Functional innervation of hepatic iNKT cells is immunosuppressive following stroke

Systemic immunosuppression has been associated with stroke for many years, but the underlying mechanisms are poorly understood. In this study, we demonstrated that stroke induced profound behavioral changes in hepatic invariant NKT (iNKT) cells in mice. Unexpectedly, these effects were mediated by a noradrenergic neurotransmitter rather than a CD1d ligand or other well-characterized danger signals. Blockade of this innervation was protective in wild-type mice after stroke but had no effect in mice deficient in iNKT cells. Selective immunomodulation of iNKT cells with a specific activator (α-galactosylceramide) promoted proinflammatory cytokine production and prevented infections after stroke. Our results therefore identify a molecular mechanism that leads to immunosuppression after stroke and suggest an attractive potential therapeutic alternative to antibiotics, namely, immunomodulation of iNKT cells to prevent stroke-associated infections.     

Coordination of early protective immunity to viral infection by regulatory T cells

Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue.     

The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota

Mucosal surfaces constantly encounter microbes. Toll-like receptors (TLRs) mediate recognition of microbial patterns to eliminate pathogens. By contrast, we demonstrate that the prominent gut commensal Bacteroides fragilis activates the TLR pathway to establish host-microbial symbiosis. TLR2 on CD4(+) T cells is required for B. fragilis colonization of a unique mucosal niche in mice during homeostasis. A symbiosis factor (PSA, polysaccharide A) of B. fragilis signals through TLR2 directly on Foxp3(+) regulatory T cells to promote immunologic tolerance. B. fragilis lacking PSA is unable to restrain T helper 17 cell responses and is defective in niche-specific mucosal colonization. Therefore, commensal bacteria exploit the TLR pathway to actively suppress immunity. We propose that the immune system can discriminate between pathogens and the microbiota through recognition of symbiotic bacterial molecules in a process that engenders commensal colonization.     

玉米秸秆发酵垫料微生物对小鼠免疫功能的影响

 【目的】以小白鼠为实验动物模型、玉米秸秆为发酵床垫料,探讨发酵床垫料中的微生物对小鼠机体免疫功能的影响。【方法】将小鼠随机分为4组,第1—3组小鼠分别置于用不同微生物配方发酵的玉米秸秆垫料中饲养,第4组作为对照组,放入未发酵的垫料中饲喂。期间检测小鼠血清中的抗体效价、IL-4和IFN-γ的含量,血液中白细胞总数、淋巴细胞数量、红细胞总数及小鼠盲肠内乳酸菌数量,抗疲劳游泳时间等指标。【结果】发酵垫料组微生物能显著提高小鼠抗体效价和血液中红细胞数量、血红蛋白浓度及盲肠乳酸菌数量（P＜0.05）;可增加血清中IFN-γ、IL-4含量和血液中白细胞总数、淋巴细胞数量,差异不显著（P＞0.05）;抗疲劳试验结果表明,发酵垫料微生物能显著延长小鼠的游泳时间（P＜0.05）。【结论】玉米秸秆发酵垫料微生物可显著提高动物体的免疫功能及健康状况。     

A critical role for eosinophils in allergic airways remodeling

Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness and mucus secretion were similar to those observed in wild-type mice, but eosinophil-deficient mice were significantly protected from peribronchiolar collagen deposition and increases in airway smooth muscle. These data suggest that eosinophils contribute substantially to airway remodeling but are not obligatory for allergen-induced lung dysfunction, and support an important role for eosinophil-targeted therapies in chronic asthma.     

Defining a link with asthma in mice congenitally deficient in eosinophils

Eosinophils are often dominant inflammatory cells present in the lungs of asthma patients. Nonetheless, the role of these leukocytes remains poorly understood. We have created a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells. Allergen challenge of PHIL mice demonstrated that eosinophils were required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma. The development of an eosinophil-less mouse now permits an unambiguous assessment of a number of human diseases that have been linked to this granulocyte, including allergic diseases, parasite infections, and tumorigenesis.     

Prostaglandin D2 as a mediator of allergic asthma

Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.     

