Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with eryt...Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with erythrocyte selenium. Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), and 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P< 0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r= 0.625, P< 0.05), as well as serum IgA (r= 0.462, P< 0.05). In addition, a moderate correlation between the serum IgA and CD4+ percentage (r= 0.130, P> 0.05) was found. Conclusion These results suggested that children in KAA had a comparably low cellular immunity level and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in Kashin-Beck disease patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.展开更多
[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Meth...[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Methods]A total of 120 one-day old female Hyline brown laying hens were randomly divided into 4 groups,30 hens for each group.The chicks in group 1 were subcutaneously injected with NRTUAs and fed on the diet containing with ABP;the chicks in group 2 were subcutaneously injected with NRTUAs;the chicks in group 3 were subcutaneously injected with equal volume of PBS,and fed on the diet containing with ABP;the chicks in group 4 were subcutaneously injected with equal volume of PBS.The body weight of chicks in each group was counted at the 21^(st),42^(nd),84^(th)and 112^(th)week.During this period,blood samples were collected from chicks in each group at 0,7,14,21,28 and 35 d post immunization against Newcastle disease(ND),and serum was separated to detect the antibody titer of ND.[Results]The combined application of NRTUAs and ABP had no effect on growth of chicks,but promoted the humoral immune response of chicks,significantly improved the ND antibody level of chicks,and could maintain high levels of antibodies in the body for a long time.[Conclusions]The study lays a theoretical foundation for further developing the clinical application of NRTUAs and ABP.展开更多
Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin l...Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.展开更多
The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-2...The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-260 g were divided into five groups and reared in 15 tanks with closed circuiting culture system. The animals were fed 5 diets: basal diet only (control) or supplemented of the basal diet with C. butyricum at doses of 10^3 (CB1), 10^5 (CB2), 10^7 (CB3) or 10^9 (CB4) CFU/g. Compared with the control, the serum phenoloxidase activity was significantly increased by the supplementation (P〈0.05), acid phosphatases activity was increased significantly (P〈0.05) at the doses of 10^9 CFU/g. Serum lysozyme activity peaked at dose of 10^7 CFU/g and in the skin mucus at dose of 10^9 CFU/g. Immunoglobulin M level in the serum and skin mucus was increased except at dose of 10^3 CFU/g (P〈0.05). The growth at the dose of 10^9 CFU/g was higher than that of the control (P〈0.05). It is concluded that supplementation of C. butyricum can mediate the humoral immune responses and improve the growth performance in Miichthys miiuy.展开更多
Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental fac...Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.展开更多
C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity ...C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity in insects.In this study,we report a novel dual carbohydrate-recognition domain(CRD)CTL from Plutella xylostella which we designate PxIML.PxIML is a protein with a 969 bp open reading frame(ORF)encoding 322 amino acids,containing a signal peptide and a dual-CRD with EPN(Glu_(124)-Pro_(125)-Asn_(126))and QPD(Gln_(274)-Pro_(275)-Asp_(276))motifs.The expression of PxIML mRNA in the fat body was significantly higher than in hemocytes and midgut.The relative expression levels of PxIML in the whole insect and the fat body were significantly inhibited after infection with Bacillus thuringiensis 8010(Bt8010)at 18 h,while they were significantly upregulated after infection with Serratia marcescens IAE6 or Pichia pastoris.The recombinant PxIML(rPxIML)protein could bind to the tested pathogen-associated molecular patterns(PAMPs),and the bacteria of Enterobacter sp.IAE5,S.marcescens IAE6,Staphylococcus aureus,Escherichia coli BL21,and Bt8010 in a Ca^(2+)-dependent manner,however,it showed limited binding to the fungus,P.pastoris.The rPxIML exhibited strong activity in the presence of Ca^(2+) to agglutinate Bt8010,Enterobacter sp.IAE5 and S.aureus,but it only weakly agglutinated with E.coli BL21,and could not agglutinate with S.marcescens IAE6 or P.pastoris.Furthermore,the rPxIML could bind to hemocytes,promote the adsorption of hemocytes to beads,and enhance the phenoloxidase(PO)activity and melanization of P.xylostella.Our results suggest that PxIML plays an important role in pathogen recognition and in mediating subsequent humoral and cellular immunity of P.xylostella.展开更多
Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71(SP70) without His-tagged.Then evaluating whether the VLPs could efficiently evoke ...Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71(SP70) without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.展开更多
[ Objective] To study the effects of different oligosaccharides on immunity and production performance of piglets.[ Method] A total of 75 Yorkshire x Rongchang piglets were assigned into five groups, 15 in each group....[ Objective] To study the effects of different oligosaccharides on immunity and production performance of piglets.[ Method] A total of 75 Yorkshire x Rongchang piglets were assigned into five groups, 15 in each group. Isomalto-oligosaccharide ( IMO), fructo-oligosaccharide ( FOS), mannan-oligosacchadde (MOS), and mixed oligosacchadde were supplemented to basal diet (7.5 g/kg), respectively. The control group was also set. The experimental period lasted for 53 d. The clinic symptoms and diarrhea were observed. All piglets were weighed once a week. Feed intake was also recorded. Blood was collected via precaval vein for determination of immunology indexes at the age of 30 and 60 d, respectively. [ Result] The IMO and FOS enhanced cellular immunity of 30-day-old piglets significantly (P 〈 0.05), and the IMO also enhanced their humoral immunity. The MOS enhanced cellular immunity and humoral immunity of 60-day-old piglets significantly (P 〈 0.05). It also improved production performance largest, and its diarrhea rate was the lowest. [ Conclusion] Different oligosaccharides have various effects on immunity and production performance of oiolets.展开更多
It is well known that IL4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL4 genemodified tumor vaccine were investigated. The mice were va...It is well known that IL4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL4 genemodified tumor vaccine were investigated. The mice were vaccinated with the IL4 genemodified B16 melanoma cells. Then the proliferative capacity of the splenic lymphocytes, the levels of the antibodies in the murine serum against wildtype B16 cells and the cytotoxicity of the serum to wildtype melanoma cells were detected. Our data showed that the LPSinduced proliferation of the splenic lymphocytes from the mice vaccinated with the IL4 genemodified tumor vaccine increased more significantly than that from mice vaccinated with wildtype tumor vaccine. The cytotoxicity of the serum to wildtype melanoma cells also increased markedly when detected. It was also observed that the number of pulmonary metastases decreased more obviously when the mice were intravenously injected with the mixture of wildtype B16 cells and the serum from the mice vaccinated with the IL4 genemodified B16 cells. Our data demonstrated that humoral immunity might contribute to the antitumor effect of IL4 gene therapy.展开更多
Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid p...Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN-γ cells in CD4 + and CD8 + subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4 + IL4 + cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immune responses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.展开更多
With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune respon...With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.展开更多
[ Objective] The paper was to study the immune enhancement of ATRA on Newcastle Disease (ND) vaccine. [ Method ] The 1-day-old AA broilers were treated with ATRA at the doses of I and 5 p.mol/kg, respectively. At 7 ...[ Objective] The paper was to study the immune enhancement of ATRA on Newcastle Disease (ND) vaccine. [ Method ] The 1-day-old AA broilers were treated with ATRA at the doses of I and 5 p.mol/kg, respectively. At 7 and 28 days of age, broilers in drug control group, low dose group and high dose group were immunized with ND vaccine by intranasal and eye immunization approach. At 7, 14, 21, 28, 35, 42 and 49 clays of age, seven chickens were randomly se- lected from each group and weighed. The thymus, spleen, bursa of fabrieius and serum were collected for calculating immune organ index of thymus, spleen and bursa of fabricius. The ND specific antibody titers in serum were determined with HI test. [Result] ATRA promoted the growth of thymus, spleen and bursa of fabricius, and improved the immune organ index and ND specific antibody titers of chicks. [ Conclusion] ATRA enhanced the humoral immune response of chicks, and ATRT at the dose of 5 μmol/kg presented more prominent immune enhancement effect on ND vaccine.展开更多
