BACKGROUND & AIMS: :Bacteria utilize quorum-sensing systems to modulate environmental stress responses. The quorum-sensing system of Streptococcus mutans is mediated by the competence-stimulating peptide (CSP), whose precursor is encoded by the comC gene. A comC mutant of strain GS5 exhibited enhanced antimicrobial sensitivity to a wide variety of different agents. Since the addition of exogenous CSP did not complement this phenotype, it was determined that the increased tetracycline, penicillin, and triclosan sensitivities resulted from repression of the putative bacteriocin immunity protein gene, bip, which is located immediately upstream from comC. We further demonstrated that the inactivation of bip or smbG, another bacteriocin immunity protein gene present within the smb operon in S. mutans GS5, affected sensitivity to a variety of antimicrobial agents. Furthermore, both the bip and smbG genes were upregulated in the presence of low concentrations of antibiotics and were induced during biofilm formation relative to in planktonic cells. These results suggest, for the first time, that the antimicrobial sensitivity of a bacterium can be modulated by some of the putative bacteriocin immunity proteins expressed by the organism. The implications of these observations for the evolution of bacteriocin immunity protein genes as well as for potential new chemotherapeutic strategies are discussed.

背景与目标： ：细菌利用群体感应系统来调节环境应激反应。变异链球菌的群体感应系统由能力刺激肽（CSP）介导，其前体由comC基因编码。菌株GS5的comC突变体对多种不同的药物表现出增强的抗菌敏感性。由于外源CSP的添加不能补充该表型，因此确定增加的四环素，青霉素和三氯生敏感性是由推定的细菌素免疫蛋白基因bip抑制而来的，该基因位于comC的上游。我们进一步证明了bip或smbG（变形链球菌GS5的smb操纵子内存在的另一种细菌素免疫蛋白基因）的失活影响了对多种抗菌剂的敏感性。此外，在低浓度抗生素存在下，bip和smbG基因均被上调，并且在生物膜形成过程中相对于浮游细胞被诱导。这些结果首次表明，细菌的抗菌敏感性可以由生物体表达的某些假定的细菌素免疫蛋白来调节。讨论了这些观察结果对细菌素免疫蛋白基因的进化以及潜在的新化学治疗策略的影响。

BACKGROUND & AIMS: :Protection against intracellular pathogens or tumor antigens requires T-cell mediated responses. Recently, it has become apparent that protection against disease correlates with T cells of the central memory type in many instances. Here, we analyze current data to distill a set of rules for the induction and maintenance of central memory T-cell responses. Recent studies show that T-cell help and the lack of overt inflammation at the time of priming are prerequisite for the induction, maintenance and expansion of memory T cells. Central to our hypothesis is that, in addition to these factors, successful vaccination in the immunologically inexperienced individual should be based on low antigen dose, to decelerate replicative senescence in responding cells and favor lineage differentiation of central memory T cells. In the immunologically experienced individual, it will be necessary, in addition, to abate the antigen load in plasma before vaccination. These guiding principles might help to raise improved protective T-cell responses by vaccination in humans.

背景与目标： ：对细胞内病原体或肿瘤抗原的保护需要T细胞介导的反应。最近，很明显，在许多情况下，针对疾病的保护与中央记忆型T细胞相关。在这里，我们分析当前数据以提炼出一套诱导和维持中央记忆T细胞反应的规则。最近的研究表明，在引发时，T细胞的帮助和缺乏明显的炎症是诱导，维持和扩展记忆T细胞的先决条件。我们假说的中心在于，除这些因素外，对免疫缺乏经验的个体进行的成功疫苗接种应基于低抗原剂量，以减慢应答细胞中的复制衰老并有利于中央记忆T细胞的谱系分化。对于具有免疫学经验的个人，此外，有必要在接种疫苗之前减轻血浆中的抗原负荷。这些指导原则可能有助于通过接种疫苗来提高保护性T细胞反应。