传染性法氏囊病疫苗免疫种鸡后子代雏鸡的免疫学变化

应用现代免疫学新技术对传染性法氏囊病 (IBD)疫苗免疫种鸡后 ,其子代雏鸡外周血液和免疫器官组织的免疫学变化进行了动态研究。结果发现 :传染性法氏囊病疫苗免疫种鸡后 ,其子代雏鸡外周血液 T、B细胞数量和 Ig G,Ig M,Ig A含量及免疫器官组织的 T细胞、Ig G,Ig M,Ig A抗体生成细胞数量均不同程度地高于未免疫的相应对照雏鸡 ,表明 IBD疫苗免疫母鸡后 ,子代雏鸡外周血液和免疫器官组织的体液免疫和细胞免疫功能明显增强。而传染性法氏囊病超强毒攻击子代雏鸡后 ,未免疫的子代雏鸡 ,外周血液和免疫器官组织的上述各项指标均明显低于疫苗免疫的子代雏鸡 ,这与 IBDV感染雏鸡后 ,其免疫器官组织严重损害 ,淋巴细胞变性坏死等有关 ,也是导致感染雏鸡免疫抑制的基础     

Protection from experimental asthma by an endogenous bronchodilator

Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.     

小鼠急性缺氧后淋巴结内肥大细胞的观察

应用组织化学染色法对对照组、缺氧组、牛磺酸预处理缺氧组小鼠淋巴结内肥大细胞的数量、活性、分布范围及组化性质进行研究.结果表明:随着急性缺氧时间的延长,缺氧组和牛磺酸预处理缺氧组小鼠的肥大细胞和脱颗粒数急剧增加,均极显著高于同期对照组(P<0.01),且在急性缺氧5h时肥大细胞出现一个峰值,而在缺氧8h后恢复常压9h再缺氧3h时,肥大细胞脱颗粒数最显著.AB-S染色显示:随着缺氧时间的延长,缺氧组和牛磺酸预处理缺氧组小鼠淋巴结内几乎全部为黏膜肥大细胞(mucosal mast cell MMC).     

Dot－ELISA在鸡IBD免疫检测及诊断中的应用研究

利用鸡传染性法氏囊病病毒（ＩＢＤＶ）细胞适应株在鸡胚ＣＥＦ单层培养物上增殖后经超速冷冻离心制备抗原，以国产ＮＣ膜为载体建立了检测与诊断鸡ＩＢＤ的Ｄｏｔ－ＥＬＩＳＡ方法。经与ＡＧＰ、ＶＮ、ＥＬＩＳＡ等方法进行比较，表明本方法灵敏，快速，简易，特异性强，重复性良好。对ＩＢＤ免疫抗体的检测结果表明，采用首次以ＩＢＤ弱毒苗与灭能油乳剂苗同时免疫、再次用油乳剂苗加强免疫的接种程序，可获得显著而持久的抗体水平；带母源抗体（ＭＡｂ）的雏鸡于２１日龄首次免疫，效果良好；带ＭＡｂ的鸡胚于１８日胚龄接种ＩＢＤ弱毒苗，雏鸡出壳后可在较长时间内获得良好的保护。     

急性缺氧对小鼠丘脑肥大细胞的影响

应用组织化学方法对对照组、缺氧组以及雌激素预处理缺氧组小鼠脑内肥大细胞(Mast Cell,MC)的数量、活性、分布范围及组化性质进行研究.结果表明:肥大细胞主要分布于小鼠丘脑,随急性缺氧时间的延长,缺氧组和雌激素预处理缺氧组小鼠丘脑内肥大细胞和脱颗粒数量急剧增多,均极显著高于同期对照组(P<0.01),且缺氧组在急性缺氧8 h和恢复正常9 h再缺氧3 h时,肥大细胞的脱颗粒现象最显著.而雌激素预处理缺氧组小鼠肥大细胞和脱颗粒数量均极显著低于同期缺氧组(P<0.01).AB-S染色显示,小鼠脑内绝大多数为黏膜肥大细胞,少数为结缔组织肥大细胞.研究结果表明:丘脑肥大细胞可能参与急性缺氧造成脑损伤的病理过程,雌激素作为肥大细胞膜的稳定剂对脑损伤起保护作用.     