[Objective] The study was aimed to investigate the effects of NS series composite lactobacillus preparation on production performance and some immune indexes of sows. [Method] The sows were fed on the diets supplement...[Objective] The study was aimed to investigate the effects of NS series composite lactobacillus preparation on production performance and some immune indexes of sows. [Method] The sows were fed on the diets supplemented with the NS series composite lactobacillus prepara- tion, and the changes of production performance, plasma biochemical indexes, levels of IgG, IgA and IgM in serum and colostrum, and T lympho- cyte subpopulations were detected. [ Result] When the NS series composite lactobacillus preparation was supplemented to the sow diet at a propor- tion of 0.2%, the average weaning litter weight at 21 days old was significantly increased. The serum contents of total protein and glucose as well as the serum activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and superoxide dismutase (SOD) were significantly in- creased after 30 d post delivery. Moreover, the levels of IgG, IgA and IgM in serum and colostrum of sows were significantly increased at the time of delivery and after 30 d post delivery. The antibodies in colostrum could be maintained at high levels. The percentage of CD3 * and CD4~ |ympho- cyte subpopulations was also increased after supplementation with the NS series composite lactobacillus preparation at a proportion of 0.2%. [ (Con- des'ion] The NS series composite lactobacillus preparation can improve performance, promote growth and metabolism, and enhance humoral and cellular immunity in sows.展开更多
Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct sig...Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways.However,their clinical application is hindered by uncontrolled systemic inflammatory reactions.Therefore,it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy.In this study,we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes(1V209-Cho-Lip^(+))to mitigate undesired side effects.Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8^(+)T cells.The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip^(+)in tumor vaccines.Following immunization with 1V209-Cho-Lip^(+)+OVA,we observed a pronounced"depot effect"and enhanced trafficking to secondary lymphoid organs.Prophylactic vaccination with 1V209-Cho-Lip^(+)^(+)OVA significantly delays tumor development,prolongs mouse survival,and establishes durable immunity against tumor recurrence.Additionally,1V209-Cho-Lip^(+)+OVA,while used therapeutic tumor vaccine,has demonstrated its efficacy in inhibiting tumor progression,and when combined with anti-PD-1,it further enhances antitumor effects.Therefore,the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.展开更多
Objective To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. Methods ICR mice were exposed to different doses of ...Objective To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells (PFCs) at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma (IFN-?) at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha (TNF-α) at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.展开更多
This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of wood...This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.展开更多
There are appreciable does of raffinose in soybean,but the impacts of raffinose on pigs are poorly investigated.We used 2 experiments to investigate the influence of soybean raffinose on growth per-formance,digestibil...There are appreciable does of raffinose in soybean,but the impacts of raffinose on pigs are poorly investigated.We used 2 experiments to investigate the influence of soybean raffinose on growth per-formance,digestibility,humoral immunity and intestinal morphology of growing pigs.In Exp.1,a total of 30 crossbred(Duroc×Landrace×Yorkshire)barrows(21.93±0.43 kg)were randomly divided into 3 groups,and were fed with the control diet,the control diets supplemented with 0.2%and 0.5%raffinose,respectively,for 21 d.Results showed that the addition of 0.2%or 0.5%raffinose reduced(P<0.05)average daily feed intake(ADFI),average daily gain(ADG)and nutrient digestibility,and dietary 0.5%raffinose increased the ratio of feed to gain(P<0.05).For serum indexes,dietary 0.5%raffinose decreased growth hormone and increased glucagon-like peptide-2,immunoglobulin G,tumor necrosis factor-α(TNF-α)and interleukin-6 concentration(P<0.05).In Exp.2,a total of 24 crossbred barrows(38.41±0.45 kg)were randomly divided into 3 groups,and were fed with the control diet(ad libitum),the raffinose diet(0.5%raffinose,ad libitum),and the control diet in the same amount as the raffinose group(feed-pair group)for 14 d,respectively.Compared with the control diet,dietary 0.5%raffinose decreased ADFI(P<0.05).Intriguingly,the raffinose group had lower ADG than the feed-pair group,lower nutrient digestibility,lower amylase activity in duodenum,lower amylase,lipase and trypsin ac-tivities in jejunum and higher TNF-αconcentration in serum compared with the other 2 groups,and a higher ratio of villus height to crypt depth compared with the control group(P<0.05).These results showed that soybean raffinose could reduce feed voluntary intake and body gain while improving in-testinal morphology without a significant negative influence on immunity.Taken together,dietary raffinose could decrease growth performance by reducing both feed intake and nutrient digestibility while inducing humoral immune response of growing pigs.展开更多
Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an ongoing pandemic that poses a great threat to human health worldwide.As the humoral immune response plays ...Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an ongoing pandemic that poses a great threat to human health worldwide.As the humoral immune response plays essential roles in disease occurrence and development,understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease.In this review,we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARSCoV-2-specific humoral immunity and the critical role of this immunity in vaccine development.Notably,serological antibody testing based on the humoral immune response can guide public health measures and control strategies;however,it is not recommended for population surveys in areas with very low prevalence.Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection,whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults.The correlations between antibody(especially neutralizing antibody)titers and protection against SARS-CoV-2 reinfection should be further examined.In addition,the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.展开更多
Animal immunity is usually impaired in obesity.We know little about the effect of being overweight or obese on the immune function of wild rodents.The present study is aimed to test the hypothesis that immunity is sup...Animal immunity is usually impaired in obesity.We know little about the effect of being overweight or obese on the immune function of wild rodents.The present study is aimed to test the hypothesis that immunity is suppressed in overweight Mongolian gerbils(Meriones unguiculatus).In the study,16 overweight(body mass:90.8-127.6 g)and 16 lean gerbils(body mass:60.5-77.7 g)were randomly selected from a total of 174 male gerbils(body mass range:55.8-144.7 g).Half of the overweight and lean males were injected with sterile saline;the others were immunochallenged(IC)with phytohaemagglutinin and keyhole limpet hemocyanin to assess cellular and humoral immunity,respectively.Body fat mass,wet and dry spleen mass,leukocyte counts,blood glucose levels and serum leptin levels were significantly higher in the overweight gerbils than in the lean gerbils.However,phytohemagglutinin response indicative of cellular immunity and immunoglobulin G concentrations was significantly lower in the IC overweight gerbils than in the IC lean gerbils.These results indicate that cellular and humoral immunity are impaired in the overweight gerbils.Excessive body fat mass,higher leukocyte counts and serum leptin levels imply that overweight gerbils are in a low grade inflammatory state.展开更多
Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early...Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.展开更多
基金ThisresearchwassupportedbytheNationalNaturalScienceFoundationofChina(No.39770667),theScience&TechnologyDevelopmentFoundationofShaanxiProvince(No.2001SM82)and china and belgium cooperated study
文摘Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with erythrocyte selenium. Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), and 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P< 0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r= 0.625, P< 0.05), as well as serum IgA (r= 0.462, P< 0.05). In addition, a moderate correlation between the serum IgA and CD4+ percentage (r= 0.130, P> 0.05) was found. Conclusion These results suggested that children in KAA had a comparably low cellular immunity level and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in Kashin-Beck disease patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.
基金Supported by National Natural Science Foundation of China(31902277)。
文摘[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Methods]A total of 120 one-day old female Hyline brown laying hens were randomly divided into 4 groups,30 hens for each group.The chicks in group 1 were subcutaneously injected with NRTUAs and fed on the diet containing with ABP;the chicks in group 2 were subcutaneously injected with NRTUAs;the chicks in group 3 were subcutaneously injected with equal volume of PBS,and fed on the diet containing with ABP;the chicks in group 4 were subcutaneously injected with equal volume of PBS.The body weight of chicks in each group was counted at the 21^(st),42^(nd),84^(th)and 112^(th)week.During this period,blood samples were collected from chicks in each group at 0,7,14,21,28 and 35 d post immunization against Newcastle disease(ND),and serum was separated to detect the antibody titer of ND.[Results]The combined application of NRTUAs and ABP had no effect on growth of chicks,but promoted the humoral immune response of chicks,significantly improved the ND antibody level of chicks,and could maintain high levels of antibodies in the body for a long time.[Conclusions]The study lays a theoretical foundation for further developing the clinical application of NRTUAs and ABP.