BACKGROUND & AIMS: :To assess the effect of the Expanded Program on Immunization (EPI) in rural Africa, blood samples were collected in two Kenyan sublocations. Serum antibodies against tetanus toxoid were measured in 155 individuals 1-70 years of age. Titers greater than the protective level of 0.01 IU/ml were found in 47% of the population. Protection was significantly higher in children born after the launching of the EPI (68%) and in women who had been at childbearing age since then (69%). Significantly lower protection was demonstrated in other age and sex-groups. The level of protection in children was equal in the two populations, whereas protection in fertile women was significantly lower in the population living a long distance from a health center. Diphtheria anti-toxin was measured in the samples from one sublocation, and 70 of 84 individuals (83%) had antibody levels greater than the protective level. No age or sex difference could be found, and there was no correlation between response levels to diphtheria and tetanus. This implicates natural infections as an important source of diphtheria antibodies. Our findings demonstrate a need for better coverage of the adult population against tetanus. Furthermore, diphtheria transmission still appears to take place, underscoring the importance of diphtheria vaccination of travelers to rural Africa.

背景与目标： ：为了评估非洲农村地区免疫扩展计划（EPI）的效果，在两个肯尼亚子地区采集了血液样本。在1-5个1至70岁的个体中测量了抗破伤风类毒素的血清抗体。在47％的人口中发现的滴度大于0.01 IU / ml的保护水平。 EPI启动后出生的孩子（68％）和此后达到育龄的妇女（69％）的保护水平明显更高。在其他年龄段和性别组中，保护作用明显降低。在这两个人口中，儿童的保护水平是相同的，而在距卫生所很远的人口中，生育妇女的保护水平要低得多。在一个分区中的样品中测量了白喉抗毒素，在84个人中有70个人（83％）的抗体水平高于保护水平。没有发现年龄或性别差异，并且对白喉和破伤风的反应水平之间没有相关性。这暗示自然感染是白喉抗体的重要来源。我们的发现表明，需要更好地覆盖破伤风的成年人群。此外，白喉传播仍在发生，强调了前往非洲农村的旅行者接种白喉疫苗的重要性。

BACKGROUND & AIMS: :Neutralizing antibody titers of 47 infants whose mothers sustained measles (measles group) and 70 whose mothers were vaccinated (vaccine group) were compared at birth, 4 and 8 months of age. All children had antibodies at birth and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15% in the vaccine group (P < 0.001). The geometric mean titers were significantly lower in the vaccine group than in the measles group and the difference corresponded to the antibody loss occurring in only 1.5 months of life. This small difference may reflect past exposure to wild virus of many vaccinated mothers.

背景与目标： ：比较出生时，4和8个月时母亲麻疹的47例婴儿（麻疹组）和母亲疫苗接种的70例（疫苗组）的中和抗体滴度。所有儿童在出生时均具有抗体，在4个月时具有88％的抗体。在8个月时，麻疹组中有49％的抗体，疫苗组中有15％（P <0.001）。疫苗组的几何平均滴度显着低于麻疹组，差异对应于仅1.5个月生命中发生的抗体损失。这个很小的差异可能反映了许多接种过疫苗的母亲过去接触野生病毒的情况。

BACKGROUND & AIMS: :Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic patients and experimental animals display a "deactivated" phenotype, characterized by impaired inflammatory and antimicrobial responses, including hyporesponsiveness to LPS. We investigated the role of the LPS/TLR4 axis and its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), in modulating the immunosuppression of sepsis using a murine model of peritonitis-induced sepsis followed by secondary challenge by intratracheal Pseudomonasaeruginosa. Septic mice demonstrated impaired alveolar macrophage function and increased mortality when challenged with intratracheal Pseudomonas as compared with nonseptic controls. TLR2 and TLR4 expression was unchanged in the lung following sepsis, whereas levels of IRAK-M were upregulated. Macrophages from IRAK-M-deficient septic mice produced higher levels of proinflammatory cytokines ex vivo and greater costimulatory molecule expression in vivo as compared with those of their WT counterparts. Following sepsis and secondary intrapulmonary bacterial challenge, IRAK-M(-/-) animals had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice. In addition, increased pulmonary chemokine and inflammatory cytokine production was observed in IRAK-M(-/-) animals, leading to enhanced neutrophil recruitment to airspaces. Collectively, these findings indicate that IRAK-M mediates critical aspects of innate immunity that result in an immunocompromised state during sepsis.

