沙眼衣原体生殖道感染免疫及疫苗研究进展

沙眼衣原体 (ｃｈｌａｍｙｄｉａｔｒａｃｈｏｍａｔｉｓ ,ＣＴ)是一种严格的细胞内寄生性微生物 ,是沙眼和性传播疾病的主要病原体 ;通过性接触传播 ,可引起男性尿道炎、附睾炎 ,女性宫颈炎、盆腔炎 ,还可继发不育和异位妊娠等 ,对人类健康构成极大危害[1] 。为了控制沙眼衣原体的感染 ,很多实验室从各个方面对沙眼衣原体做了大量的研究工作并取得了很大进展 ,包括在 1998年获得了沙眼衣原体基因组的全部序列。沙眼衣原体疫苗的发展可以预防沙眼衣原体所致性传播疾病 ,迄今已从多种途径探讨疫苗的研制 ,但尚无成熟疫苗问世。沙眼衣原体感染…     

生殖道沙眼衣原体(CT)感染与不孕不育

一、沙眼衣原体感染的机制 沙眼衣原体(CT)引起的泌尿生殖道感染,目前已成为许多国家和地区最为常见的性传播疾病,在全球8%～12%不育夫妇中,CT生殖道感染的急、慢性感染所造成的生殖道炎症、粘连与阻塞是引起不孕的主要原因.     

沙眼衣原体生殖道感染与机体的特异性保护性免疫应答

衣原体是一类独特的细菌,对人类及其他动物具有广泛的致病性。其中沙眼衣原体主要感染人类。沙眼衣原体D－K血清型引起的生殖道感染是最常见的细菌性性传播疾病之一。研究表明,机体对沙眼衣原体生殖道感染产生保护性的免疫应答。     

4212例泌尿生殖道感染沙眼衣原体PCR检测研究

４２１２ 例泌尿生殖道感染患者沙眼衣原体（ＣＴ） 行ＰＣＲ 检测，总阳性率２２－７９％ ；ＣＴ 阳性者中，合并１３ 项其他（ＮＧＨ、ＵＵ、ＨＰＶ）感染的占６８－７５％ ，ＣＴ 感染率男性（２２－８６ ％） 与女性（２２－７６％ ）十分相近，但合并感染率女性（７１－４３ ％ ）显著高于男性（６２－５ ％） ，Ｐ＜ ０－０１。本组结果显示，ＣＴ 主要通过性接触传染。     

沙眼衣原体生殖道感染与机体的特异性保护性免疫应答

衣原体是一类独特的细菌 ,对人及其他动物具有广泛的致病性。其中沙眼衣原体主要感染人类。沙眼衣原体D K血清型引起的生殖道感染是最常见的细菌性性传播疾病之一。研究表明 ,机体对沙眼衣原体生殖道感染产生保护性的免疫应答     

E-选择素在生殖道沙眼衣原体感染中的作用研究

目的 研究E-选择素在生殖道沙眼衣原体感染中的作用.方法 将64只小鼠生殖道沙眼衣原体感染模型随机分成2组,实验组中的小鼠用人工合成E-选择素干预,对照组中的小鼠用生理盐水进行干预,统计两组在1w,2w,3w,4w不同时间点上的感染小鼠阴道脱落菌量以及沙眼衣原体感染率.结果 成功建立生殖道沙眼衣原体感染的小鼠模型:与对照组相比较,人工合成E-选择素干预后1w和2w的生殖道沙眼衣原体感染率(90.2％vs 77.4％,85.3％vs 70.1％)显著增高,而阴道脱落菌量显著增高(4.758 ±0.225 vs 3.210 ±0.315,2.698±0.177 vs 1.809±0.203),两组间差异具有统计学.在干预后3w两组的沙眼衣原体感染率分别为34％和24％,阴道脱落菌量分别为1.412±0.134和1.201±0.189,两组间差异无统计学意义;两组在干预后4w的沙眼衣原体感染率均为0且无阴道脱落菌量.结论 E-选择素能促进生殖道沙眼衣原体感染的发生率以及增加沙眼衣原体的毒力,本文为进一步阐明生殖道沙眼衣原体感染的发病机制提供实验依据.     

096 沙眼衣原体生殖道感染与机体的特异性保护性免疫应答

衣原体是一类独特的细菌,对人及其他动物具有广泛的致病性.其中沙眼衣原体主要感染人类.沙眼衣原体D-K血清型引起的生殖道感染是最常见的细菌性性传播疾病之一.研究表明,机体对沙眼衣原体生殖道感染产生保护性的免疫应答.     

