不同免疫状态肺隐球菌病临床特点分析

目的总结国内不同免疫状态人群肺隐球菌病（Pulmonary cryptococcosis,PC）临床特点,以提高该病的临床诊治水平。方法回顾性分析1998～2009年上海多家教学医院的100例Pc患者临床资料。结果既往无基础疾病史者占46．00％。临床以咳嗽、咳痰、发热为主要首发症状。无症状者多见于非免疫受损患者。非免疫受损PC病灶以胸膜下分布为主（55．22％）,单肺累及占72．97％,病灶位于肺野局部者占59．46％,病灶形态以结节／肿块影为主（55．41％）;而免疫受损患者病灶表现多样化,分布广泛而随机。19例患者行经支气管镜肺活检（TBLB）,病理结果阳性14例（73．68％）。36例患者行经皮肺穿刺活检（PCNB）,病理阳性26例（72．22％）。结论既往无基础疾病不能排除Pc可能。非免疫受损Pc患者病灶多靠近胸膜,病变较局限,形态以结节／肿块影多见。免疫受损患者病灶表现多样化,分布广泛而随机。TBLB和PCNB诊断PC阳性率较高,且两者可互为补充。     

植物防御反应与动物免疫应答的比较及其对应性初探

动物经过数亿年的进化直到脊椎动物阶段出现了渐为完整的免疫系统。植物在与各种病原的共进化过程中亦发展了自身的防御系统。随着对植物抗病性的概念及植物防御机制的不断认识,人们发现它与动物的免疫应答有着众多的对应性。这些对应性是否表明植物的防御系统与动物的免疫系统在进化上具有同一性,是否表明它们在防御反应上具有类似的机制值得深思 。     

Sexual dimorphism in immune response: Testing the hypothesis in an insect species with two male morphs

It has been proposed that given that males should invest in sexual traits at the expense of their investment in immune response, females are better immunocompetent than males. Typically, this idea has been tested in monomorphic species, but rarely has been evaluated in polymorphic male species. We used Paraphlebia zoe, a damselfly with two male morphs: the black‐winged morph (Black‐W) develop black spots as sexual traits and the hyaline‐winged morph (Hyaline‐W) resembles a female in size and wings color. We predicted that Black‐W should have a lower immune response than Hyaline‐W, but that the latter males should not differ from females in this respect. Nitric oxide (NO) and phenoloxidase (PO) production, as well as hemolymph protein content, were used as immune markers. Body size (wing length) was used as an indicator of the male condition. The results show that, as we predicted, females and Hyaline‐W had higher values of NO than Black‐W, corresponding to differences in size. However, the opposite was found in relation to PO production. Females had the highest levels of hemolymph protein content, whereas no differences were found between Black‐W and Hyaline‐W. These results partially support the sexual selection hypothesis and are discussed in the context of the life history of this species. Black‐W, Hyaline‐W, and females could express the immune markers that are prioritized by their particular condition, and probably neither of them could express all immune markers in an elevated manner, as this would result in an excessive accumulation of free radicals.     

Decreased immune response as a proximate cost of copulation and oviposition in a damselfly

Abstract.Males and females of the Japanese calopterygid damselfly, Matrona basilaris japonica Fester, showed a rapid (within 24 h), and significant reduction in immune system function (encapsulation response) after reproductive activity (copulation or oviposition).
 A similar, but non‐significant, change occurred in males that conducted energetically costly behaviour (fighting).
 These data suggest that there may be physiological costs other than energy‐based trade‐offs associated with copulation and oviposition that may have life‐history consequences via their effects on immune system function.     