背景与目标： ：败血症导致相对免疫抑制状态，使重症患者容易受到继发感染并增加死亡率。从败血病患者和实验动物中分离出的单核细胞表现出“失活”表型，其特征是炎症和抗菌反应减弱，包括对LPS的反应不足。我们调查了LPS / TLR4轴及其抑制剂IL-1受体相关激酶-M（IRAK-M）在调节败血症的免疫抑制中的作用，该模型使用的是腹膜炎诱导的败血症的鼠模型，随后是气管内继发性攻击铜绿假单胞菌。与非败血性对照相比，经气管内假单胞菌攻击时，败血性小鼠肺泡巨噬细胞功能受损，死亡率增加。败血症后肺中TLR2和TLR4表达未改变，而IRAK-M水平上调。与野生型WT小鼠相比，IRAK-M缺陷型败血症小鼠的巨噬细胞离体产生更高水平的促炎细胞因子，体内产生更高的共刺激分子表达。败血症和继发性肺内细菌攻击后，与WT小鼠相比，IRAK-M（-/-）动物具有更高的存活率并改善了从肺和血液中的细菌清除率。此外，IRAK-M（-/-）动物中观察到增加的肺趋化因子和炎性细胞因子的产生，导致嗜中性粒细胞向空域的募集增加。总的来说，这些发现表明IRAK-M介导了先天免疫的关键方面，这些固有方面在败血症期间导致免疫功能低下。

BACKGROUND & AIMS: Mice which have recovered from Babesia microti infection lose their parasitaemia as soon as three weeks after recovery and become solidly immune. This sterile immunity is not affected by splenectomy and may last for the life of the mouse. Mice which have recovered from B. hylomysci infection continue to harbour parasites at a subpatent level and spontaneous relapses were common after recovery. Hence the type of immunity which developed against this parasite is premunition and may last for life. Such immunity was not absolute and considerable parasitaemias developed after challenge. Cross-protection occurred between the two species of parasite.

背景与目标： 从巴氏杆菌微量感染中恢复过来的小鼠在恢复后三周之内就失去了寄生虫血症，并具有牢固的免疫力。这种无菌免疫不受脾切除术的影响，并且可以持续小鼠的一生。从hypoyysci感染中恢复的小鼠继续在亚专利水平上携带寄生虫，并且恢复后自发复发很常见。因此，针对这种寄生虫而产生的免疫力类型是弹药，可能会持续一生。这种免疫力不是绝对的，在攻击后会产生大量的寄生虫病。两种寄生虫之间发生交叉保护。

BACKGROUND & AIMS: :We conducted a prospective study of 60 patients in a tertiary care referral center to ascertain the status of cell-mediated immunity as determined by delayed hypersensitivity reactions in patients with nasopharyngeal carcinoma (NPC) or allergic rhinitis. Delayed hypersensitivity as detected by Mantoux testing is generally accepted as a reflection of the level of cell-mediated immunoactivity-the less hypersensitivity reaction that occurs, the lower the level of immunoactivity is, and vice versa. Our study population was made up of three groups: 20 newly diagnosed patients with NPC (pretreatment), 20 age- and sex-matched patients with allergic rhinitis, and 20 matched controls without either disease. A negative Mantoux test (0- to 5-mm induration) was seen in 13 patients with NPC (65.0%), in 17 patients with allergic rhinitis (85.0%), and in 16 controls (80.0%); none of these differences was statistically significant. However, it is interesting that while the NPC group had the lowest percentage of negative Mantoux results overall, it had the highest percentage of patients who had no reaction at all (i.e., 0-mm induration); a complete absence of any reaction was seen in 7 of the 13 Mantoux-negative NPC patients (53.8%), compared with 2 of the 17 Mantoux-negative allergic rhinitis patients (11.8%) and 3 of the 16 Mantoux-negative controls (18.8%). An absence of a reaction generally indicates a very limited degree of cell-mediated immunoactivity. Therefore, we conclude that patients with NPC appear to have significantly less cell-mediated immunity than do patients with allergic rhinitis and normal controls; no statistically significant difference was noted between the latter two groups.

