梅毒免疫研究进展

梅毒是由梅毒螺旋体感染引起的一种性传播疾病,主要通过黏膜或受伤的皮肤传播,其临床表现复杂多样,几乎可侵犯全身各器官。机体对于梅毒螺旋体的免疫应答过程十分复杂,固有免疫、细胞免疫及体液免疫均参与该过程。梅毒螺旋体免疫逃逸机制尚未明确。梅毒螺旋体免疫应答及免疫逃逸机制的研究,可为梅毒发病机制的进一步明确及疫苗的研制奠定基础。本文综述梅毒免疫以上几个方面的研究进展。     

梅毒、淋病和生殖道沙眼衣原体感染诊疗指南（2020年）

梅毒、淋病和生殖道沙眼衣原体感染是我国目前重点防治的性传播疾病。梅毒的临床表现复杂,按照其发病时间、临床表现及传染方式,可分为一期梅毒、二期梅毒、三期梅毒、神经梅毒、隐性梅毒及先天梅毒等。淋病和生殖道沙眼衣原体感染主要侵犯泌尿生殖道,其临床表现从无症状到伴发各种并发症,差别较大。这3种性病的诊断应依据流行病学史、临床表现及实验室检查结果综合判断后确定。应尽早、规范并按推荐方案进行治疗。治疗后应进行必要的随访。淋病的病原体耐药已经成为临床关注的问题。     

Cell-mediated immunity during syphilis. A review

Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types.     

梅毒及其与HIV合并感染的免疫机制研究

梅毒不同的临床表现多取决于细胞免疫的强度和持续时间,巨噬细胞、CD4+T淋巴细胞、CD8+T淋巴细胞、自然杀伤细胞均在梅毒感染的细胞免疫中起重要作用.而与HIV合并感染更是增加了其免疫机制的复杂性和临床表现的多形性.在与HIV合并感染的二期梅毒中,Th1、Th17型细胞免疫增强,而Th2型细胞免疫的改变目前尚不确切.梅毒与HIV合并感染时两者的免疫机制、病程以及疗效均可能发生影响,因此,有必要进行梅毒患者的HIV筛查和HIV感染者的梅毒筛查,以便获得及时有效的治疗.     

Benign tertiary syphilis

Benign tertiary syphilis (BTS) includes all forms of symptomatic acquired syphilis occurring beyond the secondary and relapsing stages, with the exception of cardiovascular and neurosyphilis.^1–5 This group of manifestations is sometimes also called “late benign syphilis.” The characteristic lesion is the gumma, and generally speaking, the longer the interval between initial infection and lesion onset, the more destructive the manifestations will be.The incidence of BTS in untreated cases is set at 16.6% in the Gjestland revision of the Bruusgaard figures, but the incidence in the general population has been steadily falling in the past 50 years, and BTS in any form has become a rare disease. Experience at the Vanderbilt clinic, for example, showed a decline in the average number of cases per five-year period from 130 in 1940 to 17 in 1951.⁵ No doubt it is significantly lower now.With classically accepted exceptions—the ovary, for example, and the small intestine—BTS can affect virtually any anatomic site. The great majority of lesions are concentrated in the skin, mucous membranes, and bone, however; and the material presented in this section will deal principally with disease in those structures. The distribution of BTS by site in the series of 601 examples collected by Kampmeier6 is shown in Table 13-1.BTS lesions can appear as early as two years and as late as 35 years after the initial infection. The great majority of cases fall in the 2-to 7-year time period.     

Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study

BACKGROUND: Despite reports of unusual clinical presentations and therapeutic responses among HIV-infected patients with syphilis, syphilis has not been regarded as a serious opportunistic infection that predictably progresses among most HIV-coinfected patients. GOAL: To define and describe differences in the presentation and response to treatment of early syphilis among HIV-infected and HIV-uninfected patients, to describe any differences by gender, and to determine if clinical presentation of central nervous system involvement predicted serologic failure. DESIGN: A prospective, multicenter, randomized, controlled trial of enhanced versus standard therapy to compare the benefit of enhanced therapy, the clinical importance of central nervous system involvement, and the clinical manifestations of early syphilis infection among HIV-infected and HIV-uninfected patients. RESULTS: The median number of ulcers was significantly greater among HIV-infected and HIV-uninfected patients, as was the percent of HIV-infected patients with multiple ulcers. Among patients diagnosed with secondary syphilis, a higher percentage of HIV-infected patients presented with genital ulcers [13/53 (25%)] than did HIV-uninfected patients [27/200 (14%)]. No differences between HIV-infected and HIV-uninfected patients were detected for other secondary syphilis manifestations. Although women presented more frequently with secondary syphilis than did men, no other gender differences in clinical manifestations were noted. Neurologic complaints were reported most frequently among patients with secondary syphilis [103/248 patients (42%)] compared with patients with primary syphilis [32/136 (24%)] and early latent syphilis [48/ 142, (34%)] (P < 0.05), but no differences in neurologic complaints were apparent by HIV status or CSF abnormalities. No neurologic complaints were significantly associated with serologic treatment failures at 6 months. CONCLUSIONS: Overall, HIV infection had a small effect on the clinical manifestations of primary and secondary syphilis. Compared with HIV-uninfected patients, HIV-infected patients with primary syphilis tended to present more frequently with multiple ulcers, and HIV-infected patients with secondary syphilis presented with concomitant genitals ulcers more frequently.     

