皮肤共生菌调节机体免疫应答的研究进展北大核心CSCD

皮肤是人体最大的器官,也是机体防御外部环境有害物质入侵的第一道防线。皮肤除了由角质形成细胞形成的物理屏障外,还能分泌抗菌肽、活性氧和游离脂肪酸等,对入侵皮肤表皮的病原微生物起直接杀伤作用,是人体先天免疫的重要组成部分。在皮肤表面生存着大量的微生物,包括细菌、真菌、病毒、衣原体和某些原虫,这些微生物对人体的免疫应答至关重要,     

孢子丝菌感染与机体免疫研究进展

孢子丝菌病是常见的深部真菌感染,孢子丝菌侵入机体后,通过自身毒力因子与免疫系统对抗,从而使感染迁延不愈。孢子丝菌感染与机体免疫作用机制的研究相对有限,同时也是目前本领域研究热点之一。本文将从孢子丝菌感染途径、机体的抗孢子丝菌免疫以及孢子丝菌的免疫逃逸机制等几方面,对相关研究进展进行综述。     

皮肤真菌感染中的免疫应答

由于各种众所周知的原因,导致免疫功能低下的患者不断增多,真菌感染率逐年攀升,而大多数关于真菌病的免疫学研究多局限于深部真菌感染。针对不同的皮肤真菌感染,对侵犯皮肤的真菌抗原性和机体对病原体的免疫应答加以介绍,并解释了脂溢性皮炎和特应性皮炎与真菌感染的关系。     

紫外线照射下microRNA在皮肤中的应答机制研究进展

紫外线(UV)是环境中普遍存在的致癌物,可分为:短波UVC(200～280 nm),中波UVB(280～320 nm)和长波UVA(320～400nm).皮肤常会暴露在UV中,尤其是UVA和UVB.其对皮肤的不良影响备受关注,如:红斑、老化、免疫抑制和癌症.为了对抗这些不良影响并维持染色体组的完整性,细胞发动一系列保护...     

免疫检查点抑制剂所致皮肤免疫相关不良反应的研究进展

【摘要】 作为一类新型的抗癌药物,免疫检查点抑制剂在被广泛应用于多种肿瘤治疗的同时,也导致许多免疫相关不良反应,其中以皮肤相关不良反应最为常见。皮肤免疫相关不良反应发病早、大多数程度较轻,但也会出现危及生命的情况。本文综述免疫检查点抑制剂所致皮肤免疫相关不良反应的研究进展。     

免疫检查点在皮肤肿瘤中的研究进展

近年来研究发现,免疫检查点(CTLA-4、PD-1、TIM-3、TIGIT和LAG-3等)表达于免疫细胞表面,与肿瘤的增殖、侵袭和转移紧密相关。免疫检查点抑制剂,已广泛地应用于皮肤肿瘤的临床治疗,并取得了显著的疗效。本文将从免疫检查点的类型、作用机制、其在皮肤肿瘤中的研究及临床应用等方面进行系统综述。     

皮肤T细胞淋巴瘤免疫微环境研究进展

【摘要】 皮肤T细胞淋巴瘤（CTCL）是一组具有不同临床表现、病理学改变、免疫表型和分子生物学特征的异质性肿瘤,其发病机制不完全清楚。越来越多的证据表明,肿瘤免疫微环境的组成和功能对于CTCL的发生发展起着重要作用,深入了解其微环境的组成有助于寻找更有效的抗肿瘤免疫治疗方法,同时帮助临床医生更加准确地判断疾病预后。本文就近年来关于CTCL免疫微环境的基础和临床研究进展作一综述。     

角质形成细胞与皮肤免疫研究进展

角质形成细胞(keratinocytes,KCs)是表皮的重要组成部分,近年的研究发现其在皮肤免疫反应中发挥着多种作用,包括免疫监视、免疫介质的释放、抗原提呈、介导炎症反应等。明确角质形成细胞的生理功能及在皮肤免疫中的作用机制,可为疾病的治疗及研究提供新的思路。     

Th22细胞与皮肤免疫的研究进展

Th22细胞是一种最新发现的辅助性T细胞亚群,其表型为CCR6＋CCR4＋CCR10＋,关键转录因子是芳香烃受体（aryl hydrocarbon receptor,AHR）,主要分泌的细胞因子为IL-22。Th22细胞主要参与皮肤的自稳调节和病理状态。在正常情况下,与其他的细胞亚群互相调控,使机体处于平衡状态。综述近年Th22细胞在皮肤免疫以及皮肤病中作用的研究进展。     

