Wallace F J, Witt C S, Clancy R L, Cripps A W
Faculty of Medicine, University of Newcastle, New South Wales, Australia.
Immunol Cell Biol. 1995 Jun;73(3):258-65. doi: 10.1038/icb.1995.42.
Rats intestinally immunized with whole killed non-typable Haemophilus influenzae clear this organism from the lungs faster than non-immunized rats. This study investigated the role of antibody and phagocytes in the clearance mechanism. First, dose-response experiments demonstrated that while lowering the dose of non-typable H. influenzae reduced the level of detectable specific antibody in bronchial washings, the ability to accelerate bacterial clearance persisted to much lower doses. Second, specificity experiments showed that intestinal immunization with non-typable H. influenzae cross-protected against Pseudomonas aeruginosa, even though antibodies were not absorbed out of serum by incubation with P. aeruginosa. Third, serum antibody was shown to be bactericidal for non-typable H. influenzae in the presence of complement (P < 0.05), while bronchial washings antibody was not. The bactericidal effect of the serum was abrogated by the addition of bronchial washings. Fourth, an ELISA quenching assay demonstrated that neutrophils from intestinally immunized rats were able to phagocytose more bacteria in a given time period (P < 0.05) than unimmunized rats and rats immunized by other routes. In the fifth experiment, the chemotactic response of neutrophils to casein was shown to be significantly depressed by the addition of bronchial washings obtained from immunized rats (P < 0.01). It is proposed that specific antibody in bronchial washings does not have a direct role in opsonizing bacteria for killing or phagocytosis, but instead has an anti-inflammatory effect. Non-specific effectors such as neutrophils driven by specific immune cells are a likely means of clearance of bacteria following intestinal immunization and acute challenge.
用全灭活不可分型流感嗜血杆菌进行肠道免疫的大鼠,比未免疫的大鼠能更快地从肺部清除这种细菌。本研究调查了抗体和吞噬细胞在清除机制中的作用。首先,剂量反应实验表明,虽然降低不可分型流感嗜血杆菌的剂量会降低支气管灌洗中可检测到的特异性抗体水平,但加速细菌清除的能力在低得多的剂量下仍持续存在。其次,特异性实验表明,用不可分型流感嗜血杆菌进行肠道免疫可对铜绿假单胞菌产生交叉保护,尽管抗体与铜绿假单胞菌孵育后不会从血清中被吸收。第三,血清抗体在补体存在的情况下对不可分型流感嗜血杆菌具有杀菌作用(P<0.05),而支气管灌洗抗体则没有。加入支气管灌洗后,血清的杀菌作用被消除。第四,酶联免疫吸附试验淬灭分析表明,与未免疫的大鼠和通过其他途径免疫的大鼠相比,肠道免疫大鼠的中性粒细胞在给定时间段内能够吞噬更多细菌(P<0.05)。在第五个实验中,加入从免疫大鼠获得的支气管灌洗后,中性粒细胞对酪蛋白的趋化反应被显著抑制(P<0.01)。有人提出,支气管灌洗中的特异性抗体在调理细菌以供杀伤或吞噬方面没有直接作用,而是具有抗炎作用。由特异性免疫细胞驱动的中性粒细胞等非特异性效应细胞可能是肠道免疫和急性攻击后清除细菌的一种方式。