变应原特异性免疫治疗机制

从变应原特异性免疫治疗的极早期脱敏效应、对调节性T细胞的影响、对抗体类型的影响、对效应细胞趋化和功能的影响等方面对该疗法的作用机制进行综述。其中,变应原特异性效应T细胞向Treg细胞的转化是诱导变应原特异性免疫耐受的关键。     

舌下免疫治疗的免疫学机制

舌下免疫治疗(sublingual immunotherapy,SLIT)通过舌下途径给予变应原诱导变态反应性疾病患者产生变应原特异性免疫耐受,其疗效和安全性已得到广泛认同。然而,目前对SLIT确切机制的认识仍然有限。一般认为SLIT与皮下免疫治疗(subcutaneous immunotherapy,SCIT)相似,可降低患者体内特异性IgE水平并诱导产生保护性IgG4;同时能抑制患者皮肤黏膜局部炎症效应细胞的募集及活性。SLIT的另一个重要作用是将患者体内Th2型为主的免疫反应转变为Th1型反应。目前越来越多的证据显示调节性T淋巴细胞(regulatory T cell,Treg)参与变态反应性疾病的控制,虽然尚缺乏确切证据,但Treg可能在SLIT中起重要作用。更多Treg与变应原外周免疫耐受之间关系的研究,将有助于SLIT机制的进一步阐明。     

调节性T细胞在特异性免疫治疗中的作用

调节性T细胞是一类具有免疫抑制作用的T细胞亚群,在变态反应性疾病的特异性免疫治疗中具有重要作用,其可能通过细胞与细胞之间直接作用及通过上调IL-10及转化生长因子β起免疫作用。     

变应原特异性免疫治疗的研究进展

变应原特异性免疫治疗(Allergen-specific immunotherapy, ASIT)是现阶段唯一针对病因治疗且能长时间持续减轻过敏症状,改变自然病程的治疗方法。目前已在过敏性疾病的临床治疗中广泛应用,并取得良好的治疗效果。随着治疗药物和治疗途径的不断改良,ASIT在过敏性疾病的治疗中显示出不可比拟的优势。本文对ASIT作用机制、应用药物、给药途径和禁忌症方面进行综述,旨在为ASIT的临床治疗提供参考。     

屋尘螨变应原免疫治疗炎症细胞因子与特异性IgE和IgG4的动态相关分析

目的 分析屋尘螨(dermatophagoides pteronyssinus,Der p)的sIgE和sIgG4与炎症细胞因子治疗前后的动态相关性,探讨标准化Der p变应原免疫治疗(allergen immunotherapy,AIT)过程的可能机制.方法 选取55例在广州医科大学附属第一医院和珠海市人民医院接受AIT的鼻炎或鼻炎合并哮喘患者,分别在治疗前、治疗后4个月与12个月检测血清IL-5、IL-8、IL-10、IL-13、IL-17和肿瘤坏死因子α共6种炎症细胞因子的水平.结果 AIT后,Der p sIgE水平曾一度升高,但随之开始下降,随着治疗的进行,Der p sIgG4水平均显著性升高.虽然对55例患者细胞因子AIT前后相比无明显差异,但是进行年龄分组(儿童/成人)和疾病分组(鼻炎/鼻炎合并哮喘)后,AIT后细胞因子水平有组间差异,如IL-5水平儿童组高于成人组,且儿童组治疗12个月比治疗前降低;AIT 12个月,鼻炎合并哮喘组IL-5水平较治疗前低(P＜0.05).Der p sIgE和sIgG4与细胞因子在不同免疫治疗阶段与不同的细胞因子有相关性,特别是sIgG4的升高在不同的免疫治疗阶段与不同的细胞因子的变化有关.结论 AIT后sIgG4升高,sIgE降低.且儿童与成人组,鼻炎与鼻炎合并哮喘组的细胞因子变化水平不同,Der p sIgE和sIgG4水平与细胞因子在AIT过程存在一定的相关性,说明sIgE和sIgG4在AIT中反映了机体的免疫状态.     