背景与目标： ：我们在三级医疗转诊中心对60例患者进行了一项前瞻性研究，以确定由鼻咽癌（NPC）或变应性鼻炎患者的迟发性超敏反应确定的细胞介导的免疫状态。通过Mantoux测试检测到的迟发型超敏反应通常被认为是细胞介导的免疫活性水平的反映-发生的超敏反应越少，免疫活性水平就越低，反之亦然。我们的研究人群由三组组成：20名新诊断的NPC（预处理）患者，20名年龄和性别匹配的变应性鼻炎患者以及20个无任何疾病的匹配对照组。在13例NPC患者（65.0％），17例过敏性鼻炎患者（85.0％）和16例对照（80.0％）中，Mantoux试验阴性（硬结度为0至5mm）。这些差异均无统计学意义。然而，有趣的是，尽管NPC组的总体Mantoux阴性结果百分比最低，但完全没有反应（即硬结0毫米）的患者比例最高。 13名Mantoux阴性NPC患者中有7名完全没有反应（53.8％），而17名Mantoux阴性变应性鼻炎患者中有2名（11.8％）和16名Mantoux阴性对照中有3名（18.8） ％）。不存在反应通常表明细胞介导的免疫活性非常有限。因此，我们得出结论，与变应性鼻炎和正常对照组相比，NPC患者似乎具有明显更少的细胞介导的免疫力。后两组之间没有统计学上的显着差异。

BACKGROUND & AIMS: :The definition of immune correlates of protection in HIV-1 infection is pivotal to the design of successful vaccine candidates and strategies. Although significant methodological and conceptual strides have been made in our understanding of HIV-specific cellular immunity, we have not yet defined those parameters that have a role in controlling the spread of HIV infection. This review discusses the basis of our understanding of HIV-specific cellular immunity and identifies its shortcomings. Furthermore, potential protective characteristics will be proposed that may ultimately be required for an effective vaccine designed to stimulate cellular immunity against HIV-1.

背景与目标： ：在HIV-1感染中保护性免疫相关因子的定义对于成功的候选疫苗和策略的设计至关重要。尽管在了解HIV特异性细胞免疫方面取得了重大的方法和概念上的进步，但我们尚未定义那些在控制HIV感染扩散中起作用的参数。这篇综述讨论了我们对HIV特异性细胞免疫理解的基础，并指出了它的缺点。此外，将提出潜在的保护性特征，这些潜在的保护性特征最终可能是设计用于刺激针对HIV-1的细胞免疫的有效疫苗所必需的。