Immunologic mechanisms of infectious syphilis.

We believe that humoral and cellular immunity both are involved in the response of the host to infection with T. pallidum. A complex interaction between stimulation and suppression of cell-mediated immunity may be involved. This interaction may explain the unusual clinical course in which secondary syphilis waxes and wanes before culminating in immunity.     

妊娠梅毒与胎传梅毒

近年来妊娠梅毒和胎传梅毒的发病率呈上升趋势。感染梅毒螺旋体后，由于免疫反应及细胞因子水平随病期的进展而变化，导致不同的妊娠结局，包括胚胎死亡、流产、早产或娩出胎传梅毒患儿；妊娠期间机体免疫反应状态的改变也会影响母体及胎传梅毒的自然病程。因此，进一步了解妊娠与梅毒的相互影响，揭示妊娠梅毒和胎传梅毒发生发展的规律，对于有效地控制梅毒的母婴传播，预防梅毒导致的不良妊娠结局，降低胎传梅毒的发病率具有重要意义。     

梅毒免疫学机制研究进展

在梅毒螺旋体感染的不同病期,细胞免疫和体液免疫均有部分涉及,目前认为主要与T细胞介导的免疫反应有关,血清抗体仅有部分保护作用,同时还存在不同程度的免疫抑制现象。梅毒早期出现的体液免疫和细胞免疫对梅毒螺旋体的清除起重要作用,而在晚期出现的细胞免疫反应则主要引起组织损害。本文就近年来关于梅毒螺旋体的免疫原性、感染梅毒后机体的免疫反应以及梅毒螺旋体免疫逃逸等方面的研究进展作一综述。     

Rapid progression to gummatous tertiary syphilis in a patient with HIV

Co-infection with human immunodeficiency virus-1 (HIV) and syphilis is associated with rapid progression to tertiary syphilis. This case report describes the early development of gummatous skin disease and suspected neurosyphilis in a patient with untreated HIV and approaches to treatment.     

Immunoregulatory properties of serum from patients with different stages of syphilis

The response of lymphocytes from 17 patients with primary, secondary, and tertiary syphilis to phytohaemagglutinin (PHA) and to allogeneic lymphocytes was normal in heterologous serum; however, the responsiveness of cells from some patients with primary and secondary disease was significantly reduced in the presence of autologous serum. As cells from healthy controls invariably responded better to these stimuli in autologous serum, the sera from 81 patients with syphilis were screened for immunosuppressive properties. Sera from 25 primary, 32 secondary, two tertiary, six congenital, and 16 latent cases of syphilis were examined for their ability to reduce the responsiveness of normal cells to PHA. These experiments were performed with test sera as the sole source of serum for the cultures or with test sera added to cultures containing optimally supportive amounts of pooled human plasma.

Stimulation of normal cells from one control in human plasma and 20% test serum showed that only in sera from congenital cases of syphilis was the mean response significantly different from the response seen in control sera; a significant increase in the response to stimulation occurred. The range of response to PHA with sera from cases of primary and secondary syphilis was wider than with normal sera. Sera from five (20%) cases of primary and 14 (44%) cases of secondary syphilis appeared to be immunosuppressive. When retested on another sample of normal cells, these sera were consistently immunosuppressive even in the presence of 15% pooled human plasma. Thus, in early syphilis antigenic stimulation may result in the release from suppressor cells of non-specific immunoregulators of cell-mediated immunity. Such phenomena may be a prelude to the development of tolerance to treponemal antigens. In congenital syphilis the development of suppressor cells may be impaired, resulting in the apparent immunostimulatory properties of serum from such cases.

     

The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis

Syphilis is a well‐known sexually transmitted infection infamous for its protean cutaneous manifestations. Over the last decade, the rate of infection in the USA has risen, particularly among human immunodeficiency virus (HIV)‐infected individuals and certain ethnic groups. Although the primary chancre developing at the site of inoculation usually has typical and well‐characterized features, cutaneous manifestations of secondary syphilis span a wide spectrum and mimic those of other dermatoses. This may be particularly evident in patients with HIV. Such deviations from the expected typical papulosquamous eruption may present a diagnostic challenge and delay diagnosis and therapy. Given the increasing incidence of syphilis among the immunosuppressed patient population, recognition of atypical cutaneous manifestations is critical for adequate management. We review a range of cutaneous manifestations of secondary syphilis and the skin diseases it may mimic.     