支气管哮喘的特异性免疫治疗作用机制研究进展

<正>支气管哮喘(简称哮喘)是由气道内的炎症细胞、结构细胞和细胞组分共同参与的慢性炎症性疾病,与遗传和过敏症相关,属于I型超敏反应。哮喘的治疗方法众多,但目前尚无能够完全治愈的药物,特异性免疫治疗(SIT),即脱敏疗法[1],是世界卫生组织推荐的唯一针对哮喘病因的治疗方法。临床疗效观察证实,SIT较其他治疗能更有效地改善患者的敏感状态及临床症状、减少血清总IgE水平及平喘药物使用剂量[2,3]。随着SIT的临床疗效被越来     

变应性疾病特异性免疫治疗机制研究进展

特异性免疫治疗是特异性Ⅰ型变态反应性疾病的惟一有效的可以改变其自然病程的方法.虽然其机制不十分清楚,但已有很大进展.随着变应原疫苗的标准化及治疗方案的改进,使其疗效和安全性不断提高.本文综述了近几年来对特异性免疫治疗机制方面的研究进展.     

肝细胞癌的免疫治疗（下）

5．肿瘤逃逸机制 肿瘤从免疫系统产生了很多逃逸机制来抑制抗肿瘤反应。产生免疫抑制因子、增加调节性T细胞、下调肿瘤抗原和MHC分子都是肿瘤细胞用以逃避免疫识别的机制。已有很清楚的证据显示发生HCC能导致肿瘤特异性免疫反应受到抑制。尤其是我们已经证实尽管在超过50％的HCC患中检测到肿瘤特异性的细胞和体液免疫反应，但是HCC仍然有所进展。虽然有抗原特异性T细胞的出现但HCC肿瘤仍然进展，这增加了对免疫治疗该肿瘤的有效性的关注。因为下面会展示，HCC的发展导致一系列不同的免疫机制，结果就是HCC患中肿瘤特异性免疫反应的抑制。[第一段]     

变应原特异性免疫治疗在儿童过敏性疾病中的研究进展

IgE介导的儿童过敏性疾病种类较多,从儿童出生后早期的食物过敏及湿疹,到青少年期逐渐出现的变应性鼻炎和支气管哮喘等,儿童过敏性疾病的发病率在近几十年有不断增长趋势。针对儿童的IgE介导的过敏性疾病的治疗措施主要包括以下几个方面,避免过敏原,药物治疗以及变应原特异性免疫治疗(specific immunetherapy,SIT)。虽然避免过敏原及药物治疗可以暂时的缓解过敏性疾病的临床症状,但是只有SIT是针对病因的治疗,可以使过敏症状达到长时间的缓解,能够真正的改变儿童过敏性疾病的进程。     

屋尘螨脱敏治疗对变应性鼻炎及哮喘患者血清粉尘螨特异性IgG4抗体的影响

目的探讨屋尘螨特异性免疫治疗对血清屋尘螨和粉尘螨特异性IgG4水平的影响。方法32例接受安脱达屋尘螨特异性免疫治疗4-14个月的变应性鼻炎和支气管哮喘患者,抽取其治疗前后血清共64份。采用四层双抗夹心酶联免疫吸附法测定患者血清特异性IgG4抗体。结果脱敏治疗后的患者血清中屋尘螨和粉尘螨特异性IgG,抗体水平均有显著上升（P〈0．0001）,且IgG4抗体的增长水平与治疗时间呈正相关。结论使用屋尘螨脱敏疫苗治疗所产生的IgG4抗体能同时识别屋尘螨和粉尘螨两种抗原,从而使机体产生对这两种致敏原的免疫保护作用。     

Immunotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related death worldwide and efficient treatment options are urgently needed. Based on its pathogenesis, in addition to a number of correlative studies, immunotherapy represents a potential therapeutic option for patients with HCC. However, tumors have also evolved numerous immune escape mechanisms, including the generation of cells with immune suppressor functions, such as Tregs and myeloid-derived suppressor cells. It has been shown that these suppressor cells mask tumor-specific immune responses in patients with HCC. Different immunotherapeutic approaches including peptide- and dendritic cell-based therapies have demonstrated promising results in patients with HCC. However, we propose that any of these immunotherapeutic approaches needs to be combined with a therapy specifically targeting suppressor cells in HCC.     