BACKGROUND & AIMS: :Cellular exudates induced by infusion with helminth antigens were examined in non-lactating mammary glands of ewes immune to infection with the abomasal nematode, Haemonchus contortus. Secondary immunological responsiveness was expressed in two ways. Firstly, antigens from adult H. contortus elicited larger eosinophil-rich cellular exudates in immune compared to non-immune ewes. In this situation, secondary responsiveness in the mammary gland must have been generated through abomasal infection with the parasite. Secondly, repeated infusion with the antigens from adult H. contortus increased the size of cellular exudates in both immune and non-immune ewes. Eosinophils predominated but numbers of macrophages and lymphocytes were also increased. In this second situation, secondary responsiveness must have been either supplemented in immune ewes or derived completely in non-immune ewes by contact with helminth antigens through the mammary gland. The helminth antigens which induce eosinophil exudates in the mammary gland may not be potently protective against H. contortus. Furthermore, eosinophil exudation may not be an in vivo correlate of immunity which is directly useful for discriminating protective antigens and applicable to vaccine development. Infusion with antigens from adult forms of either H. contortus or Trichostrongylus colubriformis elicited cellular exudates equally well in immune ewes primed by infusion with H. contortus adult antigens 7 days beforehand. In addition, antigens from infective larvae of H. contortus elicited cellular exudates more potently than antigens from adult worms. However, vaccination with irradiated larvae has shown that species-specific protective immunity for H. contortus is stronger than cross-protective immunity conferred by T. colubriformis.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： ：在非泌乳性母羊的乳腺中检查了通过注入蠕虫抗原诱导的细胞渗出液，该母乳对原虫线虫Haemonchus contortus的感染免疫。继发性免疫应答以两种方式表达。首先，与非免疫母羊相比，来自成年H. contortus的抗原在免疫中引起较大的富含嗜酸性粒细胞的细胞分泌物。在这种情况下，乳腺的继发性反应一定是通过寄生虫的寄生虫感染而产生的。其次，反复输注来自成年弯曲杆菌的抗原会增加免疫母羊和非免疫母羊中细胞渗出液的大小。嗜酸性粒细胞占主导，但巨噬细胞和淋巴细胞的数量也增加。在第二种情况下，必须通过免疫母羊与蠕虫抗原接触，在免疫母羊中补充次级反应性，或者在非免疫母羊中完全衍生出次级反应性。在乳腺中诱导嗜酸性粒细胞渗出液的蠕虫抗原可能无法有效地抵抗捻转嗜血杆菌。此外，嗜酸性粒细胞渗出可能不是免疫的体内相关性，其直接用于区分保护性抗原并且可用于疫苗开发。输注来自成人的Con。contortus或Trichostrongylus colubriformis的抗原，在7天前输注Contortus的成年抗原引发的免疫母羊中，细胞渗出液的效果相同。另外，与来自成虫的抗原相比，来自扭曲嗜血杆菌的幼虫的抗原更有效地引起细胞渗出液。然而，用辐照过的幼虫进行的疫苗接种已表明，对棉铃虫的物种特异性保护性免疫力比colubriformis赋予的交叉保护性免疫力强（摘要截短为250字）。

BACKGROUND & AIMS: :Auto-anti-idiotypic mechanisms can regulate the protective immune response against Schistosoma mansoni. Anti-idiotypic responses were stimulated by immunization of mice either with nonspecifically induced lymphoblasts, produced with Con A, or with Ag-induced lymphoblasts bearing specific idiotypic receptors. The effect of the induced anti-idiotypic response upon clonotypic cellular reactivity was assessed in vitro through the suppression of antigen-mediated blast transformation by cloned T cells and in vivo by suppression of resistance to S. mansoni and delayed-type hypersensitivity responses against specific Ag. Differential regulation of humoral immune responses was studied at the levels of specific epitopic recognition, the expression of specific Id, and the production of anti-idiotypic responses directed against mAb bearing specific Id. Anti-idiotypic sensitization resulted in variable (10 to 90%) suppression of the immune response to discrete antigenic epitopes, the expression of specific idiotypic phenotypes, and anti-idiotypic, antiparatopic responses against T cell clonotypes and antibody idiotypic phenotypes. In vitro admixture and in vivo challenge studies resulted in consonant differential suppression. Thus idiotypic regulation can mold the fine specificities of the protective immune response to S. mansoni at the clonal level and may provide an approach to optimize the expression and assessment of resistance.

背景与目标： 自动抗独特型机制可以调节针对曼氏血吸虫的保护性免疫反应。通过用Con A产生的非特异性诱导的淋巴母细胞，或用Ag诱导的携带特定独特型受体的淋巴母细胞免疫小鼠，可以刺激抗独特型应答。在体外通过抑制克隆的T细胞对抗原介导的胚泡转化的抑制来评估诱导的抗独特型反应对克隆型细胞反应性的影响，并在体内通过抑制对曼氏沙门氏菌的抗性和针对特定Ag的迟发型超敏反应来评估体内诱导的抗独特型反应的作用。 。研究了在特定表位识别，特定Id的表达以及针对带有特定Id的mAb的抗独特型反应水平上的体液免疫应答的差异调节。抗独特型致敏作用导致对离散抗原表位的免疫反应，特异性独特型表型的表达以及针对T细胞克隆型和抗体独特型表型的抗独特型，抗副反应的变化受到抑制（10％至90％）。体外混合和体内攻击研究导致辅音差异抑制。因此，独特型调节可以在克隆水平上塑造对曼氏链球菌的保护性免疫应答的优良特异性，并且可以提供优化抗性表达和评估的方法。

