人乳头瘤病毒多重感染与宫颈癌前病变及宫颈癌关系的研究进展

高危型人乳头瘤病毒(HPV)持续感染增加宫颈发生癌前病变及癌变的风险。因不同型别HPV的致病性不一致,所以宫颈感染不同型别的HPV后其病变的发生、发展及预后不同。由于HPV不同亚型间没有交叉抗体,HPV多重感染普遍存在。目前关于HPV多重感染是否会增加宫颈的患病率尚无定论,对宫颈癌前病变及宫颈癌的影响尚无一致意见。本文结合近年发表的国内外文献将HPV多重感染对宫颈癌前病变及宫颈癌的影响进行了综述。     

人乳头瘤病毒感染及其免疫学进展

人乳头瘤病毒(HPV)感染引起人皮肤和黏膜的多种良、恶性病变,如尖锐湿疣、宫颈上皮内瘤样变及宫颈癌等。HPV感染后可刺激宿主免疫系统(特异性免疫和非特异性免疫)产生一定的免疫应答;HPV亦通过多种免疫逃逸机制逃避宿主免疫系统的监视与清除。HPV与宿主免疫系统之间的相互作用决定了HPV感染后不同的临床表现(临床无症状或病变持续存在甚至发生癌变)。该文综述了HPV感染后宿主免疫反应及HPV免疫逃逸机制的研究进展。     

HPV16型E7抗原表位的研究进展

人乳头瘤病毒(HPV)常见型别中,良性型HPV6、11型和恶性型HPV16、18型等感染可以导致尖锐湿疣、宫颈上皮内瘤和宫颈癌等疾病^[1,2]。HPV16基因组中E7基因主要与细胞转化功能及致癌有关,由于HPV感染局部抗原呈递障碍^[3,4]、HPV抗原对局部免疫反应的负性调节^[5,6]和细胞毒性T淋巴细胞(cyto-toxic Tlymphocyte,CTL)难与HPV感染的角质形成细胞相互作用^[7]等原因,从感染早期到肿瘤形成期均可持续检测到E7蛋白的表达。该蛋白作为一种理想的免疫治疗靶抗原在研究中倍受重视。筛选和鉴定E7抗原CTL表位并进行特异性免疫治疗具有重要的临床应用价值。     

TCT联合高危型HPV检测在宫颈癌筛查中的应用

目的探讨TCT与高危型HPV单独及联合检测在宫颈癌筛查中的应用。方法选取2018年1月至2018年12月北京市大兴区人民医院接受阴道镜活检的491例患者作为研究对象。行TCT和高危型HPV检测,以病理学诊断为金标准,行方法学评价。结果宫颈活检组织病理CINⅠ级及炎症患者385例,TCT检查显示35.6%(137/385)为NILM,64.4%(248/385)为ASCUS及LSIL、ASC-H、HSIL;CINⅡ级和Ⅲ级宫颈癌患者共106例,TCT检查显示16.0%(17/106)为NILM,84.0%(89/106)为ASCUS及LSIL、ASC-H、HSIL。不同级别宫颈病变的TCT结果阳性率比较,差异具有统计学意义(χ~2=34.155,P0.05)。宫颈高级别病变中TCT阳性率明显高于低级别病变的阳性率,随着宫颈活检病理级别的升高,高危型HPV检测的阳性率升高,差异具有统计学意义(χ~2=10.710,P0.05)。高危型HPV检测的灵敏度93.36%(211/226)明显高于单独的TCT 77.43%(175/226)及两者联合检测70.80%(160/226),差异具有统计学意义(χ~2=38.777,P0.05)。两者联合检测的准确率及特异度高于两者单独检测,差异具有统计学意义(P0.05)。结论 TCT联合高危型HPV检测能够提高检测的准确性和特异性,是筛查宫颈癌的有效方式。     