BALB/c小鼠对马尔尼菲篮状菌黑素的免疫应答

目的:明确马尔尼菲篮状菌酵母细胞黑素能否刺激BALB/c小鼠产生免疫应答。方法:利用马尔尼菲篮状菌酵母细胞黑素颗粒作为抗原免疫BALB/c小鼠,制备马尔尼菲篮状菌黑素抗体,采用凝集试验和ELISA间接法进行检测。结果:免疫接种后的小鼠出现不同程度腹水、脱毛或脾脏肿大等;免疫小鼠的腹水、血清和杂交瘤细胞培养上清与马尔尼菲篮状菌黑素颗粒均产生凝集反应,ELISA法检测抗体OD值依次为1.635±0.085、1.820±0.249、0.671±0.142。结论:马尔尼菲篮状菌黑素可以刺激BALB/c小鼠产生抗体。     

Ubiquitination in host immune response to human papillomavirus infection

Human papillomavirus (HPV) infection with low-risk or high-risk subtypes is very common. Infection with HPVs is often a major causative factor for the development of cutaneous benign lesions, cervical cancer, and a number of other tumors. The mechanisms of host immunity to prevent and control HPV infection still remain unclear. The importance of ubiquitination (or ubiquitylation) as an intracellular proteasomal-mediated protein degradation pathway, and as an important modulator for the regulation of many fundamental cellular processes has been valued over the last decade. Although the molecular and cellular mechanisms are not completely established, the critical role of ubiquitination in host immune response to HPV infection has become increasingly apparent. This review summarizes current knowledge on the possible role that ubiquitination plays in regulating the host immune response during HPV infection. Targeting the components of the ubiquitin system might offer potential therapeutic strategies for HPV-related diseases in the future.     

Basal cell carcinoma progression correlates with host immune response and stromal alterations: a histologic analysis

Neoplastic progression is characterized in part by escape from immune surveillance and formation of growth-permissive stroma. Basal cell carcinoma (BCC) can be subclassified into low- and high-risk types for local recurrence. To determine whether these types of BCC correlate with alterations in local host immune response and stroma and whether these changes follow stepwise histologic progression from low- to high-risk subtypes, we assessed the clinicopathologic features in 175 consecutive primary (nonrecurrent) BCC excision specimens. BCCs exhibited a significantly higher frequency of mixed rather than homogeneous growth patterns (76% vs. 24%, P=0.0001). Nodular (84%) was the most common pattern identified followed by superficial (77%), infiltrative (27%), morpheic (5%) and micronodular patterns (4%). Only superficial (12% of all BCC) and nodular (12%) patterns were identified in BCC with a homogeneous histologic phenotype. Micronodular and infiltrative-morpheic patterns were not identified together in mixed patterned BCCs, and these high-risk types were contiguous with nodular BCC. Superficial predominant BCC (major growth pattern) was significantly associated with trunk and extremity location (76%) and skin without solar elastosis (82%), whereas BCC harboring a nodular growth pattern component was significantly associated with a head and neck location (63%) and the presence of adjacent solar elastosis (all P< or =0.03). Significant correlations were identified for BCC subtypes with inflammatory and stromal alterations: superficial BCC with old regression and moderate to dense peritumoral lymphocytic infiltrates; high-risk types correlated with active regression; infiltrative and morpheic BCC with fibrosing tumor stroma; and micronodular BCC with loss of both host inflammatory and stromal tumor responses. Evaluating the theoretical histologic stepwise model of BCC progression (superficial-to-nodular-to-micronodular, or superficial-to-nodular-to-infiltrative-to-morpheic BCC types) revealed significant linear correlations with host response and alterations of tumor stroma (r=0.54, P=0.0001). BCC exhibit distinct epithelial-stromal-inflammatory patterns that correlate with BCC subtype and tumor progression. This ostensible pathway of diminishing host response and gain of permissive tissue environment highlights neoplastic evolution from low to high risk for local recurrence of BCC and implicates a histologic continuum reflecting dynamic host-BCC interactions.     

Lack of host cellular immune response in eruptive molluscum contagiosum

A lack of cellular immunity on the part of the host has been incriminated as the cause of the persistence of the cutaneous lesions of molluscum contagiosum. We present a patient in the eruptive phase of the disease, confirming the absence of T-lymphocyte and natural killer cell subsets in the base of these typical lesions, using a panel of monoclonal antibodies. We also report the observation of lipid material ultrastructurally (confirmed by osmium staining on fresh-frozen tissue), as well as cross-reactivity immunocytochemically of the antigens on these molluscum bodies with antigens normally present on macrophages, as defined by DAKO-macrophage monoclonal antibodies. We have considered the possible role of these findings in the lack of host cellular responsiveness in the eruptive phase of the disease.     