BACKGROUND & AIMS: :In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels. FLNA did not show the same results. The HLA-DR-presented GNS peptide has marked sequence homology with epitopes from sulfatase proteins of the Prevotella sp. and Parabacteroides sp., whereas the HLA-DR-presented FLNA peptide has homology with epitopes from proteins of the Prevotella sp. and Butyricimonas sp., another gut commensal. Patients with T cell reactivity with each self-peptide also had responses to the corresponding microbial peptides, and the levels were directly correlated. Furthermore, HLA-DR molecules encoded by shared-epitope (SE) alleles were predicted to bind these self- and microbial peptides strongly, and these responses were more common in RA patients with SE alleles. Thus, sequence homology between T cell epitopes of 2 self-proteins and a related order of gut microbes may provide a link between mucosal and joint immunity in patients with RA.

背景与目标： 在类风湿关节炎（RA）中，粘膜部位（如肠道菌群）的免疫触发可能会促进影响关节的自身免疫。在这里，我们使用基于发现的蛋白质组学来检测滑膜或外周血单核细胞中HLA-DR呈递的肽，并鉴定了2种自身抗原N-乙酰氨基葡萄糖-6-硫酸酯酶（GNS）和纤维蛋白A（FLNA）作为T和T的靶标B细胞反应分别在52％和56％的RA患者中发生。 GNS和FLNA在滑膜中均高表达。 GNS似乎是瓜氨酸化的，并且GNS抗体值与抗瓜氨酸化的蛋白抗体（ACPA）的水平相关。 FLNA没有显示相同的结果。 HLA-DR呈递的GNS肽与Prevotella sp的硫酸酯酶蛋白的表位具有明显的序列同源性。 HLA-DR呈递的FLNA肽与Prevotella sp。蛋白的表位具有同源性。和Butyricimonas sp。，另一个肠胃奖。与每种自身肽具有T细胞反应性的患者也对相应的微生物肽有反应，并且其水平直接相关。此外，预计由共享表位（SE）等位基因编码的HLA-DR分子会强烈结合这些自身和微生物肽，这些反应在SE等位基因的RA患者中更为常见。因此，两种自身蛋白的T细胞表位与肠道微生物相关顺序之间的序列同源性可能为RA患者的粘膜免疫和关节免疫之间提供了联系。

BACKGROUND & AIMS: PROBLEM:To evaluate the site-specific immunoregulatory mechanisms against bacterial infection in the human fallopian tubes. METHOD OF STUDY:We investigated the effects of lipopolysaccharide (LPS) on the production of CXC chemokines by cultured oviductal epithelial cells (OEC) and oviductal stromal fibroblasts (OSF). The expression of Toll-like receptor (TLR) 4 and CD14 protein in OEC and OSF were evaluated. The phosphorylation of the inhibitor kappaB-alpha (IkappaB-alpha) protein after LPS stimulation was also examined. RESULTS:Lipopolysaccharide stimulated the secretion of granulocyte chemotactic protein-2, growth-regulated oncogene-alpha, and epithelial neutrophil activating peptide-78 by OSF, but not by OEC. The phosphorylation of the IkappaB-alpha protein was not detected in OEC after stimulation by LPS, whereas IkappaB-alpha phosphorylation was observed in OSF after stimulation by LPS. The expression of the TLR4 protein and mRNA was detected only in OSF but not in OEC. The expression of CD14 was not detected in either OEC or OSF. CONCLUSION:These results suggest that epithelial cells and fibroblasts in the human fallopian tube have evolved a unique, site-specific mechanism for recognizing Gram-negative pathogens. The lack of TLR4 in OEC may be important for avoiding a state of unnecessary inflammation that could disrupt the epithelial barrier and cause irreversible tubal scarring.

