Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A.

BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs)) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs. 1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD.     

An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

急性重症胆管炎大鼠病理生理学变化的实验研究

目的 :探讨急性重症胆管炎 (ACST)的病理生理学变化。方法 :制造急性重症胆管炎模型。实验大鼠随机分为正常组和ACST组。分别采用偶氮显色法和产色基质法测定外周血总胆红素和内毒素浓度。应用MTT法检测TNF、IL - 1、IL - 2和IL - 6活性。使用电子自旋共振仪和酸滴定法测定血氧自由基及血清磷脂酶A2 含量。通过放免分析方法检测PGFα/TXB2 比值。采用间接免疫荧光法观察T -淋巴细胞亚群。应用多功能生化测定仪检测补体和免疫球蛋白。结果 :急性重症胆管炎大鼠外周血总胆红素和内毒素浓度较正常组明显升高(p<0 0 0 1,p <0 0 5 ) ;TNF、IL - 1、IL - 2和IL - 6水平明显高于正常组 (p <0 0 5 ,p <0 0 1) ;血氧自由基、血清磷脂酶A2 含量明显升高 (p<0 0 1,p <0 0 5 ) ,PGFα/TXB2 ,比值明显降低 (p <0 0 5 )。急性重症胆管炎大鼠CD3 百分率明显高于正常组 (p <0 0 1) ,CD4/CD8比值明显低于正常组 (p <0 0 1) ;补体C3 和C4,免疫球蛋白LgM和IgA均明显高于正常组 (p <0 0 5 ,p<0 0 1)。结论 :急性重症胆管炎大鼠处在过度炎症反应、免疫功能紊乱状态 ,因此阻断细胞因子等炎症介质所致的继发性细胞损伤是其至关重要的治疗环节。     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Innate Immunity and Organ Transplantation: The Potential Role of Toll-like Receptors

Traditionally, the recognition and tolerance of transplanted grafts has been considered to be within the realm of the adaptive immune system. Innate immunity, on the other hand, as the first line of host defense, plays a role in fighting against invading microorganisms. Recently, with the discovery of the Toll-like receptors (TLRs), the role of innate immune responses in the control of adaptive immunity has become a new area of interest. Emerging evidence suggests that in addition to responding to pathogen-associated molecular patterns of microorganisms, TLRs can be activated by endogenous ligands, expressed by mammalian cells. These 'danger signals' may participate in ischemia-reperfusion related organ damage and subsequently influence function and survival of transplanted grafts. Furthermore, it has been suggested that adaptive immune responses can enhance the acute inflammatory responses controlled by innate immunity in organ transplantation. This review addresses the potential involvement of TLRs in different stages of organ transplantation. Intriguing and controversial findings are presented and discussed in order to stimulate more attention to this emerging and potentially important area of research in organ transplantation.     

人参根总皂甙对效应激小鼠免疫功能的影响

小鼠在45℃高温环境下暴露15min,其网状内皮系统对碳粒的廓清作用明显降低,血清溶血素含量显著下降,绵羊红细胞(SRBC)诱发的迟发型超敏反应明显受到抑制.应激前15min人参根总皂甙(GRS)50、100 mg·kg~(-1),ip,对小鼠的免疫功能有保护作用,可使热应激小鼠网状内皮系统对碳粒的廓清作用免于下降,防止血清溶血素含量的降低,迟发超敏反应不受抑制.     

分娩方式对新生儿补体系统,体液免疫水平的影响

为研究分娩方式是否影响新生儿免疫状态，检测和比较了６８例妊娠足月阴道产和６４例妊娠足月部宫产分娩的新生儿脐血Ｃ３、Ｃ４及ＩｇＧ、ＩｇＡ、ＩｇＭ的含量，其结果：ＩｇＧ的的含量阴产组明显高于剖宫产组，且男婴阴道产组ＩｇＧ的信明显高于剖宫产。说明剖宫产可参降低新生儿免疫应签及抗感染能力。     

粉被虫草提取物对巨噬细胞吞噬功能及CTL活性的影响

研究粉被虫草菌丝体提取物在体外对小鼠腹腔巨噬细胞吞噬功能和脾细胞免疫功能的影响，结果表明：粉被虫草提取物在正常情况下不仅能够促进小鼠腹腔巨噬细胞的吞噬功能，而在免疫抑制的情况下，一定浓度的粉被虫草菌丝体提取物还能恢复提高吞噬功能；它不仅能促进正常脾活化Ｔ细胞的增殖，而且能恢复环磷酰胺和氢化可的松抑制免疫小鼠脾活化Ｔ细胞的增殖；在较高浓度下能增高小鼠脾细胞毒Ｔ淋巴细胞（ＣＴＬ）活性，同时在一定浓度下能恢复免疫抑制小鼠脾ＣＴＬ活性。     

Protective immunity to malaria: studies with cloned lines of rodent malaria in CBA/Ca mice. IV. The specificity of mechanisms resulting in crisis and resolution of the primary acute phase parasitaemia of. Plasmodium chabaudi chabaudi and P. yoelii yoelii

Low numbers of parasites from cloned lines of the rodent malaria parasites, Plasmodium chabaudi chabaudi AS and P. yoelii yoelii A, injected into CBA/Ca mice produce acute but usually self-limiting infections. During crisis, i.e. 1-2 days after peak parasitaemia, 'pre-immune' mice experiencing such 'background' infections were reinfected intravenously with homologous parasites or parasites of heterologous strains or species. P. c. chabaudi AS pre-immune mice controlled an AS challenge with essentially the same kinetics as the background infection. Reinfection of AS pre-immune mice with the heterologous (CB and IP-PCI) P. c. chabaudi strains or P. chabaudi adami DS had little effect on the initial growth of these parasites, although eventually the parasitaemia was controlled. In contrast, a partial inhibitory effect on the growth of P. vinckei lentum DS was evident. Challenge with the non-lethal (A) or lethal (YM) variants of P. y. yoelii resulted in an increase in both the growth and virulence of these parasites. P. y. yoelii A pre-immune mice controlled a homologous challenge, but were less effective at controlling the YM variant. In addition, they were unable to clear rapidly a P. c. chabaudi AS or P. v. lentum DS challenge. Both the multiplication and virulence of P. berghei ANKA were enhanced. These findings demonstrate that resolution of the primary acute parasitaemia in P. c. chabaudi AS- and P. y. yoelii A-infected mice is predominantly mediated by species- and strain-specific mechanisms.     

益气补肾汤对小鼠免疫功能的影响

目的 :研究益气补肾汤对小鼠免疫功能的影响。方法 :用药理实验的方法 ,将小鼠制成免疫抑制模型 ,灌服益气补肾汤 ,观察和测定小鼠巨噬细胞吞噬功能 ,胸腺、脾指数 ,迟发性超敏反应及溶血素抗体水平。结果 :灌服益气补肾汤的小鼠与灌服蒸馏水的免疫抑制模型小鼠相比 ,巨噬细胞吞噬能力增强 (P <0 .0 5 ) ,胸腺指数升高(P <0 .0 5 ) ,迟发性超敏反应增强 (P <0 .0 5 ) ,且血清溶血素抗体升高 ,脾指数 2组间差异无统计学意义。结论 :益气补肾汤可增强机体免疫功能