CD1a和CD83分子在宫颈病变中的表达

目的 探讨不同宫颈病变中CD1a和CD83分子的表达。方法 免疫组化法分别检测30例宫颈癌患者、30例宫颈尖锐湿疣患者和30例慢性宫颈炎上皮组织中CD1a和CD83分子的表达。结果 当宫颈病变向宫颈癌进展,瘤细胞侵袭性增加时,未成熟的CD1a+树突细胞密度随之降低（慢性宫颈炎3.45个细胞/HPF, 尖锐湿疣2.89个细胞/HPF,宫颈癌2.41个细胞/HPF）。相比而言,尖锐湿疣皮损与慢性宫颈炎相比,成熟的CD83+树突状细胞密度有显著提高（尖锐湿疣0.057个细胞/HPF,慢性宫颈炎0.012个细胞/HPF）。但在宫颈癌中成熟的CD83+树突状细胞密度也有一定的提高（宫颈癌0.034个细胞/HPF）。宫颈癌组织中,HPV16/18型阳性率为56.67%,HPV6/11型阳性率为3.30%;宫颈尖锐湿疣组织中,HPV6/11型阳性率为73.30%,HPV16/18型阳性率为6.67%;慢性宫颈炎组织中,HPV6/11型阳性率为3.30%,HPV16/18型阳性率为0。结论　宫颈癌组织中抗原提呈细胞尚不足以引起免疫反应防止病变的侵袭发展。     

不同年龄患者HPV感染与宫颈病变风险的关系及对术后病变复发的预测

目的 探讨不同年龄患者人乳头瘤病毒(HPV)感染与宫颈病变风险的关系及对术后病变复发的预测价值。方法 选取2019年1月至2022年1月于联勤保障部队第901医院妇科门诊进行宫颈病变筛查并确诊宫颈病变的108例患者作为研究对象。所有患者按年龄分组,A组(18～35岁)42例,B组(36～55岁)36例,C组(>55岁)30例。所有患者术前均进行HPV检查,计算HPV载量,术后随访1年,于末次随访检测HPV,根据随访结果将所有患者分为术后复发组和术后未复发组。对比分析不同组别各级宫颈病变的HPV载量,采用Pearson相关性分析不同年龄患者HPV感染与宫颈病变风险的关系,采用Logistic回归分析术后病变复发的影响因素。结果 不同年龄组的各级宫颈病变HPV载量比较存在统计学差异(P<0.05),且A组各级宫颈病变HPV载量均高于B组,B组均高于C组(P<0.05),其中慢性宫颈炎HPV载量低于宫颈上皮内瘤变(CIN)Ⅰ,CINⅠ低于CINⅡ～Ⅲ,CINⅡ～Ⅲ低于宫颈癌,不同年龄患者HPV感染与宫颈病变风险均存在负相关关系(P<0.05);绝经、切缘状态、术后HP...     

性病门诊192例就诊者宫颈拭子HPV检测结果分析

目的:探讨女性宫颈HPV DNA检测在宫颈癌防治方面的意义.方法:采用聚合酶链反应(PCR),对192名女性宫颈进行HPV分型检测.结果:192例女性宫颈拭子HPV阳性96例,阳性率50%;高危型HPV(16/18)54例,阳性率28.1%;低危型HPV(6/11)42例,阳性率21.9%.结论:HPVDNA检测有利于宫颈癌的防治,是宫颈癌普查值得推荐的初筛试验.     

探讨女性生殖道高危型人乳头瘤病毒感染及其与宫颈癌病变的关系

目的:探讨女性生殖道高危型人乳头瘤病毒感染及其与宫颈癌病变的关系。方法:对宁波市北仑区第二人民医院2015年4月至2017年4月收治的120名行HPV感染及宫颈癌筛查的未孕女性的临床资料进行统计分析。结果:120名女性中,HPV阳性20名,HPV阳性率为16. 7%,其中50岁～59岁女性HPV阳性率最高,为25. 0%;其次为20岁～29岁(18. 1%)、45岁～49岁(16. 7%);最后为35岁～39岁(16. 7%)、30岁～34岁(16. 0%)、40岁～44岁(13. 0%)。但不同年龄女性HPV阳性率之间的差异均无统计学意义(all P> 0. 05); CIN9例,现患率为7. 5%,其中CINⅠ6例,CINⅡ/Ⅲ3例,现患率分别为5. 3%、2. 2%;宫颈癌1例,现患率为0. 8%。不同年龄女性CIN、宫颈癌现患率之间的差异均无统计学意义(all P>0. 05); N-CIN、CINⅠ、CINⅡ、CINⅢ、宫颈癌女性的HPV阳性率10. 9%、66. 7%、50. 0%、100. 0%、100. 0%逐渐提升,差异具有统计学意义(P <0. 05)。结论:女性生殖道高危型人乳头瘤病毒感染与宫颈癌病变呈显著的正相关关系。     

