随机病原体-免疫模型的持久性与灭绝性

研究了带有环境白噪声的随机病原体-免疫模型,应用伊藤公式和Lyapunov函数,推导出随机模型全局唯一正解的存在性、病原体灭绝和均值强持久的充分条件.并利用数值模拟验证了理论结论.最后,讨论了在病原体与免疫细胞相互作用过程中,体内微环境噪声对病原体生存状态的影响.

具扩散性的病原体-宿主免疫模型的Turing不稳性

为了研究在病原体与宿主免疫细胞相互作用过程中存在的扩散因素对其动力学的影响,建立了带有齐次Neumann边界条件的病原体-宿主免疫反应扩散模型。以病原体与免疫细胞的扩散比率ρ为参数,利用偏微分方程理论,讨论了在正平衡解处线性化系统特征根的分布,得到模型在正平衡解处经历Turing不稳性的临界条件。并利用Matlab数值模拟了病原体-宿主免疫模型经历Turing不稳性的动力学现象,进一步讨论了Turing不稳性的动力学现象所蕴含的病原体与免疫细胞的扩散机理。

Immunogenicity of the Spike Glycoprotein of Bat SARS-like Coronavirus

A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.

Antiviral effect of polysaccharide from Spirulina platensis(PSP) on HSV-2 in vitro

To explore the antiviral effect and mechanism of polysaccharide from Spirulina platensis （PSP） on herpes simplex virus type 2 （HSV-2）, a standard strain of HSV-2 （333 strain） was used to investigate the antiviral effect of PSP in vitro. PSP in various concentrations was applied to different stages of HSV-2 replication cycle. Finally, the virus infectivity （TCID50）, cytopathic effect （CPE）, and MTT staining method for viable cells （MTT assay） were used as markers to evaluate the effect of PSP on HSV-2. The quantity of HSV-DNA was detected by real-time fluorescence quantitative PCR （FQ-PCR）. The HSV-2 infected Vero cell tdtrastructures were observed by transmission electron microscopy （TEM）. The results showed that PSP had little cytotoxic effect on Vero cells, it could not directly inactivate HSV-2 infectivity. PSP not only interfered in adsorption of HSV-2 to Vero cells but also inhibited HSV-2 biosynthesis in the ceils. FQ-PCR results showed that the inhibitory rate on HSV- DNA also increased in a dose-dependent and time-dependent manner. TEM also confirmed that PSP exhibited pronounced inhibitory effect on HSV-2. In conclusion, the antiviral effect of PSP on HSV-2 may be attributed to the inhibition of virus adsorption, virus replication and synthesis in cells.

Enemy at the gates： dendritic cells and immunity to mucosal pathogens

Dendritic cells （DC） are diverse and specialized hematopoietic cells serving as an essential bridge between innate and adaptive immunity. DC exist in all lymphoid and nonlymphoid organs and are amongst the first responders to infection at epithelial surfaces including mucosal tissues. DC of the lung, gut, and vaginal mucosa display different phenotypes and functions reflecting each unique tissue and, in contrast to their counterparts in spleen and lymph nodes, are constantly exposed to both harmful and benign factors of their environments. Mucosal DC recognize and respond to pathogens through engagement of pattern recognition receptors, and activated DC migrate to draining lymph nodes to induce adaptive immune responses. The specialized function of DC aids in the induction of immunity and pathogen control at the mucosa. Such specialization includes the potent antiviral interferon response of plasma- cytoid DC to viral nucleic acids, the ability of mucosal DC to capture organisms in the gut lumen, the capacity of DC to cross-present antigen from other infected cells, and the ability of mucosal DC to initiate lgA class switching in B cells. DC plasticity is also critical in the immune response to mucosal pathogens, as DC can respond to the microen- vironment and sense pathogen-induced stress in neighboring epithelial cells. Finally, DC interact with each other through crosstalk to promote antigen presentation and T-cell immunity. Together, these processes condition mucosal DC for the induction of a tailored immune response to pathogens.

What caused the increase of autoimmune and allergic diseases:A decreased or an increased exposure to luminal microbial components?

The dramatic increase of allergic and autoimmune diseases such as asthma, atopic dermatitis （eczema）, allergic rhinitis, inflammatory bowel disease （IBD, including both Crohn＇s disease and ulcerative colitis）, multiple sclerosis, and insulin-dependent diabetes mellitus （type Ⅰ diabetes） in the developed countries in the last century is a big puzle. ＂Hygiene Hypothesis＂ was proposed more than two decades ago and it suggested that the increase in these allergic and autoimmune diseases is caused by the aberrant development and response of the immune system due to a reduced exposure to microorganisms along with the improved hygiene. Interestingly, recent studies revealed that these allergic and autoimmune diseases are closely related to the microbes in the gut. For instance, even asthma, an allergic reaction of the lung to inhaled antigens, is closely related to a reduced exposure to foodborne and orofaecal microbes, rather than the amount of allergens in the air or the exposure to airborne microbes. It is known that bacteria in the gut could be 10 times in number of the eukaryotic cells of the body. Therefore, it would be not too surprising that microbes in the gut may have a great impact on these autoimmune and allergic diseases.