七鳃鳗鳃黏膜免疫系统类淋巴细胞免疫应答遗传基础

近年来,在无颌类脊椎动物七鳃鳗体内发现了以可变淋巴细胞受体(Variable lymphocyte receptors, VLR)为基础的抗原识别机制。为揭示七鳃鳗鳃黏膜免疫系统中类淋巴细胞适应性免疫应答的遗传基础,探索无颌类与有颌类脊椎动物在适应性免疫应答机制上的进化关系,本文构建了日本七鳃鳗(Lampetra japonica)鳃囊组织免疫前后cDNA文库并进行了高通量转录组测序及分析。通过对组装得到的88 525个独立基因(Unigene)进行功能注释,分别有21 704和9769个unigene在GO(Gene Ontology)和KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库得到注释。999个unigene参与免疫系统的多个通路,其中184个与高等脊椎动物TCR(T cell receptor)和BCR(B cell receptor)信号通路的51个分子具有较高的同源关系,说明七鳃鳗体内存在高等脊椎动物适应性免疫应答信号通路的相关分子。本文还发现5个VLRA、7个VLRB和4个VLRC分子,说明七鳃鳗鳃黏膜免疫组织内至少分布3种类淋巴细胞亚群。实时荧光定量PCR结果显示,Lck、Fyn和Zap70基因在免疫激发后表达量显著上调,而Syk、Btk和Blnk基因表达没有显著变化,说明七鳃鳗鳃组织受到抗原刺激后,类似T淋巴细胞的信号转导途径被激活。本研究初步证明,尽管无颌类和有颌类脊椎动物的适应性免疫系统在抗原识别机制上存在不同,但具有共同的遗传基础。研究结果为探讨七鳃鳗VLRA⁺、VLRB⁺和VLRC⁺淋巴细胞免疫应答信号传导过程提供了有价值的线索。     

Current status of immune mechanisms of killing of intracellular microorganisms

The interaction between intracellular pathogens and the mammalian host follows different pathways that reflect evolved survival mechanisms of both the pathogen and the host to assure each one's own survival. From the host's perspective, different immune mechanisms predominate at different stages of infection. Both phagocytic and non-phagocytic target cells participate in microbial uptake and, in some cases, intracellular destruction. In addition, the development of specific immunity ensures sustained activation of intracellular microbicidal mechanisms in the target cells, and induction of apoptotic or lytic target cell death by cytotoxic T lymphocytes. From the pathogen's perspective, different evasion strategies are employed to counteract host defenses. Understanding microbial survival strategies and the immune mechanisms that result in killing of intracellular pathogens will deepen our insight into the pathogenesis of infection that could be applied towards the development of effective vaccination and immunotherapy.     

肠道菌群参与宿主免疫应答的作用及机制研究进展

肠道菌群作为动物体内重要的组成部分,能够直接参与机体的免疫调控作用,促进机体免疫系统发育,维持正常免疫功能。同时,免疫系统对肠道菌群又有调控和制约作用。本文主要综述了肠道菌群的组成以及影响肠道菌群变化的因素,系统阐述了肠道菌群与疾病相互作用的机制,总结了肠道菌群在宿主感染与免疫应答中的作用,为开展肠道菌群参与机体免疫应答的机制方面的研究提供新的思路。     

Humoral immune response against soluble and fractionate antigens in experimental sporotrichosis

Sporotrichosis is a chronic granulomatous mycosis caused by the dimorphic fungus Sporothrix schenckii, which is widely distributed in nature, and presents a saprophytic mycelial form on plant debris and soil. The immunological mechanisms involved in the prevention and control of sporotrichosis are not yet fully understood. In this study, mice were studied after infection with Sporothrix schenckii. In the first week after infection, fungal loading increased and thence decreased drastically 14 days after infection. Analysis by immunoblotting showed that the sera of all mice tested had antibodies reacting only with a 70 kDa antigen, with predominance of IgG1 and IgG3. Taken together, our results show that antigens from S. schenckii induced a specific humoral response in infected mice.     

Modulation of the immune response by Middle East respiratory syndrome coronavirus

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.     

MITA/STING: A central and multifaceted mediator in innate immune response

The recognition of nucleic acids is a general strategy used by the host to detect invading pathogens. Many studies have established that MITA/STING is a central component in the innate immune response to cytosolic DNA and RNA derived from pathogens. MITA can act both as a direct sensor of cyclic dinucleotides (CDNs) and as an adaptor for the recruitment of downstream signaling components. In both roles, MITA is part of signaling cascades that orchestrate innate immune defenses against various pathogens, including viruses, bacteria and parasites. Here, we highlight recent studies that have uncovered the molecular mechanisms of MITA-mediated signal transduction and regulation, and discuss some notable issues that remain elusive.     

The study of cell-mediated immune response in recurrent vulvovaginal candidiasis

The aim of this work was to examine in vitro the ability of cells from patients with recurrent vulvovaginal candidiasis (RVVC) to cell-mediated immune response. Peripheral blood mononuclear cells (PBMC) and whole blood cells (WBC) of 37 RVVC patients in acute infection and 14 in remission were examined for the ability to proliferation and cytokines production (IFN, TNF, IL-6). As a control, a group of 25 healthy women were examined. The cells were stimulated with Candida antigen (HKCA), LPS and PHA. To indicate the level of cytokines, the following cell-lines were used: A549 for IFN, WEHI 164 for TNF and 7TD1 for IL-6. The proliferation/death of cells was determined by colorimetric test using MTT. Distinct suppression of cell-mediated immune response (CMI) was shown in all patients comparing to the control. Greatest suppression was found in the acute phase of the disease. The ability of cells to proliferate and produce IFN increases only in remission. The data seem to suggest that in this phase of disease, the ability of cell-mediated immune response is restored. It was also indicated that IFN may take part in protection against Candida infection.     