HPV感染高危女性宫颈癌认知程度影响因素及预防性HPV疫苗接种效果调查分析

目的探究人乳头瘤病毒(HPV)感染高危女性对宫颈癌病变情况的认知程度及HPV疫苗接种的预防效果。方法选取于我院门诊行宫颈癌筛查的1244例妇女为观察对象,采用2代杂交捕获法检测出HPV感染高危者共445例,未检测出HPV感染高危者及无性生活史女性共799例,以自愿接种HPV疫苗者为研究组,拒绝接种HPV疫苗者为对照组,调查随访50个月,比较HPV持续性感染、HPV16/18型机会感染、用药不良反应以及宫颈上皮内瘤样病变(CIN)Ⅰ～Ⅱ级发生情况。结果宫颈癌筛查的意义以及宫颈癌能否痊愈2项知晓率较高,分别为53.50%、65.00%,其余宫颈癌相关知识的知晓率相对较低;认知良好者在居住地、年龄、婚姻情况、职业、家庭收入等方面优于认知不良者(P0.05);多因素Logistic回归分析得出,居住地、婚姻情况、年龄、家庭收入以及受教育年限是宫颈癌认知程度的主要影响因素。研究组持续性HPV感染、HPV16/18型机会感染以及宫颈CINⅠ~Ⅱ级发生率明显低于对照组(P0.05)。结论 HPV感染高危女性对宫颈癌的认知度低,影响因素复杂,HPV疫苗、提高宫颈癌检查、加强宣传对HPV感染有保护作用,但接种HPV疫苗体系仍需完善。     

人乳头瘤病毒16/18分型在宫颈癌初筛阳性分流中的应用价值

目的:探讨人乳头瘤病毒(human papilloma virus,HPV) 16/18分型在宫颈癌初筛阳性分流中的价值。方法:选择在南京医科大学附属无锡妇幼保健院进行宫颈癌筛查的2000例女性作为研究对象,均行薄层液基细胞学检查和二代杂交捕获法高危型HPV DNA检测,任一项阳性召回行阴道镜检查和HPV 16/18分型检测,阴道镜检查异常者行多点活检。随机选择10. 00%初筛结果阴性患者行阴道镜检查,异常者行多点活检。结果:初筛总阳性361例(18. 05%),其中单独高危型HPV DNA检测阳性168例(8. 40%),单独液基细胞学阳性47例(2. 35%),二者均为阳性146例(7. 30%)。HPV 16/18检测阳性276例(76. 45%)。初筛阳性女性通过HPV 16/18检测分流的灵敏度、特异度、宫颈高度病变预测值和阴性预测值分别为87. 18%、53. 47%、24. 64%和95. 98%。仅行高危型HPV DNA检测或者液基细胞学检查时阴道镜转诊率可达18. 05%;初筛阳性后进行HPV 16/18检查时阴道镜转诊率为13. 80%,差异具有统计学意义(P <0. 05)。结论:通过对宫颈癌初筛阳性患者开展HPV 16/18分型检测能够提高宫颈癌及癌前病变检出率,降低阴道镜转诊率。     

Differences in immunological alterations and underlying viral infections in two well-defined severe drug eruptions

Background. Similar drugs (e.g. anticonvulsants) have been implicated in the development of two distinct forms of severe cutaneous drug reactions, Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug–induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS). Aim. To investigate immunological alterations and underlying viral infections that could contribute to the variability in the clinical presentations of these diseases. Methods. We retrospectively analysed clinical variables, serum immunoglobulin levels, numbers of circulating white blood cells, lymphocytes and their subsets, serum levels of several cytokines, and underlying viral infections in both drug reactions, using samples obtained at onset from 9 patients with SJS/TEN and 19 patients with DIHS/DRESS. Results. There were significant differences between the two drug eruptions in the duration of drug intake before onset, the levels of IgG, IgA and IgM, the numbers of circulating white blood cell, lymphocyte, CD3+ T cell and CD8+ T cells, the serum levels of interferon-γ, and the titres of anti-herpes simplex virus IgG at onset. Conclusions. The difference in the pattern of immune responses shaped in part by previous and underlying viral infections at the time of drug exposure could cause a marked deviation in the pathological phenotype of severe drug eruptions. Elucidating these host factors may provide a basis for therapeutic approaches in patients with severe drug reactions.     