文摘Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.
基金Project supported by the Bureau of Science and Technology of Zhejiang Province (No. 2004201), China and the Youth Fund of Ningbo City (No. 2004A620008), China
文摘The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-260 g were divided into five groups and reared in 15 tanks with closed circuiting culture system. The animals were fed 5 diets: basal diet only (control) or supplemented of the basal diet with C. butyricum at doses of 10^3 (CB1), 10^5 (CB2), 10^7 (CB3) or 10^9 (CB4) CFU/g. Compared with the control, the serum phenoloxidase activity was significantly increased by the supplementation (P〈0.05), acid phosphatases activity was increased significantly (P〈0.05) at the doses of 10^9 CFU/g. Serum lysozyme activity peaked at dose of 10^7 CFU/g and in the skin mucus at dose of 10^9 CFU/g. Immunoglobulin M level in the serum and skin mucus was increased except at dose of 10^3 CFU/g (P〈0.05). The growth at the dose of 10^9 CFU/g was higher than that of the control (P〈0.05). It is concluded that supplementation of C. butyricum can mediate the humoral immune responses and improve the growth performance in Miichthys miiuy.
文摘Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.
基金the project of the National Key R&D Program of China(2017YFE0122000)the National Natural Science Foundation of China(31871968)the Natural Science Foundation of Fujian Province,China(2018J01614).
文摘C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity in insects.In this study,we report a novel dual carbohydrate-recognition domain(CRD)CTL from Plutella xylostella which we designate PxIML.PxIML is a protein with a 969 bp open reading frame(ORF)encoding 322 amino acids,containing a signal peptide and a dual-CRD with EPN(Glu_(124)-Pro_(125)-Asn_(126))and QPD(Gln_(274)-Pro_(275)-Asp_(276))motifs.The expression of PxIML mRNA in the fat body was significantly higher than in hemocytes and midgut.The relative expression levels of PxIML in the whole insect and the fat body were significantly inhibited after infection with Bacillus thuringiensis 8010(Bt8010)at 18 h,while they were significantly upregulated after infection with Serratia marcescens IAE6 or Pichia pastoris.The recombinant PxIML(rPxIML)protein could bind to the tested pathogen-associated molecular patterns(PAMPs),and the bacteria of Enterobacter sp.IAE5,S.marcescens IAE6,Staphylococcus aureus,Escherichia coli BL21,and Bt8010 in a Ca^(2+)-dependent manner,however,it showed limited binding to the fungus,P.pastoris.The rPxIML exhibited strong activity in the presence of Ca^(2+) to agglutinate Bt8010,Enterobacter sp.IAE5 and S.aureus,but it only weakly agglutinated with E.coli BL21,and could not agglutinate with S.marcescens IAE6 or P.pastoris.Furthermore,the rPxIML could bind to hemocytes,promote the adsorption of hemocytes to beads,and enhance the phenoloxidase(PO)activity and melanization of P.xylostella.Our results suggest that PxIML plays an important role in pathogen recognition and in mediating subsequent humoral and cellular immunity of P.xylostella.
基金supported by the National Science-technology Support Plan Projects 'The development of EV71 genetic engineering vaccine'[2008BAI69B02]
文摘Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71(SP70) without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.