Mechanisms of Sublingual Immunotherapy

Allergen-specific sublingual immunotherapy is now recognized to be an efficacious and well-tolerated treatment for allergic rhinitis. Emerging treatment strategies are also aimed at the primary treatment of allergic asthma, particularly allergy to house dust mites. Knowledge of the exact mechanisms of action of sublingual immunotherapy is at a basic level, although there appear to be similarities to the immunological changes seen in subcutaneous immunotherapy. An improved understanding should allow the development of more effective treatment programs and widen the potential use of this form of immunotherapy. This review discusses the possible mechanism of action of sublingual immunotherapy, including data from animal and clinical studies, while comparing this with the current understanding of subcutaneous immunotherapy.     

Recent advances in autoimmune pancreatitis: concept,diagnosis, and pathogenesis

Recent advances support the concept of autoimmune pancreatitis (AIP) as a unique systemic disease, because it shows occasional extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialoadenitis, and retroperitoneal fibrosis, pathological features similar to those of fibrosis, and abundant infiltration of IgG4-positive plasma cells, and it is steroid responsive. Based on these findings, several diagnostic criteria have been proposed. Although AIP is accepted worldwide as a unique clinical entity, its pathogenetic mechanism remains unclear. To clarify its pathogenesis, its genetic background, humoral immunity, candidate target antigens including self-antigens and molecular mimicry by microbes, and cellular immunity including regulatory T cells, the complement system, and experimental models are reviewed. On the basis of this review, we hypothesize that the pathogenesis of AIP involves a biphasic mechanism consisting of “induction” and “progression.” In the early stage, the initial response to self-antigens [lactoferrin, carbonic anhydrase (CA)-II, CA-IV, pancreatic secretory trypsin inhibitor, and α-fodrin] and molecular mimicry (Helicobacter pylori) are induced by decreased naïve regulatory T cells (Tregs), and T-helper (Th) 1 cells release proinflammatory cytokines [interferon-γ, interleukin (IL)-1β, IL-2, and tumor necrosis factor α]. In the chronic stage, progression is supported by increased memory Tregs and Th2 immune responses. The classical complement system pathway may be activated by the IgG1 immune complex. As Tregs seem to play an important role in progression as well as in induction of the disease, further studies are necessary to clarify the pathogenesis of AIP.     

Does Specific Immunotherapy Injection Cause an Increase in Bronchial Reactivity?

Background. Several well-controlled studies have proven the clinical benefit of specific immunotherapy (SIT) for seasonal allergic rhinitis (AR). However, whether subcutaneous SIT injection could cause a transient increase in bronchial reactivity (BR) remains unknown. Objective. To investigate whether subcutaneous SIT injection, either during or outside the pollen season, could cause an increase in BR in children with pollen allergy. Methods. Twenty-two children (mean age 13.6 ± 0.7 years) with AR who were receiving maintenance SIT for 15 months were included in the study. Pre-injection BR of the patients was evaluated with methacholine provocation test immediately before maintenance dose of SIT during the peak pollen season and outside the season. The post-injection test was administered 24 hours after SIT injection. Results. There was no difference in FEV₁ measures recorded during [98(93-109)%] and outside [102(96-111)%] the pollen season. There was no significant difference between pre- [64(7-64)mg/mL] and post-allergen injection [32(7.5-64) mg/mL] BR outside the pollen season (p = 0.9). A trend towards improvement following allergen injection [64(5.4-64)] as compared to pre-allergen injection [14.6(3.5-64)] was shown during the pollen season (p = 0.053). Although PC20 measures in the pollen season were lower than outside the season, the difference was not significant. The percentage of the patients with bronchial hyperreactivity was 62% during and 43% outside the season. Conclusion. SIT injections both during and outside the pollen season cause no increase in BR in children with AR. This calls into question the necessity of empirical dose reduction during the pollen season.     