皮肤组织常驻记忆T细胞在白癜风炎症反应中的作用

【摘要】 组织常驻记忆T细胞由初始T细胞受到刺激后形成，并驻留在外周组织，介导机体对类似刺激迅速产生免疫反应。虽然这种免疫反应有助于保护机体对抗局部感染，但在自身免疫相关性皮肤病如白癜风中组织常驻记忆T细胞在皮肤的长时间驻留会导致疾病反复发作。本文对组织常驻记忆T细胞与白癜风之间的关系及潜在治疗靶点进行综述。     

Leishmaniasis,contact hypersensitivity and graft‐versus‐host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance

Please cite this paper as: Leishmaniasis, contact hypersensitivity and graft‐versus‐host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance. Experimental Dermatology 2010; 19 : 760–771. Abstract: Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node–resident DC. The skin is the primary interface between the body and the environment and host’s various DC subsets, including dermal DC (dDC) and Langerhans cells (LC). Because of their anatomical position in the epidermis, LC are believed to be responsible for induction of adaptive cutaneous immune responses. The functions of LC and dDC in the skin immune system in vivo are manifold, and it is still discussed controversially whether the differentiation of T‐cell subtypes (e.g. effector T cells and regulatory T cells) may be initiated by distinct DC subtypes. As skin DC are able to promote or downmodulate immune responses, we chose different skin diseases (cutaneous leishmaniasis, contact hypersensitivity, UV radiation‐induced suppression, and graft‐versus‐host disease) to describe the biological interactions between different DC subtypes and T cells that lead to the development of efficient or unwanted immune responses. A detailed knowledge about the immune modulatory capacity of different cutaneous DC subsets might be helpful to specifically target these cells through the skin during therapeutic interventions.     

Dendritic cell activation by danger and antigen-specific T-cell signalling

Recent transplantation, animal and in vitro studies suggest a dependence of some immune reactions on tissue damage. Although many factors involved in enhancing immune responses through tissue damage have yet to be identified, recent data suggests that one of the targets of these cellular stress factors is the bone marrow derived dendritic cell (DC). DC are potent initiators of primary immune responses and hold the key to immune reactions through their ability to sense changes in their local environment and respond appropriately to induce T-cell immunity, or possibly tolerance. In the lymph node, DC are also influenced by antigen-specific signalling from T cells, which may extend and amplify DC antigen presenting capabilities, especially for the stimulation of cytotoxic responses. It now appears that both tissue damage and antigen-specific T-cell derived signals act together on the DC to promote the appropriate immune reaction to antigen. Thus DC antigen presenting behaviour is not only dependent on the context of antigen encounter in the periphery, but also on the availability of antigen-specific T cells and their T-cell receptor specificities.     

光动力疗法诱导抗肿瘤免疫的研究进展

光动力疗法不仅直接杀死局部肿瘤细胞,还可以激活局部与系统性抗肿瘤的免疫反应,其机制涉及通过热休克蛋白等促进肿瘤抗原释放和增强免疫细胞在炎症反应中的作用.免疫佐剂和其他免疫疗法与光动力疗法联合使用,可提高光动力疗法治疗肿瘤的疗效.利用上述免疫机制建立肿瘤疫苗,能够抑制肿瘤原发灶和转移灶的生长,有望成为光动力疗法抗肿瘤免疫领域的新热点.     