Systemic PPARgamma ligation inhibits allergic immune response in the skin

We have shown previously that specific ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit the systemic allergic immune response. The objective of this study was to investigate the impact of PPARgamma-ligand treatment on the local allergic immune response. We established a murine model exhibiting clinical and histological features of AD-like skin lesions with high reproducibility. In this model, the PPARgamma ligand was applied in an either preventive or therapeutic manner via systemic and local routes. The affected skin areas were assessed by standardized skin score, histological analyses, and immunohistochemical examinations. Our data show that systemic application of PPARgamma ligand by a preventive protocol led to significantly reduced onset of eczematous skin lesions. This was confirmed by histology, showing decreased skin thickness accompanied by significantly reduced infiltrations of CD4+ and CD8+ lymphocytes but also mast cells. Additionally, early allergen-specific IgE and IgG1 responses were reduced (day 21/35), whereas IgG2a levels remained unchanged. In conclusion, our results demonstrate that PPARgamma-ligand treatment inhibits not only systemic allergic immune response, but also local allergen-mediated dermatitis. Our findings point to therapeutic strategies, including a PPARgamma-ligand-based treatment.     

The skin immune system: lupus erythematosus as a paradigm

Lupus erythematosus (LE) was first described as a clinical dermatological entity in 1851. The possibility of serious systemic manifestations became recognized by 1872 as the result of the work of M. Kaposi. Since then, it took a long time before LE was recognized to be an immunological disease. Recognition of antinuclear antibodies and their deposition at the basal membrane region in skin resulted in two concepts of LE pathogenesis. In one, antibody complexing and complement activation with generation of the membrane attack complex (C5–C9) is thought to be the origin of the chronic inflammatory reaction. In the other, antibody deposition enables antibody dependent cellular cytotoxity, leading to hydropic degeneration of the basal epidermal layer and subsequent chronic inflammation. Norris postulated in 1993, that the epidermis acts as a pro-inflammatory organ, in which an UVB-induced increase in cytokine production is followed by increased expression of adhesion molecules on keratinocytes as well as dermal endothelial cells. Translocation of certain antigens (i.e. Ro & La) to which circulating auto-antibodies exist in LE, enables recognition by adhesion molecule directed skin-invading T cells with subsequent cytotoxic effector activity. A persistent chronic inflammatory reaction then ensues. A similar development in knowledge may be seen in the history of immunodermatology. Originally, lupus erythematosus could not be recognized as an immune disease, since concepts of immunology were virtually non-existent when LE was first described. Immunology, in the first half of this century, was mainly antibody-oriented and thus came the concept of (S)LE as an antibody-mediated disease. Subsequently, the role of cellular immunological pathways came into focus, and cellular effector mechanisms were introduced in LE pathogenesis concepts. Ultimately, the recognition of subsystems within the (skin) immune system with cytokine networks, dermal microvascular units, and a complex interplay of both cellular and humoral immune mechanisms has resulted in a more complex but also more appreciable postulate of the pathogenesis of lupus erythematosus. The understanding of a complex immunodermatological disease is facilitated by taking into account the possible complicated interplay of subsystems within the skin immune system (SIS), with both humoral and cellular effector mechanisms.     

Fractional ablative laser skin resurfacing: a review

Ablative laser technology has been in use for many years now. The large side effect profile however has limited its use. Fractional ablative technology is a newer development which combines a lesser side effect profile along with similar efficacy. In this paper we review fractional ablative laser skin resurfacing.     

Coccidioidomycosis and the skin: a comprehensive review

Coccidioidomycosis is a highly prevalent disease in the Western hemisphere. It isconsidered one of the most virulent primary fungal infections. Coccidioides specieslive in arid and semi-arid regions, causing mainly pulmonary infection throughinhalation of arthroconidia although many other organs can be affected. Primaryinoculation is rare. Since the first case of coccidioidomycosis was reported in 1892,the skin has been identified as an important target of this disease. Knowledge ofcutaneous clinical forms of this infection is important and very useful forestablishing prompt diagnosis and treatment. The purpose of this article is toprovide a review of this infection, emphasizing its cutaneous manifestations,diagnostic methods and current treatment.