Dietary supplementation with a nucleotide-rich yeast extract modulates gut immune response and microflora in weaned pigs in response to a sanitary challenge

An experiment was carried out to evaluate the short-term effect of supplementing a nucleotide-rich yeast extract (NRYE) on growth performance, gut structure, immunity and microflora of piglets raised under sanitary and unsanitary conditions. A total of 84, 21-day old piglets were used in this study; 42 piglets were raised in a room designated as the clean room that was washed once per week, whereas the other 42 piglets were raised in a room designated as the unclean room in which 7 kg of manure from the sow herd was spread on each pen floor on day 1 and 7 and the room was not washed throughout the experiment. The pigs were fed a corn–soybean meal-based diet without or with 0.1% NRYE. Each treatment had 7 replicate pens in each room, and each pen housed 3 pigs. Feed disappearance and BW were recorded on day 1 and 14. On day 14, one pig per pen was euthanized to collect ileum, mesenteric lymph nodes and spleen tissues, and cecum and colon digesta. Overall, NRYE supplementation did not affect growth performance in both clean and unclean conditions, improved kidney weight in both clean (P=0.0002) and unclean room (P<0.0001) and tended to improve the villus height/crypt depth ratio in the clean room (P=0.073). Supplementing NRYE was associated with upregulation of Ileal programmed cell death gene-1 (P=0.0003), interleukin (IL)-1β (P<0.0001), IL-6 (P=0.0003), IL-10 (P<0.0001) and tumor necrosis factor-α (TNF-α) (P<0.0001) in pigs raised in the unclean room. Supplementing the NRYE in pigs raised in the clean room suppressed growth of cecal Enterobacteriacea (P<0.0001) members and colonic Enterococcus spp. (P<0.019), improved proliferation of cecal Lactobacillus spp. (P<0.002) and colonic Clostridium cluster IV (P<0.011) and XVIa members (P<0.0002). Supplementing the NRYE in the unclean room improved proliferation of cecal Clostridium cluster IV (P<0.026) and suppressed proliferation of colonic Enterococcus spp. (P<0.037). In conclusion, supplementing the NRYE to piglets under unsanitary conditions improved ileal immune response by upregulating inflammatory cytokines, and positively modulated proliferation of beneficial gut bacteria and suppression of harmful ones in both clean and unclean rooms.     

结核免疫应答相关白细胞介素的作用机制研究进展

白细胞介素(简称白介素)能够调控免疫细胞的分化、增殖及效应功能。结核抗原特异性诱导的白介素的表达水平能够表征结核杆菌感染后的机体状态。在机体的抗结核免疫应答中,白介素可以直接调控吞噬细胞对胞内感染结核杆菌的杀菌活性;也能够调控效应性T细胞的增殖,并进一步激活吞噬细胞的杀菌功能。目前,部分白介素已被证明有望用于结核病的免疫辅助治疗,正在进行相关临床实验。本文对白介素调控免疫细胞抗结核免疫应答的研究进展进行综述,以期为制定结核病的白介素免疫辅助治疗方案提供指导。     

Humoral immune response in lactating dairy cows after repeated exposure to human chorionic gonadotropin