Melanoma vaccines: early progress and future promises

Melanoma vaccines aim to stimulate host immune responses against the patient's own tumor. A large number of immunotherapeutic interventions have been already studied in small-scale phase I-II trials. These approaches have been based upon presumptions of investigators, including the format in which antigen would be best administered (peptide, protein, tumor lysate, whole tumor cells or genetic material coding for the proteins of interest), the antigen delivery system and adjuvants (cytokines and dendritic cells, gene-therapy), and the route/schedule of administration. Several approaches have already demonstrated an impact on the immune system but very rarely to date upon the patients' clinical disease outcome. Recent developments in cancer immunology have helped elucidate the role of the main players in the development of host anti-tumor immune responses (including the tumor cells, different T cell subsets, and dendritic cells). These research efforts have provided the basis for the multiple vaccine trial interventions that have been proposed to boost host anti-tumor immune responses. They also have allowed the development of multiple new tools to monitor immune responses in vaccinated patients (including ELISPOT, tetramers and intracellular cytokine-release assays, as well as real-time-PCR and analysis of the T cell receptor). Although multiple cancer vaccine approaches have successfully stimulated T cell immune responses in patients with cancer, the most promising ones need to be formally tested for their ability to improve both the immunological and clinical status of the vaccinated patients in phase III randomized clinical trials.     

光动力疗法诱导抗肿瘤免疫的研究进展

光动力疗法不仅直接杀死局部肿瘤细胞,还可以激活局部与系统性抗肿瘤的免疫反应,其机制涉及通过热休克蛋白等促进肿瘤抗原释放和增强免疫细胞在炎症反应中的作用.免疫佐剂和其他免疫疗法与光动力疗法联合使用,可提高光动力疗法治疗肿瘤的疗效.利用上述免疫机制建立肿瘤疫苗,能够抑制肿瘤原发灶和转移灶的生长,有望成为光动力疗法抗肿瘤免疫领域的新热点.     

Mechanisms of resolution of allergic contact dermatitis

Photoallergic and allergic contact dermatitis are examples of type IV hypersensitivity reactions that involve T cell-mediated immune responses against haptens that come into contact with the skin. These two types of allergies differ in that for routine contact allergens, the hapten is usually a chemically reactive species that readily couples to host proteins; for photoallergic reactions, UV light (320–400 nm) is necessary to generate (“photoactivate”) the chemically reactive hapten. From this point on, both photoallergic and allergic contact dermatitis are likely to proceed along the same pathways. For both types of cutaneous delayed-type hypersensitivity, there are naturally occurring mechanisms that terminate this type of T cell-mediated inflammation (tolerance induction). An important tolerance mechanism in the skin involves the induction of T-cell clonal anergy by “amateur” antigen-presenting cells such as keratinocytes. Advances in the understanding of the molecular pathways of T-cell activation and inactivation by antigen-presenting cells have identified critical signaling molecules such as B7/BB-1 antigen. The overexpression of these signaling molecules by the keratinocytes of transgenic mice disrupts the normal kinetics of resolution of murine contact hypersensitivity. These animals have prolonged contact hypersensitivity reactions that resemble some chronic dermatologic conditions in humans. This animal model may be a useful tool to better understand chronic allergic and photoallergic contact dermatitis.     

白念珠菌、烟曲霉及新生隐球菌感染的宿主特异性免疫应答研究进展

白念珠菌、烟曲霉及新生隐球菌是3种机会致病真菌。这些真菌一旦感染人体,即与机体免疫系统相互作用,激活机体的天然免疫,继而产生特异性细胞免疫及体液免疫应答,其中特异性细胞和体液免疫应答对宿主抵御感染和防止菌体免疫逃逸发挥重要作用。概述近几年有关白念珠菌、烟曲霉及新生隐球菌感染的特异性免疫应答的研究现状,并分析3种真菌免疫的异同点,以期为开展此类研究提供有益借鉴。     

银屑病与特应性皮炎的T细胞免疫失衡机制研究进展

 银屑病和特应性皮炎是常见的以T细胞介导免疫炎症和角质形成细胞异常分化为特征的炎症性疾病。两种疾病在免疫发病机制、临床特征、组织病理、共患病和治疗方法方面有很多共性,但也存在差异。两种疾病的相似性为表皮角质形成细胞对T细胞产生的细胞因子发生异常反应,其增殖和分化发生改变,这也是两种疾病表型的主要原因。但两种疾病的T细胞极化方向存在差异。本文重点从T细胞免疫失衡机制方面对银屑病与AD两种疾病的共性与差异进行综述。