基金funded by the Technology Programme Project of Zhongshan City (China) (20073A159)the Open Project of the Key Laboratory of Animal Nutrition and Feed of Yunnan Province
文摘[ Objective] To study the effects of different oligosaccharides on immunity and production performance of piglets.[ Method] A total of 75 Yorkshire x Rongchang piglets were assigned into five groups, 15 in each group. Isomalto-oligosaccharide ( IMO), fructo-oligosaccharide ( FOS), mannan-oligosacchadde (MOS), and mixed oligosacchadde were supplemented to basal diet (7.5 g/kg), respectively. The control group was also set. The experimental period lasted for 53 d. The clinic symptoms and diarrhea were observed. All piglets were weighed once a week. Feed intake was also recorded. Blood was collected via precaval vein for determination of immunology indexes at the age of 30 and 60 d, respectively. [ Result] The IMO and FOS enhanced cellular immunity of 30-day-old piglets significantly (P 〈 0.05), and the IMO also enhanced their humoral immunity. The MOS enhanced cellular immunity and humoral immunity of 60-day-old piglets significantly (P 〈 0.05). It also improved production performance largest, and its diarrhea rate was the lowest. [ Conclusion] Different oligosaccharides have various effects on immunity and production performance of oiolets.
文摘It is well known that IL4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL4 genemodified tumor vaccine were investigated. The mice were vaccinated with the IL4 genemodified B16 melanoma cells. Then the proliferative capacity of the splenic lymphocytes, the levels of the antibodies in the murine serum against wildtype B16 cells and the cytotoxicity of the serum to wildtype melanoma cells were detected. Our data showed that the LPSinduced proliferation of the splenic lymphocytes from the mice vaccinated with the IL4 genemodified tumor vaccine increased more significantly than that from mice vaccinated with wildtype tumor vaccine. The cytotoxicity of the serum to wildtype melanoma cells also increased markedly when detected. It was also observed that the number of pulmonary metastases decreased more obviously when the mice were intravenously injected with the mixture of wildtype B16 cells and the serum from the mice vaccinated with the IL4 genemodified B16 cells. Our data demonstrated that humoral immunity might contribute to the antitumor effect of IL4 gene therapy.
文摘Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN-γ cells in CD4 + and CD8 + subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4 + IL4 + cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immune responses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.
基金supported by the National Natural Science Foundation of China(U1703118)Natural Science Foundation of Jiangsu Province(No.BK20181364)+6 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.19KJA310003)Scientific Research Foundation of Jiangsu health and Health Committee(No.H2018087)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Jiangsu Shuangchuang ProgramOpen Funds of the State Key Laboratory for Chemo/Biosensing and Chemometrics(2016015)Open project of the National Laboratory of Biomacromolecules(2017kf05)the cooperative project between Southeast University and Nanjing Medical University(2018DN0004)Jiangsu Specially-Appointed Professor project,China。
文摘With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.
基金Supported by Science and Technology Development Fund of Tianjin Agricultural University(2013N09)"Veterinary Biological Technology"Innovation Team Project of Colleges and Universities in Tianjin(TD12-5019)+1 种基金Innovative Team Training Program Fund of Colleges and Universities in Tianjin(TNTD2015015)Development Program Leading Education Reform and Innovation of College Teachers at Tianjin Agricultural University(20171003)
文摘[ Objective] The paper was to study the immune enhancement of ATRA on Newcastle Disease (ND) vaccine. [ Method ] The 1-day-old AA broilers were treated with ATRA at the doses of I and 5 p.mol/kg, respectively. At 7 and 28 days of age, broilers in drug control group, low dose group and high dose group were immunized with ND vaccine by intranasal and eye immunization approach. At 7, 14, 21, 28, 35, 42 and 49 clays of age, seven chickens were randomly se- lected from each group and weighed. The thymus, spleen, bursa of fabrieius and serum were collected for calculating immune organ index of thymus, spleen and bursa of fabricius. The ND specific antibody titers in serum were determined with HI test. [Result] ATRA promoted the growth of thymus, spleen and bursa of fabricius, and improved the immune organ index and ND specific antibody titers of chicks. [ Conclusion] ATRA enhanced the humoral immune response of chicks, and ATRT at the dose of 5 μmol/kg presented more prominent immune enhancement effect on ND vaccine.