三种不同药物治疗女性沙眼衣原体泌尿生殖道感染疗效观察

目的 对照观察美满霉素、阿奇霉素、加替沙星治疗沙眼衣原体所致的女性泌尿生殖道感染的疗效。方法 A组给予口服美满霉素100mg，每日2次，疗程2周；B组静脉点滴乳糖酸阿奇霉素500mg，每日1次，疗程10d；C组静脉点滴加替沙星400rag，每日1次，疗程10d。结果 A组有效率63．46％，B组有效率82．35％，C组有效率93．24％，三组有效率比较有非常显著差异性（X^2=17．96P〈0．005），不良反应发生率A（15．38％）组高于B（7.35％）、C（8．10％）两组。结论 静脉给予阿奇霉素组与加替沙星组疗效好于口服美满霉素组，阿奇霉素与加替沙星均有较好的疗效，但加替沙星的疗效更为显著，可作为治疗沙眼衣原体性泌尿生殖道感染的首选药物。     

生殖道沙眼衣原体感染与自然流产的关系

目的探讨沙眼衣原体（CT）与自然流产的关系。方法对67例（自然流产组）和52例人工流产及正常妊娠中期妇女（对照组）的宫颈粘液，及9例自然流产组和27例人工流产妇女的流产胚胎组织进行CT检测。结果自然流产组的宫腔粘液和流产胚胎组织中CT阳性率均明显高于时照组，两组比较差异有显著性（P＜0．01），且随着自然流产次数的增加，CT阳性率又逐步增高的趋势（P＜0．05）。结论生殖系统CT感染与部分自然流产关系密切，宫内CT感染可侵入胚胎，影响胚胎发育，导致流产。     

金标法检测514例生殖道感染妇女宫颈分泌物中沙眼衣原体抗原

目的了解育龄妇女宫颈分泌物标本中沙眼衣原体抗原阳性率。方法用金标法对2004年1月至2005年9月间拟诊为生殖道感染的年龄在23~40岁之间的育龄妇女宫颈分泌物标本检测沙眼衣原体抗原。结果514例拟诊为生殖道感染的育龄妇女生殖道标本中126例为沙眼衣原体抗原阳性,阳性率为24.5%,高于对照组(8.0%),经统计学处理,二者间有高度显著性差异(P<0.005)。结论育龄妇女生殖遒感染与沙眼衣原体有关,育龄妇女沙眼衣原体感染率较高,因孕期感染沙眼衣原体可引起母婴传播,所以应孕前、孕期及产前应常规检测沙眼衣原体,并且最好同时检测解脲支原体和淋球菌。这对优生工作有重要意义。     

Relationship between an asymptomatic male genital tract exposure to Chlamydia trachomatis and an autoimmune response to spermatozoa

The relationship between a localized genital tract humoral immuneresponse to Chlamydia trachomatis and the presence of antispermantibodies on the surface of motile spermatozoa in the ejaculatewas examined in 227 asymptomatic male partners of infertilecouples with no history of exposure to C.trachomatis. Semenand serum samples were assayed for immunoglobulin (Ig) A andIgG antibodies to C.trachomatis by enzyme-linked immunosorbentassay employing a recombinant Chlamydia-specific lipopolysaccharidefragment (Medac, Hamburg, Germany), while motile spermatozoawere tested for bound autoantibodies by immunobead binding.Semen samples from 24.7 and 10.9% of the men were positive forIgA and IgG antibodies to C.trachomatis respectively. In comparison,antichlamydial IgA was less prevalent in sera (14.5%) than insemen (P = 0.01), while antichlamydial IgG was most prevalent(21.5%) in sera (P =0.003). In 75.0% of the men with antichlamydialIgA in their semen, this antibody was undetectable in sera obtainedat the time of semen collection. Conversely, 84.0% of the menwith seminal antichlamydial IgG were also IgG seropositive.Antisperm IgG and/or IgA were detected on motile spermatozoafrom 16.3% of the men; their occurrence was strongly correlatedwith the presence of antichlamydial IgA in semen (P < 0.0001).Weaker associations between antisperm antibodies and eitherseminal IgG antibodies to C.trachomatis (P = 0.01) or circulatingIgA and IgG antichlamydial antibodies (P = 0.03) were also observed.Men with antichlamydial IgA in their semen had a lower mediansperm count (82 versus 144 x 10⁶/ml) than those men without(P = 0.003); sperm morphology and motility were comparable inboth groups. These data suggest that asymptomatic male genitaltract exposure to C.trachomatis is a frequent event among thispopulation and that the presence of a humoral immune responseto this organism is correlated with the development of an autoimmuneresponse to spermatozoa.     

Chlamydia trachomatis: time for screening?

