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铜绿假单胞菌黏液型胞外多糖的免疫原性特性

Immunogenic properties of Pseudomonas aeruginosa mucoid exopolysaccharide.

作者信息

Garner C V, DesJardins D, Pier G B

机构信息

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.

出版信息

Infect Immun. 1990 Jun;58(6):1835-42. doi: 10.1128/iai.58.6.1835-1842.1990.

Abstract

Previous studies have shown that antibodies to Pseudomonas aeruginosa mucoid exopolysaccharide (MEP) can be divided into two types on the basis of their functional activity. One type is able to mediate opsonic killing in conjunction with leukocytes and complement, and the other type is not. We investigated, in mice, the properties of this antigen associated with elicitation of opsonic killing antibody. We found that smaller-sized material (Kav = 0.26), which has been tested as a human vaccine, elicited opsonic killing antibody in mice at low doses (1 to 10 micrograms) and at doses of greater than or equal to 40 micrograms, only nonopsonic killing antibody was produced. A similar dose effect was seen with heat-killed mucoid P. aeruginosa cells. After immunization with high doses of this MEP or the heat-killed cells, the mice were refractory to induction of opsonic killing antibody no matter what dose of MEP was used as a booster. In contrast, a larger-molecular-weight preparation (Kav = 0.05) elicited opsonic killing antibody over a wide dose range (1 to 400 micrograms). Additionally, 50 micrograms of the larger-sized preparation could overcome the suppression induced by 50 micrograms of the smaller material. Suppression elicited by 50 micrograms of the smaller material could be adoptively transferred to nonimmune mice with the T-cell fraction of spleen cells. These results indicate that both molecular size and dose are critical determinants for eliciting opsonic killing antibody to mucoid P. aeruginosa after immunizing with MEP.

摘要

先前的研究表明,抗铜绿假单胞菌黏液样胞外多糖(MEP)抗体可根据其功能活性分为两类。一类能够与白细胞和补体共同介导调理吞噬杀伤作用,另一类则不能。我们在小鼠中研究了与诱导调理吞噬杀伤抗体相关的这种抗原的特性。我们发现,已作为人用疫苗进行测试的较小尺寸物质(洗脱体积Kav = 0.26),在低剂量(1至10微克)时能在小鼠中诱导调理吞噬杀伤抗体,而在剂量大于或等于40微克时,仅产生非调理吞噬杀伤抗体。热灭活的黏液样铜绿假单胞菌细胞也观察到类似的剂量效应。用高剂量的这种MEP或热灭活细胞免疫后,无论用何种剂量的MEP作为加强免疫,小鼠都难以诱导出调理吞噬杀伤抗体。相比之下,较大分子量的制剂(Kav = 0.05)在很宽的剂量范围内(1至400微克)都能诱导调理吞噬杀伤抗体。此外,50微克的较大尺寸制剂能够克服50微克较小物质所诱导的抑制作用。50微克较小物质所诱导的抑制作用可通过脾细胞的T细胞部分过继转移至未免疫的小鼠。这些结果表明,在用MEP免疫后,分子大小和剂量都是诱导针对黏液样铜绿假单胞菌的调理吞噬杀伤抗体的关键决定因素。

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