基金funded by the Key Technologies R&D Program of Guangxi of China (0992014-5)
文摘[Objective] The study was aimed to investigate the effects of NS series composite lactobacillus preparation on production performance and some immune indexes of sows. [Method] The sows were fed on the diets supplemented with the NS series composite lactobacillus prepara- tion, and the changes of production performance, plasma biochemical indexes, levels of IgG, IgA and IgM in serum and colostrum, and T lympho- cyte subpopulations were detected. [ Result] When the NS series composite lactobacillus preparation was supplemented to the sow diet at a propor- tion of 0.2%, the average weaning litter weight at 21 days old was significantly increased. The serum contents of total protein and glucose as well as the serum activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and superoxide dismutase (SOD) were significantly in- creased after 30 d post delivery. Moreover, the levels of IgG, IgA and IgM in serum and colostrum of sows were significantly increased at the time of delivery and after 30 d post delivery. The antibodies in colostrum could be maintained at high levels. The percentage of CD3 * and CD4~ |ympho- cyte subpopulations was also increased after supplementation with the NS series composite lactobacillus preparation at a proportion of 0.2%. [ (Con- des'ion] The NS series composite lactobacillus preparation can improve performance, promote growth and metabolism, and enhance humoral and cellular immunity in sows.
基金supported by the National Science Foundation for Excellent Young Scholars(32122052,China)National Natural Science Foundation Regional Innovation and Development(No.U19A2003,China).
文摘Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways.However,their clinical application is hindered by uncontrolled systemic inflammatory reactions.Therefore,it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy.In this study,we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes(1V209-Cho-Lip^(+))to mitigate undesired side effects.Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8^(+)T cells.The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip^(+)in tumor vaccines.Following immunization with 1V209-Cho-Lip^(+)+OVA,we observed a pronounced"depot effect"and enhanced trafficking to secondary lymphoid organs.Prophylactic vaccination with 1V209-Cho-Lip^(+)^(+)OVA significantly delays tumor development,prolongs mouse survival,and establishes durable immunity against tumor recurrence.Additionally,1V209-Cho-Lip^(+)+OVA,while used therapeutic tumor vaccine,has demonstrated its efficacy in inhibiting tumor progression,and when combined with anti-PD-1,it further enhances antitumor effects.Therefore,the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.
基金the Scientific Research Foundation of Health Bureau of Zhejiang Province (No. 2006c151)
文摘Objective To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells (PFCs) at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma (IFN-?) at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha (TNF-α) at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.
基金Supported by contract N01-AI-05399 to the College of Veterinary Medicine, Cornell University from the National Institute of Allergy and Infectious Diseases. PC and SM also have been supported by contract N01-AI-95390 to the Georgetown University Medical Center, Georgetown University from the National Institute of Allergy and Infectious Diseases
文摘This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.
基金the National Natural Science Foundation of China,No.31730091
文摘There are appreciable does of raffinose in soybean,but the impacts of raffinose on pigs are poorly investigated.We used 2 experiments to investigate the influence of soybean raffinose on growth per-formance,digestibility,humoral immunity and intestinal morphology of growing pigs.In Exp.1,a total of 30 crossbred(Duroc×Landrace×Yorkshire)barrows(21.93±0.43 kg)were randomly divided into 3 groups,and were fed with the control diet,the control diets supplemented with 0.2%and 0.5%raffinose,respectively,for 21 d.Results showed that the addition of 0.2%or 0.5%raffinose reduced(P<0.05)average daily feed intake(ADFI),average daily gain(ADG)and nutrient digestibility,and dietary 0.5%raffinose increased the ratio of feed to gain(P<0.05).For serum indexes,dietary 0.5%raffinose decreased growth hormone and increased glucagon-like peptide-2,immunoglobulin G,tumor necrosis factor-α(TNF-α)and interleukin-6 concentration(P<0.05).In Exp.2,a total of 24 crossbred barrows(38.41±0.45 kg)were randomly divided into 3 groups,and were fed with the control diet(ad libitum),the raffinose diet(0.5%raffinose,ad libitum),and the control diet in the same amount as the raffinose group(feed-pair group)for 14 d,respectively.Compared with the control diet,dietary 0.5%raffinose decreased ADFI(P<0.05).Intriguingly,the raffinose group had lower ADG than the feed-pair group,lower nutrient digestibility,lower amylase activity in duodenum,lower amylase,lipase and trypsin ac-tivities in jejunum and higher TNF-αconcentration in serum compared with the other 2 groups,and a higher ratio of villus height to crypt depth compared with the control group(P<0.05).These results showed that soybean raffinose could reduce feed voluntary intake and body gain while improving in-testinal morphology without a significant negative influence on immunity.Taken together,dietary raffinose could decrease growth performance by reducing both feed intake and nutrient digestibility while inducing humoral immune response of growing pigs.