Genital Chlamydia trachomatis infection is the leading cause of bacterial sexually transmitted disease in industrialised countries, particularly among young people. The consequences of chlamydial infection may involve urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, epididymitis and prostatitis. In addition, chlamydial infection increases the risk of acquisition of human immunodeficiency virus and has been associated with cervical cancer. Although screening programmes exist in a number of countries, the continuously increasing prevalence of chlamydial infections demonstrates the necessity for health authorities to establish effective screening policies, and the importance of defining a comprehensive European screening policy is emerging.     

Detection of Chlamydia trachomatis in Papanicolaou-stained cervical smears: control study by in situ hybridization

Ninety-one Papanicolaou-stained vaginopancervical smears were destained and subjected to in situ hybridization with Chlamydia trachomatis DNA probe. At cytologic examination (Pap test), 71 smears showed changes suggestive of chlamydial infection, while remaining 20 were negative. At the control by in situ hybridization, the results of Pap test were confirmed in 85 out of 91 cases, two false-positive and four false-negative cases being detected. The sensitivity and specificity of Pap test, compared with in situ hybridization, were 95% and 89%, respectively. Like some recent reports, the present study confirms the reliability of Pap test in the detection of Chlamydia trachomatis and its possible relevant role in reducing the diffusion of the infection, when properly applied to mass-screening program.     

Immune response in mice infected in the genital tract with mouse pneumonitis agent (Chlamydia trachomatis biovar).

Female Swiss-Webster mice were inoculated intravaginally with mouse pneumonitis agent (MoPn), a Chlamydia trachomatis biovar. Inoculation with 3.5 X 10(5) egg lethal doses per mouse resulted in shedding of the agent from the genital tract for as long as 21 days. Immunoglobulin M antibodies to MoPn were detected in plasma by day 7 post-inoculation, and immunoglobulin G antibodies were detected by day 14. Antibodies were detected in genital secretions by day 20, and titers in plasma and secretions were still considerable on day 56. Delayed-type hypersensitivity tests, determined by footpad swelling, were not positive in appreciable numbers of animals until after day 25. Delayed-type hypersensitivity reactions were maximal 24 h after testing and were preceded by an Arthus-like reaction, which appeared within 3 h and declined by 12 h. Convalescent animals were rechallenged by intravaginal inoculation and were found to be solidly immune.     

拟诊为淋病患者中泌尿生殖道沙眼衣原体基因分型及序列分析

目的 了解深圳市拟诊为淋病患者中泌尿生殖道沙眼衣原体的合并感染情况及其基因型分布和序列变异特点.方法 采集401例拟诊为淋病患者的泌尿生殖道分泌物样本,应用Roche Amplicor全自动核酸检测系统对样本进行淋球菌和沙眼衣原体双检,提取DNA,应用巢式聚合酶链反应(nested-PGR)扩增沙眼衣原体主要外膜蛋白基因(omp1)中的VS1～VS2片段,并对其进行序列测定,所获得的序列利用Mega4.0软件与标准参考株进行比对,分析确定其基因型及序列变异情况.结果 401例拟诊为淋病患者中淋球菌的感染率为82.3%(330/401),沙眼衣原体的感染率为24.2%(97/401),淋球菌和沙眼衣原体的合并感染率为21.7%(87/401).97份沙眼衣原体阳性样本中获得73份沙眼衣原体基因片段序列,共检出8个基因型,分别为E型(27.4%)、G/Ga型(23.3%)、D/Da型(16.4%)、F型(13.7%)、J型(11.0%)、H型(5.5%)、B和K型(各1.4%).序列分析发现3例(4.1%)菌株发生错义突变,分别为D/Da型、E型、G/Ga型;F型、H型、J型和K型序列虽多见碱基突变,但均为同义突变.结论淋病患者合并感染沙眼衣原体的比例较高,且泌尿生殖道沙眼衣原体的基因型以E、G/Ga、D/Da和F型为主.序列分析可以为泌尿生殖道沙眼衣原体的分子流行病学研究提供依据.     

Surfactant protein D is present in the human female reproductive tract and inhibits Chlamydia trachomatis infection

Surfactant protein D (SP-D) is a lung collectin involved in innate host defence mechanisms in the lung. SP-D is also expressed at other mucosal sites throughout the human body. In the present study, we show that SP-D mRNA and protein are expressed in the human female reproductive tract. SP-D protein was localized in the apical portion of the reproductive epithelial cells. We also demonstrate that endometrial and endocervical cell lines and primary endocervical cells in culture produce SP-D mRNA and protein. Chlamydia trachomatis is an intracellular pathogen that infects the female reproductive tract, primarily the cervix, and is responsible for the most prevalent infectious disease in the USA. Untreated chlamydial infections of the female reproductive tract often result in sterility of the infected woman. Since SP-D protein is produced in cervical glands, we examined the effect of SP-D on chlamydial infection of cervical epithelial cells in vitro. We found that SP-D protein inhibits the infection of HeLa cells (an endocervical epithelial cell line) by C. trachomatis in a dose-dependent manner. We further demonstrate that the SP-D lectin-binding domain is involved in inhibiting infection of HeLa cells by Chlamydia. In conclusion, we detected SP-D in the female reproductive tract and determined that one of the functions of the SP-D protein may be to protect cervical epithelial cells from infection by C. trachomatis.     