Characterization and application of monoclonal antibodies against Shewanella marisflavi, a novel pathogen of Apostichopus japonicus

Shewanella marisflavi strain AP629 was certified as a novel pathogen of the sea cucumber Apostichopusjaponicus. In this study, four monoclonal antibodies （MAbs） （3C1, 3D9, 2F2, 2A8） against strain AP629 were developed by immunizing Balb/C mice. 3C1 and 3D9 recognized S. marisflavi only, showing no cross reactivity to other gram-negative bacteria, However, 2F2 and 2A8 showed cross reactivity to all tested bacteria. Indirect immunofluorescence, and immunogold electron microscopy, showed the binding antigens of 3C1 and 3D9 were located at the secretion on the surface of strain AP629. The binding antigens of 2F2 and 2A8 were noted on the membrane of the cells. MAbs 3C1 and 3D9 recognized the lipopolysaccharide fraction of strain AP629, and 2F2 and 2A8 recognized in western-blotting protein antigens with molecular weights of 113 and 128 kDa respectively. MAbs 3C1 and 3D9 have the potential for use in pathogen diagnosis, epidemiology and studies on the mechanism of how S. marisflavi infects A. japonicus. Imrnunohistochemistry with 3C1 or 3D9 identified strain AP629 in the body wall of infected A. japonicus. In the adult sea cucumbers that were infected via body wall injection, positive signals were observed at the site of skin ulceration, and at the connective tissue of the non-ulcerated body wall. In addition, some large blue-stained cells aggregated at the connective tissue colonized by large numbers of bacteria. In juveniles infected via immersion infection, positive signals were observed at the cuticle of the body wall only. Our results suggest that 3C1 and 3D9 could be used in various immunological assays to study the invasion mechanism of strain AP629 in A. japonicus, the law of bacterial colonization, proliferation in different tissues of A. japonicus, and correlation between secretion on the surface of strain AP629 and its pathogenesis to A. japonicus.

Caspase Work Model During Pathogen Infection

Caspases are an evolutionarily conserved family of aspartate-specific cystein-dependent proteases with essential functions in apoptosis and normally exist in cells as inactive proenzymes. In addition to the inflammatory caspases, the initiator and effector caspases have been shown to have an important role in regulating the immune response, but are involved in different ways. We give a brief introduction on the benefit of apoptosis on the clearance of invasive pathogens, and the caspase functions involved in the immune response. Then we construct a working model of caspases during pathogen invasion. A detailed description of the three modes is given in the discussion. These three modes are regulated by different inhibitors, and there may be a novel way to treat intracellular pathogen and autoimmune diseases based on the specific inhibitors.

Tyrosinase,a new innate humoral immune parameter in large yellow croaker(Pseudosciaena crocea R)

We evaluated the immune response to infection with a pathogen in large yellow croaker(Pseudosciaena crocea Richardson).The fish were given an intraperitoneal(i.p.) injection of Vibrio parahaemolyticus or sterile sea water(control).We collected blood sera from the fish 0.17,1,2,4,8,12,or 16 d after injection(dpi).We measured tyrosinase activity and the concentrations of lysozyme,NOS,and antibodies.Serum tyrosinase activity was significantly higher at 0.17 and 4 dpi than in the control group,and peaked at 8 dpi.Lysozyme activity was significantly higher at 2 and 12 dpi than in the control group,but lower at 16 dpi.There is no statistical difference in the level of nitric oxides synthase(NOS) activity or antibodies between the control and injection groups.This is the first report of the tyrosinase activity in the serum of large yellow croaker.Our results indicate that tyrosinase plays an important role in the immediate immune defense against V.parahaemolyticus in large yellow croaker.Tyrosinase is a candidate parameter for investigation of fish innate immune defense.

Expression of Hantaan virus 26 kD fragment of nucleocapsid protein in insect cells and prelimimary study on its immunogenicity

Objective: To express the 26 kD fragment of Hantaan virus nucleocapsid protein that contains the major antigenic epitopes in insect cells, and make a preliminary analysis of its immunological characteristics. Methods: The recombinant baculovirus bac-S0.7 with the 700 bp fragment of S gene 5' terminal of Hantaan virus was constructed, and the antigenicity of the expression product was tested. Mice were injected with Sf9 cells infected by the recombinant baculovirus. The humoral and cellular immunological effects were identified by indirect immunofluorescence assay, micro-cell culture neutralization test and T lymphocytes stimulation test. Results: Immunized by bac-S0.7 infecting insect cells, specific antibody with the highest titer of 1∶1 600 was observed. The stimulation indexes of splenocytes of immunized mice to nucleocapsid protein of Hantaan virus was higher than the negative control. Conclusion: The expression product of S0.7 gene fragment in insect cells is immunogenic.