特异性敲除肠道miR-146a对小鼠肠道菌群的影响

【目的】miR-146a作为抑炎因子,仍然不清楚其是否参与宿主与微生物间的互作,进而影响肠道稳态,因此本文旨在研究miR-146a对小鼠肠道菌群的影响。【方法】以肠道miR-146a特异性敲除小鼠(CKO鼠)及对照小鼠(Flox鼠)为研究对象,利用16S rRNA高通量测序法检测2组空肠段的微生物菌群分布。【结果】测序共获得1 134个用于物种分类的OTUs,包括37门、80纲、161目、198科、261属、117种的细菌;Flox组和CKO组小鼠的空肠微生物中共有46个相同的OTUs;各组肠道微生物中厚壁菌门Firmicutes、拟杆菌门Bacteroidota、疣微菌门Verrucomicrobiota、变形菌门Proteobacteria和脱硫杆菌门Desulfobacterota是优势菌门;2组肠道微生物群落组成整体相似,但CKO组梭状芽孢杆菌纲Clostridia的平均相对丰度高于Flox组(P=0.067),毛螺菌目Lachnospirales平均相对丰度显著高于Flox组(P<0.05),其他层级组成无显著差异。【结论】miR-146a敲除可改变宿主肠道梭状芽孢杆菌...     

鸡马立克氏病疫苗免疫后的免疫学变化

实验对１日龄雏鸡接种ＭＤ三价疫苗或ＨＶＴ疫苗后的免疫应答变化进行了检测．发现ＭＤ疫苗免疫后：（１）脾脏、胸腺Ｔ细胞ＩＬ—２诱生活性和ＩＬ—２Ｒ表达明显增强或增多，表明ＩＬ—２的免疫调节作用增强；（２）胸腺、法氏囊和脾脏中Ｔ细胞和抗体生成细胞数量及Ｔ细胞增殖功能明显增高，表明中枢与外周免疫器官的细胞免疫和体液免疫应答显著增强；（３）盲肠扁桃体、哈德尔腺、支气管粘膜淋巴组织中Ｔ细胞和抗体生成细胞数量以及泪液、气管液、肠液、胆汁中ＩｇＡ，ＩｇＧ，ＩｇＭ含量明显增多，表明呼吸道与消化道的局部免疫应答也显著增强；（４）ＭＤ三价疫苗免疫鸡的上述免疫应答变化比ＨＶＴ疫苗免疫鸡明显．     

兔圆小囊产溶菌酶细胞的免疫电镜组织化学观察

 采用免疫组织化学和免疫电镜细胞化学的方法 ,对兔圆小囊组织中产溶菌酶细胞进行了观察。免疫组织化学观察发现 ,产溶菌酶阳性细胞在兔圆小囊的粘膜上皮、圆顶上皮以及淋巴组织的滤泡生发中心、圆顶区和帽区均有分布 ,且受到多杀性巴氏杆菌感染后 ,阳性细胞增多 ,阳性反应增强。免疫电镜结果显示 ,在兔圆小囊的淋巴组织DNES细胞的颗粒中发现溶菌酶免疫组织化学阳性反应物。这一重要发现为神经 内分泌 免疫网络学说提供了新的证据。     

植物精油对尿素氮在瘤胃内容物中分布的影响

【目的】揭示尿素氮在奶牛瘤胃内容物中的分布特点,阐明精油对尿素氮分布和瘤胃发酵的影响。【方法】在含瘤胃液和15N尿素的发酵瓶中,加入终浓度为300 mg•L-1大蒜精油、茶树精油和尤加利精油,发酵后检测微生物中15N的丰度和瘤胃发酵指标,并利用DGGE刻画细菌群落变化。【结果】随着发酵时间的增加,瘤胃液中的尿素氮逐渐降低,而瘤胃固相和液相微生物中的尿素氮逐渐升高,发酵24 h 三者中的尿素氮基本持平。发酵24 h时,与空白对照组相比,大蒜精油处理组瘤胃固相和液相微生物尿素氮丰度分别降低了22.60%和18.75%,发酵液pH和氨氮浓度分别降低了3.02%和17.80%,异丁酸和乙酸/丙酸值有所升高。茶树精油和尤加利精油则显著降低了发酵液pH（P＜0.05）,提高了异丁酸和乙酸/丙酸值。DGGE图谱显示,发酵24 h时,3种植物精油可改变瘤胃细菌的群落结构。【结论】瘤胃尿素氮逐渐由瘤胃液向微生物中富集,大蒜精油可减缓尿素氮富集速度,改变细菌群落的组成,抑制氨氮生成。     