背景与目标： 问题：评估针对人类输卵管细菌感染的特定部位免疫调节机制。
研究方法：我们研究了脂多糖（LPS）对培养的输卵管上皮细胞（OEC）和输卵管间质成纤维细胞（OSF）产生CXC趋化因子的影响。评估了Toll样受体（TLR）4和CD14蛋白在OEC和OSF中的表达。还检查了LPS刺激后抑制剂kappaB-alpha（IkappaB-alpha）蛋白的磷酸化。
结果：脂多糖通过OSF刺激了粒细胞趋化蛋白2的分泌，生长调节的癌基因α和上皮中性粒细胞活化肽78的分泌，而OEC则没有。 LPS刺激后在OEC中未检测到IkappaB-α蛋白的磷酸化，而LPS刺激后在OSF中观察到了IkappaB-α磷酸化。仅在OSF中检测到TLR4蛋白和mRNA的表达，而在OEC中未检测到。在OEC或OSF中均未检测到CD14的表达。
结论：这些结果表明，人输卵管中的上皮细胞和成纤维细胞已发展出一种独特的，针对特定部位的机制来识别革兰氏阴性病原体。 OEC中TLR4的缺乏对于避免不必要的炎症状态可能很重要，这种炎症可能会破坏上皮屏障并导致不可逆的输卵管瘢痕形成。

BACKGROUND & AIMS: :Despite its potency, the wider use of immunotherapy for B cell malignancies is hampered by the lack of well-defined tumor-specific Ags. In this study, we demonstrate that an evolutionarily conserved 37-kDa immature laminin receptor protein (OFA-iLRP), a nonimmunogenic embryonic Ag expressed by a variety of tumors, is rendered immunogenic if targeted to the APCs using the CCR6 ligands MIP3alpha/CCL20 and mDF2beta. The CCR6 targeting facilitated efficient Ag cross-presentation and induction of tumor-neutralizing CTLs. Although the Ag targeting alone, without activation of dendritic cells (DCs), is proposed to induce tolerance, and MIP3alpha does not directly activate DCs, the MIP3alpha-based vaccine efficiently induced protective and therapeutic antitumor responses. The responses were as strong as those elicited by the OFA-iLRP fusions with moieties that activated DCs and Th1-type cytokine responses, mDF2beta, or mycobacterial Hsp70 Ag. Although the same cDNA encodes the dimerized high-affinity mature 67-kDa mLRP that is expressed in normal tissues to stabilize the binding of laminin to cell surface integrins, the vaccines expressing OFA-iLRP elicited long-term protective CD8(+) T cell-mediated memory responses against syngeneic B cell lymphoma, indicating the potential application of these simple vaccines as preventive and therapeutic formulations for human use.

背景与目标： ：尽管缺乏效力，但缺乏明确的肿瘤特异性Ags阻碍了B细胞恶性肿瘤免疫治疗的广泛应用。在这项研究中，我们证明，如果使用CCR6配体MIP3alpha / CCL20和APC靶向APC，则进化上保守的37 kDa不成熟层粘连蛋白受体蛋白（OFA-iLRP）（一种由多种肿瘤表达的非免疫原性胚胎Ag）具有免疫原性。 mDF2beta。 CCR6靶向促进了有效的Ag交叉呈递和肿瘤中和性CTL的诱导。尽管有人提出仅将Ag靶向而不激活树突状细胞（DCs）来诱导耐受性，并且MIP3alpha不能直接激活DCs，但是基于MIP3alpha的疫苗有效地诱导了保护性和治疗性抗肿瘤反应。响应与由激活DC和Th1型细胞因子响应，mDF2beta或分枝杆菌Hsp70 Ag的部分的OFA-iLRP融合引发的响应一样强。尽管相同的cDNA编码在正常组织中表达的二聚化高亲和力成熟67-kDa mLRP，以稳定层粘连蛋白与细胞表面整联蛋白的结合，但表达OFA-iLRP的疫苗引起了CD8（）T细胞介导的长期保护作用对同源B细胞淋巴瘤的记忆反应，表明这些简单疫苗作为人类预防和治疗制剂的潜在应用。

BACKGROUND & AIMS: :Innate immunity comprises evolutionarily conserved self-defense mechanisms against microbial infections. In mammals, innate immunity interacts with adaptive immunity and has a key role in the regulated immune response. Therefore, innate immunity is a pharmaceutical target for the development of immune regulators. Using Drosophila ex vivo culture systems, we isolated a cyclopentanediol analogue from Aspergillus sp. as an immunosuppressive substance. This compound selectively suppressed activation of the IMD pathway in Drosophila in vivo and the target molecules of the compound lie between the Imd adaptor protein and dTAK1 kinase in the IMD pathway. In human cells, the compound suppressed TNF-alpha, but not IL-1beta, stimulation-induced activation of NF-kappaB, suggesting that its target molecules are upstream of TAK1 in mammalian innate immunity.

