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铜绿假单胞菌表面多糖疫苗。基础研究的新治疗方法。

Pseudomonas aeruginosa surface polysaccharide vaccines. New therapeutic approaches from basic research.

作者信息

Pier G B

出版信息

Antibiot Chemother (1971). 1985;36:157-67.

PMID:3923913
Abstract

Surface polysaccharide antigens, expressed by strains of P. aeruginosa, are readily available for interaction with the host immune systems. These interactions could potentially result in development of protective immunity against P. aeruginosa infections. Classic strains of P. aeruginosa isolated from immunocompromised hosts and the environment generally express cell surface LPS antigens containing the serotype determinant. Antibody to these determinants has clearly been shown to be protective in both animals and humans. Immunization with a nontoxic, high molecular weight polysaccharide fraction, obtained from the culture supernate of P. aeruginosa, results in the induction of high titered, functional antibody against the type specific determinant. In addition, experimental protocols in animals have shown that a T cell-mediated immunity against type specific antigens can also provide protective immunity. Although the role of T cell-mediated immunity in protection against P. aeruginosa infections is unclear, it may be important in augmenting antibody-mediated protection. P. aeruginosa isolates from CF patients generally do not express type-specific antigens. They do, however, express a different cell surface polysaccharide, MEP. Antibody to this material is made by the colonized CF host, but it clearly is not associated with protective immunity. Animal antibody raised to this material is able to mediate opsonic killing of mucoid strains of P. aeruginosa. Therefore, the antibody response to MEP made by the CF patients may be non-opsonic, or if opsonic, may indicate that antibody to this antigen is not protective in CF patients. Antibody to MEP is able to interact with a low level of human complement for opsonic killing, suggesting that this antibody may be of use in the lung of the CF patient, where complement components may be either low or inactive.

摘要

铜绿假单胞菌菌株表达的表面多糖抗原易于与宿主免疫系统相互作用。这些相互作用可能会引发针对铜绿假单胞菌感染的保护性免疫。从免疫功能低下宿主和环境中分离出的经典铜绿假单胞菌菌株通常表达含有血清型决定簇的细胞表面脂多糖抗原。针对这些决定簇的抗体已明确显示在动物和人类中均具有保护作用。用从铜绿假单胞菌培养上清液中获得的无毒高分子量多糖组分进行免疫,可诱导产生针对型特异性决定簇的高滴度功能性抗体。此外,动物实验方案表明,针对型特异性抗原的T细胞介导免疫也可提供保护性免疫。尽管T细胞介导免疫在预防铜绿假单胞菌感染中的作用尚不清楚,但它可能在增强抗体介导的保护作用中很重要。来自囊性纤维化(CF)患者的铜绿假单胞菌分离株通常不表达型特异性抗原。然而,它们确实表达一种不同的细胞表面多糖,即MEP。定居的CF宿主会产生针对这种物质的抗体,但显然这与保护性免疫无关。针对这种物质产生的动物抗体能够介导对铜绿假单胞菌黏液型菌株的调理吞噬杀伤作用。因此,CF患者对MEP产生的抗体反应可能是非调理吞噬性的,或者即使是调理吞噬性的,也可能表明针对该抗原的抗体在CF患者中没有保护作用。针对MEP的抗体能够与低水平的人补体相互作用以进行调理吞噬杀伤,这表明这种抗体可能在CF患者的肺部发挥作用,因为肺部的补体成分可能含量低或无活性。

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Pseudomonas aeruginosa surface polysaccharide vaccines. New therapeutic approaches from basic research.铜绿假单胞菌表面多糖疫苗。基础研究的新治疗方法。
Antibiot Chemother (1971). 1985;36:157-67.
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Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients.在体外生物膜中生长的黏液型铜绿假单胞菌可被针对黏液型胞外多糖荚膜的调理素抗体杀死,但囊性纤维化患者慢性肺部感染期间产生的抗体则不能将其杀死。
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Immune complexes from immunized mice and infected cystic fibrosis patients mediate murine and human T cell killing of hybridomas producing protective, opsonic antibody to Pseudomonas aeruginosa.来自免疫小鼠和感染囊性纤维化患者的免疫复合物介导了对产生针对铜绿假单胞菌的保护性调理素抗体的杂交瘤的鼠源和人源T细胞杀伤作用。
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Biologic activities of antibodies to the neutral-polysaccharide component of the Pseudomonas aeruginosa lipopolysaccharide are blocked by O side chains and mucoid exopolysaccharide (alginate).铜绿假单胞菌脂多糖中性多糖成分的抗体生物活性被O侧链和黏液样胞外多糖(藻酸盐)阻断。
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Complement deposition by antibodies to Pseudomonas aeruginosa mucoid exopolysaccharide (MEP) and by non-MEP specific opsonins.由抗铜绿假单胞菌黏液样胞外多糖(MEP)抗体以及非MEP特异性调理素介导的补体沉积。
J Immunol. 1991 Sep 15;147(6):1869-76.
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Nonspecific immunoglobulin synthesis and elevated IgG levels in rabbits immunized with mucoid exopolysaccharide from cystic fibrosis isolates of Pseudomonas aeruginosa.用来自铜绿假单胞菌囊性纤维化分离株的黏液样胞外多糖免疫的兔子中,非特异性免疫球蛋白合成及IgG水平升高。
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Cross-sectional and longitudinal studies of naturally occurring antibodies to Pseudomonas aeruginosa in cystic fibrosis indicate absence of antibody-mediated protection and decline in opsonic quality after infection.对囊性纤维化患者体内抗铜绿假单胞菌天然抗体的横断面研究和纵向研究表明,抗体介导的保护作用不存在,且感染后调理素质量下降。
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