白头翁复方对腹泻小鼠肠道粘膜乳糖酶活性的影响

为了探讨白头翁复方对腹泻小鼠肠道粘膜乳糖酶活性的影响,取体重相近BALB/c小鼠180只,随机分预防组、治疗组、自愈组和对照组,每组45只,本试验采用Dahlqvist的方法测定各组小鼠前、中、后段肠道粘膜乳糖酶的活性。结果表明:预防组和治疗组乳糖酶的活性显著高于自愈组(P0.01),预防组和治疗组的差异不显著(P0.05)。说明白头翁复方能够显著增强腹泻小鼠肠道粘膜上乳糖酶的活性,表明白头翁复方治疗腹泻的作用机理可能与调节乳糖酶的活性有关。     

生活垃圾接种微生物堆肥对腐殖组分的影响

利用外源微生物(美商复合菌,MS;东农发酵菌,DN)进行城市生活垃圾堆肥。在堆肥过程中,系统地分析了腐殖酸组分的动态变化。结果表明,在生活垃圾堆肥过程中,腐殖质、胡敏酸含量在堆肥前期呈明显的降低趋势,但至堆肥腐熟期,又逐渐升高。堆肥结束后,外源微生物处理胡敏酸的含量明显高于不接种外源微生物处理。富里酸的含量在整个堆肥周期内呈较为明显的下降趋势,外源微生物处理富里酸的含量在堆肥的不同时期均低于不接种外源微生物处理。在城市生活垃圾堆肥过程中,腐殖化指数(HI)、胡敏酸的百分含量(HP)在堆肥周期内则呈明显的上升趋势,表明在堆肥过程中腐殖酸的腐殖化程度增加。在堆肥后期,外源微生物处理HI,HP值明显高于不接种外源微生物处理,其中DN处理效果强于MS复合菌处理。     

Immune Responses of Chicken Immunized with Marek‘s Disease Vaccines

The experiment was conducted to study the dynamic changes of immune responses of chicks immunized with Marck‘s disease(MD) trivalent vaccine and turkey herpesvirus (HVT)at one day age.Results were found that after immunization of chicks with MD vaccines,the interlcukine-2 (IL-2) inductive activity and IL-2 receptor expression of T cells from thymus and spleen significantly increased.suggesting that the immunoregulative function was markedly enhanced in the immune organs;the number of antibody-producing cells,the number and proliferative function of T cells rose markedly in Bursa Fabricius,Splcen and thymus,indicating that the ccllular and humoral immune responses were elevated remarkablly in the central and peripheral immune organs; the number of T and antibody-producing cells as well as the content of IgG,IgA and IgM obviously mounted in cecal tonsil,Harder ian gland mucosal lymphoid tissucs of bronchus along with tears,trachea washings,bilc and intestinal fluids,demonstrating that the local and mucosal immunity was raised in the respiratory and digestive tract;the levels of immune responses mentioned above in the trivalent vaccine-immuniacd chicks were apparently higher than those of HVT-immunized birds.     

Treatment of murine colitis by Lactococcus lactis secreting interleukin-10

The cytokine interleukin-10 (IL-10) has shown promise in clinical trials for treatment of inflammatory bowel disease (IBD). Using two mouse models, we show that the therapeutic dose of IL-10 can be reduced by localized delivery of a bacterium genetically engineered to secrete the cytokine. Intragastric administration of IL-10-secreting Lactococcus lactis caused a 50% reduction in colitis in mice treated with dextran sulfate sodium and prevented the onset of colitis in IL-10(-/-) mice. This approach may lead to better methods for cost-effective and long-term management of IBD in humans.