin in distilled water, and a solution is physiological saline, there is certainly a gradual transition, manifested at low electrolyte concentrations by the opacity of the solution. At pH 7.4, globulin would ionize as a Na-salt, an ionization inhibited as the isoelectric point (5.3) is approached, with a coincident greater tendency of the globulin to separate from solution. And the cataphoretic velocity of particles of globulin, as well as all the other properties which are a function of its ionization (viscosity, osmotic pressure, etc.), are suppressed by electrolytes, the degree of suppression being determined by the concentration and valence of the cation (on the alkaline side of the isoelectric point). The analogy with complement fixation is too complete to be dismissed as fortuitous. 3. The fact that the degree of complement "fixation" increases with the degree of sensitization explains one of the most puzzling phenomena in hemolysis,—that immune serum and complement are, to a certain extent, interchangeable, a decrease in either factor being compensated by an increase in the other (8), (20), (22). The explanation is evident from Figs. 1,2, and 3. The exact quantitative relationships involved will be developed in a later paper. With increasing sensitization there is an enormously more complete and more rapid fixation of complement, and correspondingly more rapid hemolysis, exactly the effect produced by increasing the quantity of complement instead of amboceptor (Fig. 3). All other variables being constant, the velocity of hemolysis is determined by the amount of complement adsorbed. With more amboceptor, a greater proportion is "fixed" by the cell; with more complement, a smaller proportion, but a larger absolute amount. The result is the same: more complement adsorbed, and a corresponding acceleration of hemolysis. If this mobilization of complement is the sole function of immuneserum (and there is as yet no reason to assume any other), then the accepted terminology, in which amboceptor, immune body, and hemolysin are used synonymously, is erroneous. The immune body would function only as an "amboceptor," mobilizing the effective hemolysin, complement, upon the surface of the cell. Nothing has been said of the multiple components into which complement may be split. A priori, it would be expected that the adsorption demonstrated is of the so called midpiece fraction.