Relationship between Chlamydia pneumoniae infection and occurrence of bronchial asthma

Objective: To study the relationship between Chlamydia pneumoniae (C. pneumoniae) infection and asthma exacerbation. Methods: A prospective study of C. pneumoniae infection was conducted in 75 patients with asthma and 63 patients with respiratory tract infection, and 100 blood donors served as controls. The presence of infection was convinced by the polymerase chain reaction and direct immunofluorescence assay for C. pneumoniae DNA from throat swab specimens and micro-immunofluorescence testing for C. pneu-moniae-specific IgG, IgM and IgA antibodies. Results: Prevalence of specific IgG in asthma patients (81. 3%) was higher than that of the blood donors (68. 0%, P<0. 05) and was not significantly different from respiratory tract infection patients (68. 0%, P>0. 05). The acute C. pneumoniae infection rate of symptomatic asthma patients (59. 4%) was markedly higher than that of respiratory tract infection patients (34. 9% , P<0. 05). The average titer of C. pneumoniae IgG instead of IgA in asthma patients (48. 38±6. 94) was significantly higher than respiratory tract infection patients (24. 70±8. 77, P<0. 05). Other pathogens were identified in 12 of 21 (57. 1%) asthma patients with C. pneumoniae. The symptoms of 7 asthma patients with C. pneumoniae infection were improved through antibiotic treatment. Conclusion: The findings suggest a possible role of C. pneumoniae infection in asthma.

Clinical Study of Continuous Infection in the Urogenital System of Chlamydiae trachomatis

Objective： To analyze the causes of persistent infection of Chlamydia trachomatis in the urogenital system. Method： We followed 223 patients with Chlamydia trachomatis infection who were treated regularly. Result： After treatment, 22.87% of cases still tested positive. After one year and change of treatment regime,4.48% of cases remained positive, most of whom were female. Conclusion： The course of Chlamydia trachomatis infection in the urogenital system is varied. This diversity has many causes including immunocompetence the characteristics of chalmydia trchomatis infection and genetic resistance.

Study on Antibodies to Liver Antigens in Chinese Patients with Different Liver Diseases

In order to observe several antibodies to liver antigens in Chinese patients with different liver diseases and to discuss the characteristics of the autoantibodies in autoimmune liver diseases, from 1412 patients, detected by indirect immunofluorescence (IIF) initially, 230 patients with abnormal ALT were chosen and divided into 5 groups: ① autoimmune diseases group, 42 cases: 18 with autoimmune hepatitis (AIH), 21 with primary biliary cirrhosis (PBC), 3 with primary sclerosing cholangitis(PSC). ② HAV group, 23 cases; ③ HBV group, 70 cases; ④ HCV group, 35 cases and ⑤ Non A-E group, 60 cases. First, ANA, AMA, SMA, liver-kidney microsomal antibody (LKM) and so on were tested by IIF.Then, LKM-1, liver cytosolic-1 (LC-1), soluble liver antigen/liver pancreas (SLA/LP) and subtype of AMA (M2) as well as ANA profile such as SS-A, SS-B and dsDNA were tested by Western blot and immunoblot strips assay, respectively. The results were that among 1412 cases, those diagnosed as AIH, PBC and PSC accounted for 12.7‰, 14.9‰ and 2.1‰, respectively, of the samples being tested. 2/230 with LKM-1 and 2/230 with SLA/LP were seen in individuals infected with AIH and HCV, respectively. All patients with PBC showed AMA and M2 antibodies. No specific ANA pattern was seen in AIH by IIF but anti-actin was only found in patients with AIH. In Non A-E group, four cases were positive of AMA and M2; three had high titer of SMA and other 4 had SS-A, SS-B or dsDNA antibodies, etc. It was concluded that the detection of anti-liver antigens, ANA profile and AMA subtypes were helpful for the diagnosis of autoimmune liver diseases and overlap syndromes. In patients with Non A-E hepatitis, the diagnosis of PBC or AIH should be taken into consideration.

PRESENCE OF ANTILAMIN ANTIBODIES IN SERA OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

In this study, we characterized specifically-stained sera from patients with systemic lupus erythematosus (SLE) which had been shown to display the homogeneous or peripheral region of nuclei by indirect immunofluorescence (IIF). By western blotting, we demonstrated that in some cases there was a correlation between the peripheral or homogenous. IIF staining of nuclei by sera from patients with SLE and the presence of autoantibodies to lamins. Here we first report the presence of 2. 2% anti-lamin autoantibodies in the sera among the 174 patients with SLE in China.