背景与目标： ：天然免疫包括针对微生物感染的进化保守的自卫机制。在哺乳动物中，先天免疫与适应性免疫相互作用，并且在调节的免疫反应中起关键作用。因此，先天免疫是开发免疫调节剂的药物靶标。使用果蝇离体培养系统，我们从曲霉菌中分离出环戊二醇类似物。作为一种免疫抑制物质。该化合物在体内果蝇中选择性地抑制了IMD途径的激活，该化合物的目标分子位于IMD途径中的Imd衔接子蛋白和dTAK1激酶之间。在人类细胞中，该化合物抑制TNF-α刺激，但不能抑制IL-1beta刺激诱导的NF-κB活化，表明其靶分子在哺乳动物先天免疫中位于TAK1上游。

BACKGROUND & AIMS: :The effect of age on the humoral response to Porphyromonas gingivalis was assessed in groups of adults (25 to 54 years and 55 to 74 years) with periodontal disease and compared with that in age-matched healthy controls. To determine whether there was an antibody response against P. gingivalis, we measured serum antibodies against whole cells of P. gingivalis 381, A7A1-28, and W50. In addition, antibody levels against purified P. gingivalis outer membrane proteins (i.e., the 43-kDa fimbrial protein and a 75-kDa protein) were also evaluated. Elderly subjects showed the same response to P. gingivalis as younger subjects. Immunoglobulin G (IgG) antibodies to both purified proteins were also elevated in both diseased groups as compared with the normal groups. Total serum IgG, IgA, and IgM levels were also determined by an enzyme-linked immunosorbent assay for all four groups. Total serum IgG levels were elevated in older adults with periodontitis and total IgA levels were elevated in both groups of older adults compared with the younger groups of similar disease status. Total serum IgM levels were comparable for the four groups. Antinuclear antibody titers were assessed in the two groups of older adults and were also found to be higher for the group with periodontitis. These studies show that older adults as well as younger adults have markedly elevated specific antibodies of the IgG and IgA classes to antigens of P. gingivalis, a putative pathogen in both groups. Furthermore, older adults with periodontitis have significantly elevated levels of total serum IgG which may possibly be related to higher levels of autoantibodies.

背景与目标： ：在患有牙周疾病的成年人（25至54岁和55至74岁）组中评估了年龄对牙龈卟啉单胞菌体液反应的影响，并与年龄相匹配的健康对照组进行了比较。为了确定是否存在针对齿龈假单胞菌的抗体应答，我们测量了针对齿龈假单胞菌381，A7A1-28和W50的全细胞的血清抗体。另外，还评估了针对纯化的牙龈卟啉单胞菌外膜蛋白（即43-kDa纤维蛋白和75-kDa蛋白）的抗体水平。老年受试者对牙龈卟啉单胞菌的反应与年轻受试者相同。与正常组相比，在两个患病组中针对两种纯化蛋白的免疫球蛋白G（IgG）抗体也均升高。血清IgG，IgA和IgM的总含量也通过酶联免疫吸附法测定了所有四个组。与患有类似疾病的年轻人群相比，患有牙周炎的老年人的总血清IgG水平升高，两组成年人的总IgA水平均升高。四组的总血清IgM水平相当。在两组老年人中评估了抗核抗体的效价，并且发现牙周炎组的抗核抗体效价更高。这些研究表明，成年人和年轻人对牙龈卟啉单胞菌抗原（两组中均假定的病原体）的IgG和IgA类特异性抗体明显升高。此外，患有牙周炎的老年人的血清总IgG水平明显升高，这可能与自身抗体水平升高有关。