Our objective was to determine if repeated exposure of lactating dairy cows to human chorionic gonadotropin (hCG) would induce an antibody (Ab) response against hCG. Cows either received an hCG injection (hCG; n = 24, each given 2000 IU im) or no treatment (CON; n = 22) 18 days after a timed AI (TAI) and 7 days before initiation of Ovsynch for resynchronization of ovulation and TAI. A subgroup of cows continued in the experiment to receive a second hCG injection (n = 17) 35 days after the first exposure to hCG, whereas another subgroup served as controls (n = 9). Another subgroup of cows continued in the experiment to receive a third hCG injection (n = 11) 35 days after the second exposure to hCG, whereas cows not receiving hCG served as controls (n = 8). A binding radioimmunoassay was used to detect hCG antibodies in serum samples collected 0, 7, 14, 21, and 28 days after treatment. A positive Ab response (>6.2% bound) was defined as three standard deviations above CON binding. No cows had hCG antibodies at Day 0 before the first exposure to hCG. After the first hCG treatment, there was no difference (P = 0.52) between Ab positive cows in CON (0%) and hCG (4%) treatments. At the second hCG treatment, on Day 0 there was no difference (P = 0.65) between CON (0%) and hCG (6%) cows, whereas, more (P = 0.02) hCG cows (47%) were positive than CON cows (0%) within 28 days of the hCG injection. At the third hCG injection, hCG cows tended (P = 0.09) to have a greater percentage of Ab positive (36%) than CON cows (0%), whereas after the injection, a greater (P < 0.01) percentage of hCG cows were positive (hCG = 73% vs. CON = 0%). After the second and third exposure to hCG, 8 of 17 and 8 of 11 cows within the hCG group had greater percent Ab bound at 7, 14, 21, and 28 days after hCG than cows in CON and those with no Ab response. The greatest percent Ab binding occurred at 14 days after the second and third hCG exposure. We concluded that some but not all lactating dairy cows developed an Ab response after repeated exposure to hCG and that maximum response occurred within 14 days after hCG exposure.     

An Mhc class I allele associated to the expression of T-dependent immune response in the house sparrow

The major histocompatibility complex (Mhc) encodes for highly variable molecules, responsible for foreign antigen recognition and subsequent activation of immune responses in hosts. Mhc polymorphism should hence be related to pathogen resistance and immune activity, with individuals that carry either a higher diversity of Mhc alleles or one specific Mhc allele exhibiting a stronger immune response to a given antigen. Links between Mhc alleles and immune activity have never been explored in natural populations of vertebrates. To fill this gap, we challenged house sparrows (Passer domesticus) with two T-dependent antigens (phytohemagglutinin and sheep red blood cells) and examined both primary and secondary immune responses in relation to their Mhc class I genotypes. The total number of Mhc alleles had no influence on either primary or secondary response to the two antigens. One particular Mhc allele, however, was associated with an increased response to both antigens. Our results point toward a contribution of the Mhc, or of other genes in linkage disequilibrium with the Mhc, in the regulation of immune responses in a wild animal species.     

A monte carlo approach to population dynamics of cells in a HIV immune response model

Summary Using a direct Monte Carlo simulation, population growth of helper T-cells (N _H) and viral cells (N _v) is studied for an immune response model with an enhanced spatial inter-cellular interaction relevant to HIV as a function of viral mutation. In the absence of cellular mobility (P _mob=0), the helper T-cells grow nonmonotonically before reaching saturation and the viral population grows monotonically before reaching a constant equilibrium. Cellular mobility (P _mob=1) enhances the viral growth and reduces the stimulative T-cell growth. Below a mutation threshold (P _c), the steady-state density of helper T-cell (p _H) is larger than that of the Virus (p _v); the density difference Δp _o(=pV−pH) remains a constant at P _mob=1 while −Δp _o→0 as P _mut→P _c at P _mob=0. Above the mutation threshold, the difference Δp _o in cell density, grows with ΔP=P _mut−P _c monotonically: ΔP _o ∞ (ΔP)^β ≃ with β≈0.574±0.016 in absence of mobility, while Δp _o≈6(ΔP) with P _mob=1.     

Overexpression of oncostatin M receptor regulates local immune response in glioblastoma

Glioblastoma (GBM) is the most lethal cancer in central nervous system. It is urgently needed to look for novel therapeutics for GBM. Oncostatin M receptor (OSMR) is a cytokine receptor gene of IL-6 family and has been reported to be involved in regulating GBM tumorigenesis. However, the role of OSMR regulating the disrupted immune response in GBM need to be further investigated. Three gene expression profiles, Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) data set (GSE16011), were enrolled in our study and used for OSMR expression and survival analysis. The expression of OSMR was further verified with immunohistochemistry and western blot analysis in glioma tissues. Microenvironment cell populations-counter (MCP-counter) was applied for analyzing the relationship between OSMR expression and nontumor cells. The functions of OSMR in GBM was investigated by Gene Ontology, Gene set enrichment analysis (GSEA), gene set variation analysis and so on. The analysis of cytokine receptor activity-related genes in glioma identifies OSMR as a gene with an independent predictive factor for progressive malignancy in GBM. Furthermore, OSMR expression is a prognostic marker in the response prediction to radiotherapy and chemotherapy. OSMR contributes to the regulation of local immune response and extracellular matrix process in GBM. Our findings define an important role of OSMR in the regulation of local immune response in GBM, which may suggest OSMR as a possible biomarker in developing new therapeutic immune strategies in GBM.