Identification of the Epitopes of Monoclonal Antibodies against P74 of Helicoverpa armigera Nucleopolyhedrovirus

P74 is a per os infectivity factor of baculovirus.Here,we report the production of three monoclonal antibodies (mAbs),denoted as 20D9,20F9 and 21E1,raised against P74 of Helicoverpa armigera nucleopolyhedrovirus (HearNPV),and the identification of their recognition epitopes.The full-length P74,without the transmembrane domains at the C-terminus,was first divided into three segments (N,M and C,respectively),based on the proposed cleavage model for the protein,which were then expressed individually.Western blot analyses revealed specific cross-reactions with the N fragment,for both 20D9 and 21E1.Extensive truncation,followed by prokaryotic expression,of the P74 N fragment was then performed in order to screen for linear epitopes of P74.The recognition regions of 20D9 and 21E1 were revealed to be localized at R144-T153 and T199-C219,respectively.In addition,immunofluorescence microscopy indicated that 20D9 and 20F9 could recognize native P74 in HearNPV-infected cells.These findings will facilitate further investigations of the proteolytic processing of HearNPV P74,and of its involvement in virus-host interactions.

Presence of Alternaria in Scalp of Patients with Alopecia Areata： Triggering Factor or Coexistence？

AA （Alopecia areata） is the most frequent cause of inflammation-induced hair loss, affecting 0.1 to 0.2% of population worldwide. The development of organ-specific autoimmune reactions directed against anagen hair follicles seems to play a key role in the pathogenesis of alopecia areata. However, the triggering antigen（s） responsible for inducing autoimmune phenomena in these individuals remain unknown. Viral, bacterial or fungal pathogens have been implied as possible triggering factors of autoimmune reactions. The present study aims to identify the role of dematiaceous fungi in the pathogenesis of alopecia areata. 30 patients diagnosed clinically as alopecia areata and 30 normal age matched persons have undergone mycological examination. Mycology examination of the epidermal scrapings was done by DME （direct microscopic examination）, culture on SDA （sabouraud＇s dextrose agar） and imaging. There is significantly higher percentage of positive results for Alternaria species by culture on sabouraud＇s agar in patients group （20%） compared to controls （13.3%） P-value 〈 0.05. The possible role of Alternaria antigens （e.g. antigens involved in melanin synthesis） in triggering autoimmunity in alopecia areata still needs further research on a wider scale of cases.

microRNA-mediated R gene regulation: molecular scabbards for double-edged swords

Plant resistance(R) proteins are immune receptors that recognize pathogen effectors and trigger rapid defense responses, namely effector-triggered immunity. R protein-mediated pathogen resistance is usually race specific. During plant-pathogen coevolution,plant genomes accumulated large numbers of R genes. Even though plant R genes provide important natural resources for breeding disease-resistant crops, their presence in the plant genome comes at a cost. Misregulation of R genes leads to developmental defects, such as stunted growth and reduced fertility. In the past decade, many microRNAs(miRNAs) have been identified to target various R genes in plant genomes. miRNAs reduce R gene levels under normal conditions and allow induction of R gene expression under various stresses. For these reasons, we consider R genes to be double-edged "swords" and miRNAs as molecular "scabbards". In the present review, we summarize the contributions and potential problems of these "swords" and discuss the features and production of the "scabbards", as well as the mechanisms used to pull the "sword" from the "scabbard"when needed.

The role of iron homeostasis in remodeling immune function and regulating inflammatory disease

The essential trace element iron regulates a wide range of biological processes in virtually all living organisms.Because both iron deficiency and iron overload can lead to various pathological conditions,iron homeostasis is tightly regulated,and understanding this complex process will help pave the way to developing new therapeutic strategies for inflammatory disease.In recent years,significant progress has been made with respect to elucidating the roles of iron and iron-related genes in the development and maintenance of the immune system.Here,we review the timing and mechanisms by which systemic and cellular iron metabolism are regulated during the inflammatory response and during infectious disease,processes in which both the host and the pathogen compete for iron.We also discuss the evidence and implications that immune cells such as macrophages,T cells,and B cells require sufficient amounts of iron for their proliferation and for mediating their effector functions,in which iron serves as a co-factor in toll-like receptor 4(TLR4)signaling,mitochondrial respiration,posttranslational regulation,and epigenetic modification.In addition,we discuss the therapeutic implications of targeting ferroptosis,iron homeostasis and/or iron metabolism with respect to conferring protection against pathogen infection,controlling inflammation,and improving the efficacy of immunotherapy.