基金supported by the Major National S&T Program Grant(2017ZX10202203 and 2017ZX10302201 to AH)the Science&Technology Commission of China,the Emergency Project(cstc2020jscx-fyzx0053 to AH)+3 种基金the Science&Technology Commission of Chongqing,the National Natural Science Foundation of China(82002131 to YL)the Natural Science Foundation Project of CQ CSTC(cstc2020jcyjmsxmX0081 to YL)the foundation(KJCXZD2020018 to YL,CYS21244 to JZ)the Chongqing Municipal Education Commission,and the COVID-19 Emergency Project(CQMUNCP0207 to YL)from Chongqing Medical University。
文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an ongoing pandemic that poses a great threat to human health worldwide.As the humoral immune response plays essential roles in disease occurrence and development,understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease.In this review,we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARSCoV-2-specific humoral immunity and the critical role of this immunity in vaccine development.Notably,serological antibody testing based on the humoral immune response can guide public health measures and control strategies;however,it is not recommended for population surveys in areas with very low prevalence.Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection,whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults.The correlations between antibody(especially neutralizing antibody)titers and protection against SARS-CoV-2 reinfection should be further examined.In addition,the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.
基金This study was supported by grants to DHW from the National Science and Technology Ministry Project(No.2007BC109103)the National Natural Science Foundation of China(30625009).
文摘Animal immunity is usually impaired in obesity.We know little about the effect of being overweight or obese on the immune function of wild rodents.The present study is aimed to test the hypothesis that immunity is suppressed in overweight Mongolian gerbils(Meriones unguiculatus).In the study,16 overweight(body mass:90.8-127.6 g)and 16 lean gerbils(body mass:60.5-77.7 g)were randomly selected from a total of 174 male gerbils(body mass range:55.8-144.7 g).Half of the overweight and lean males were injected with sterile saline;the others were immunochallenged(IC)with phytohaemagglutinin and keyhole limpet hemocyanin to assess cellular and humoral immunity,respectively.Body fat mass,wet and dry spleen mass,leukocyte counts,blood glucose levels and serum leptin levels were significantly higher in the overweight gerbils than in the lean gerbils.However,phytohemagglutinin response indicative of cellular immunity and immunoglobulin G concentrations was significantly lower in the IC overweight gerbils than in the IC lean gerbils.These results indicate that cellular and humoral immunity are impaired in the overweight gerbils.Excessive body fat mass,higher leukocyte counts and serum leptin levels imply that overweight gerbils are in a low grade inflammatory state.
基金This work was supported by the financial support of the PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to R.B.The financial support of the PID2019-103899RB-I00(Ministerio de Ciencia e Innovación)Research Project and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid(S2018/NMT-4349)to S.C.are gratefully acknowledged.+3 种基金G.D.acknowledges the financial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de InnovaciónThe FPU predoctoral contract to A.M.-C.is supported by the Spanish Ministerio de Educación,Cultura y Deporte.G.S.-F.is recipient of a predoctoral contract(1193818 N)supported by The Flanders Research Foundation(FWO).M.A.-N.was supported by a contract of the Programa Operativo de Empleo Juvenily la Iniciativa de Empleo Juvenil(YEI)with the participation of the Consejería de Educación,Juventud y Deporte de la Comunidad de Madrid y del Fondo Social EuropeoThe predoctoral contract from the Spanish Ministerio de Economía y Competitividad(BES-2016-076606,E.P.)Talento-Contract from Comunidad de Madrid(2019-T2/IND-15965,R.M.T.-R.)are also gratefully acknowledged.
文摘Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.