细胞因子与梅毒免疫学研究进展

梅毒是由梅毒螺旋体引起的一种系统性的性传播疾病.感染梅毒后,机体对梅毒的免疫学反应复杂,多种细胞因子在梅毒的发病及病情进展中起重要作用.在梅毒早期,Th1型细胞因子介导的细胞免疫反应占优势,以利于机体清除梅毒螺旋体;随着病情进展,Th2型细胞因子介导的体液免疫反应逐渐增强,导致梅毒螺旋体的免疫逃逸.概述Th1型、Th2型、Th17型等7种细胞因子及一些趋化因子在梅毒发病过程中的作用.     

The many faces of secondary syphilis: a re-emergence of an old disease

There has been a recent dramatic re-emergence of syphilis in the UK. This article describes the varied clinical manifestations of secondary syphilis and describes the diagnosis and current guidelines for treatment, especially in association with human immunodeficiency virus infection.     

梅毒免疫和梅毒螺旋体的研究进展

梅毒螺旋体有着独特的基因和蛋白结构,对其基因分型有利于梅毒分子流行病学的研究.梅毒螺旋体缺乏脂多糖与外膜蛋白,但可表达多种脂蛋白,这些脂蛋白同梅毒螺旋体的组织黏附及播散有关,同时可诱导机体发生免疫应答.机体对于梅毒螺旋体的免疫应答过程十分复杂,固有免疫、体液免疫及细胞免疫均在梅毒螺旋体的感染过程中参与了应答过程.Th1型细胞免疫在梅毒的发生发展过程中起重要作用,梅毒患者在局部及系统免疫方面都存在细胞免疫的异常.     

Malignant syphilis in an HIV-infected patient

Patients with HIV infection may develop common diseases with atypical clinical features. HIV infection may change the classic clinical course of syphilis and increase the incidence of a subtype of secondary syphilis named malignant syphilis. A homosexual patient with HIV infection consulted us about a one-month history of general malaise and widespread cutaneous ulcerative lesions, some with thick hemorrhagic crusts. Serology for syphilis was positive at high titers. Based on clinical, histological and serological findings, a diagnosis of malignant syphilis was made and the patient started treatment with penicillin G benzathine with progressive resolution of lesions. Malignant syphilis is a rare subtype of secondary syphilis that presents special clinical and histological features and has been associated with several processes characterized by variable degrees of immunosuppression. It is necessary to take into account this entity among the possible diagnoses in HIV-infected patients with cutaneous lesions.     

关于当前梅毒诊治中的几个问题探讨

梅毒的传染力强,危害性大,与HIV又相互协同,已成为重大的公共卫生问题和社会问题之一。我国梅毒2006年上报病例数首次超过淋病,2007年全国梅毒报病225601例,较2006年上升21．19％,尤其是潜伏梅毒和胎传梅毒发病率直线上升,应引起临床各科医生的重视。为减少误诊误治,本文就当前梅毒的临床表现多样性提出探讨,梅毒的高峰期已经来了,在艾滋病经性传播日趋严重的情况下,提示控制性病来控制艾滋病,控制胎传梅毒作为消除梅毒的步骤之一。     

Human immunodeficiency virus and leprosy: an update

Coinfection with human immunodeficiency virus (HIV) has a major effect on the natural history of many infectious diseases, particularly mycobacterial diseases. Early in the HIV epidemic, it was predicted that HIV infection would worsen leprosy outcomes, with more patients developing lepromatous disease, an impaired response to multidrug therapy and fewer reactions. However, studies on the epidemiologic and clinical aspects of leprosy suggest that the course of leprosy in coinfected patients has not been greatly altered by HIV. In contrast, initiation of antiretroviral treatment has been reported to be associated with activation of subclinical Mycobacterium leprae infection and exacerbation of existing leprosy lesions. With regular new discoveries about the interaction of leprosy and HIV, the need to maintain research in this field is of considerable importance.     

梅毒母婴传播的研究进展

母婴传播是梅毒传播的重要途径,妊娠任何时期都可能发生梅毒的母婴传播.梅毒的母婴传播可以导致许多不良的妊娠后果,严重影响母婴健康,是一项严重的公共卫生和社会问题.梅毒的母婴传播与孕妇梅毒的分期、妊娠时期及是否治疗有关,特别是早期梅毒的母婴传播风险较高.随着梅毒发病率的增长,梅毒母婴传播的防控变得愈加重要,妊娠期梅毒的筛查和早期治疗可有效的阻断梅毒母婴传播.因此,了解梅毒母婴传播的流行病学、传播途径与传播风险及其影响因素等无疑会对其防控提供一个较好的指导途径.