Mucosal and peripheral immune responses to chlamydial heat shock proteins in women infected with Chlamydia trachomatis

Most of the studies on 60-kDa and 10-kDa chlamydial heat shock proteins (HSPs) to date have been carried out with blood lymphocytes or serum antibody responses, which do not provide a clear picture of the actual pathogenesis as they do not differentiate primary infection from recurrent infection. Thus, in the present study induction of the immune response was evaluated by studying lymphoproliferation of both cervical and peripheral lymphocytes to synthetic peptides of cHSP60, cHSP10 and major outer membrane protein (MOMP) antigen. In addition, cervical antibody prevalence to MOMP antigen, cHSP60 and cHSP10 and cytokine levels in cervical washes was also determined. Positive proliferative responses of cervical lymphocytes to cHSP10 peptide were significantly higher (P < 0.05) in women with recurrent infections and that to MOMP antigen were significantly higher in primary infection. On proliferation of PBMCs with the above antigens, no significant difference was observed between primary and recurrent infection. Prevalence of cervical IgG and IgA antibodies to Chlamydia trachomatis was significantly higher (P < 0.05) during primary infection than recurrent infections. In contrast, prevalence of IgG and IgA antibodies to cHSP10 and IgG antibodies to cHSP60 was higher during recurrent infections than primary infections. Interferon (IFN)-gamma levels were significantly higher in cervical washes of women with recurrent infection and correlated strongly with cHSP60 antibody titres. Our data thus suggest that mucosal responses are more appropriate in understanding the pathogenesis of chlamydial infection and IFN-gamma could be involved in the modulation of immune responses towards chlamydial infection directly, by causing acute inflammation, or indirectly through modulation of HSP expression.     

An experimental model for salpingitis due to Chlamydia trachomatis and residual tubal infertility in the mouse

A mouse model of salpingitis and subsequent tubal infertility induced by a human strain of Chlamydia trachomatis has been studied. C3H/He female mice were inoculated into the ovarian bursa. Some of the mice (six infected, five controls) were killed on days 15 and 23 and the remaining animals (10 infected, 10 controls) were mated on day 15. On day 15, the infection was maximal with intratubal inflammation, elevated antichlamydial antibody titre and positive cultures in 12 cases out of 16. After 19 weeks of housing with the male, the proportion of fertilized females was significantly lower in the infected group (20% versus 100% in the control group P less than 0.01). In the killed mice, hydrosalpinx and or tubal occlusion were noted at this time in nine cases out of 10, despite an apparent bacteriological healing.     

E-选择素、CD14及VCAM1水平与生殖道沙眼衣原体感染的相关性分析

目的 探讨E-选择素、CD14及血管细胞粘附分子(vascular cell adhesion molecule 1,VCAM1)水平与生殖道沙眼衣原体感染的相关性.方法 选取86例生殖道沙眼衣原体感染患者为观察组;根据生殖道沙眼衣原体感染患者是否伴有炎症,分为感染伴炎症组和感染无炎症组,各43例;同时,选取36例健康体检者为对照组;采用双抗体夹心酶联免疫吸附法(ELISA)测定所有研究对象的血清E-选择素、CD14及VCAM1水平,并作对比分析;观察组患者采取炎克宁冲剂结合阿奇霉素治疗,对比治疗前后的血清E-选择素、CD14及VCAM1水平,并与对照组作对比分析.结果 观察组的血清E-选择素、CD14及VCAM1水平均显著高于对照组;差异具有统计学意义(P＜0.05);感染伴炎症组与感染无炎症组的血清E-选择素、CD14及VCAM1水平的差异具有统计学意义(P＜0.05);观察组患者采取炎克宁冲剂结合阿奇霉素治疗后,临床总有效率为94.19％,生殖道沙眼衣原体转阴率为87.21％;治疗后的血清E-选择素、CD14及VCAM1水平显著低于治疗前水平,差异具有统计学意义(P＜0.05);与对照组对比,差异无统计学意义(P＞0.05).结论 生殖道沙眼衣原体感染的病情进展与E-选择素、CD14及VCAM1水平密切相关,通过监测E-选择素、CD14及VCAM1水平,可为生殖道沙眼衣原体感染的治疗、评估疗效及预后而提供依据.