Mechanisms of Allergen-Specific Immunotherapy and Novel Ways for Vaccine Development

Allergen-specific immunotherapy (SIT) is the only available curative treatment of allergic diseases. Recent evidence provided a plausible explanation to its multiple mechanisms inducing both rapid desensitization and long-term allergen-specific immune tolerance, and suppression of allergic inflammation in the affected tissues. During SIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T cells, which suppress proliferative and cytokine responses against the allergen of interest. Regulatory T cells are characterized by IL-10 and TGF-beta secretion and expression of important cell surface suppressive molecules such as cytotoxic T lymphocyte antigen-4 and programmed death-1 that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Regulatory T cells and particularly IL-10 also have an influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies. In addition, development of allergen-specific B regulatory cells that produce IL-10 and develop into IgG4 producing plasma cells represent essential players in peripheral tolerance. These findings together with the new biotechnological approaches create a platform for development of the advanced vaccines. Moreover, reliable biomarkers could be selected and validated with the intention to select the patients who will benefit most from this immune-modifying treatment. Thus, allergen-SIT could provide a complete cure for a larger number of allergic patients and novel preventive approaches need to be elaborated.     

皮下注射标准化屋尘螨变应原疫苗治疗支气管哮喘和（或）变应性鼻炎的速发不良反应

摘要：目的分析应用标准化屋尘螨变应原对变应性哮喘和（或）变应性鼻炎进行皮下特异性免疫治疗（subcutaneous specific immunotherapy,SCIT）的速发不良反应。方法回顾性记录广州医科大学附属第一医院变态反应科2004年11月至2012年5月对屋尘螨过敏的哮喘和（或）变应性鼻炎患者接受SCIT过程中出现的速发不良反应,并分析速发不良反应与注射剂量、患者年龄、性别、患病种类和变态反应程度的关系。结果研究共纳入462例患者,其中452例（97．8％）出现速发局部不良反应,153例（33．1％）出现速发全身不良反应;所有患者共接受15645针次皮下注射,其中8523针次（54．5％）出现速发局部不良反应,397针次（2．5％）出现速发全身不良反应。速发局部不良反应发生率随剂量增加而增高,而速发全身不良反应主要分布在剂量上升阶段（2000～80000 SQU）。单纯哮喘及哮喘合并变应性鼻炎的速发不良反应（局部和全身）的发生率高于单纯变应性鼻炎（P〈0．01）。儿童速发局部不良反应发生率高于成人（P〈0．001）,但速发全身不良反应的发生率在儿童及成人患者间差异无统计学意义（P〉0．05）。儿童患者中,男性速发不良反应发生率高于女性（P〈0．01）;而在成人患者中,女性速发不良反应发生率高于男性（P〈0．01）。速发不良反应（局部和全身）的发生率随着屋尘螨特异性IgE级别的增高而升高（P〈0．001）;在皮下注射过程中出现速发全身不良反应者治疗前总IgE[（634．24±883．91）U／ml]与未发生速发全身不良反应者治疗前总IgE[（416．60±438．59）U／ml]比较,差异有统计学意义（t=2．008,P=0．048）。结论对屋尘螨过敏的哮喘和（或）变应性鼻炎患者进行标准化屋尘螨变应原的SCIT时,速发局部不良反应常见,而速发全身不良反应少见,哮喘和鼻炎合并哮喘、少年男性、成年女性及屋尘螨特异性IgE和总IgE水平较高时,速发不良反应的发生率增高,且随注射变应原剂量递增而存在增高趋势,剂量快速上升阶段应警惕严重不良反应的发生。     

特异性免疫治疗在特应性皮炎中的应用

特异性免疫治疗（SIT）是唯一可能改变变应性疾病自然病程的治疗方法，SIT对IgE介导的变应性鼻炎和变应性哮喘的疗效已经得到公认，但对特应性皮炎（AD）的应用价值却一直存在争论。造成这种争议的原因可能与不同研究所使用的变应原类别、治疗方案、治疗疗程、评价临床疗效的标准以及有无环境控制和所用对症药物之间的差别有关。本文对近年来有关SIT在AD中的应用进行综述。