scholarly journals Characterization of the Pathology, Biochemistry, and Immune Response in Kunming (KM) Mice Following Fasciola gigantica Infection

2022 ◽  
Vol 11 ◽  
Author(s):  
Xuefang Mei ◽  
Yaoyao Zhang ◽  
Chenyu Quan ◽  
Yiying Liang ◽  
Weiyi Huang ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
Serum Levels ◽  
Serum Biochemistry ◽  
Fasciola Gigantica ◽  
Interleukin 4 ◽  
T Helper 1 ◽  
Igg Antibody ◽  
Km Mice ◽  
Cellular Immune

As a putative model of Fasciola gigantica infection, detailed data in Kunming (KM) mice infected with F. gigantica are lacking. In this study, KM mice were orally infected with 15 metacercaria for 8 weeks. Macroscopic and microscopic changes, serum biochemistry, cytokine responses, and changes in parasite-specific immunoglobulin G (IgG) antibody levels were monitored at 1, 3, 5, 7, and 8 weeks post-infection (wpi), respectively. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased after infection, while that of albumin (ALB) decreased, which was positively correlated with the degree of liver damage. Between 5 and 7 wpi, the mice showed symptoms of anemia and weight loss, possibly caused by the decrease of alkaline phosphatase (ALP). Moreover, the changing tendencies of the levels of globulin (GLB) and parasite-specific IgG antibody were similar, suggesting a potential correlation between GLB production and adaptive immune response in the host. Coordinated variations in interferon gamma (IFN-γ) and interleukin 4 (IL-4) indicated a mixed T helper 1 (Th1)/Th2 cellular immune response. Furthermore, the serum IgG antibody increased after infection and peaked at 5 wpi, and it was positively correlated with the average parasite burdens. The worms collected from mice were approximately 1 cm in length at 8 wpi, their digestive and reproductive systems were well developed, and no eggs were found in the uterus. To the best of our knowledge, this is the first report describing detailed histological, biochemical, and immunological indices in KM mice infected with F. gigantica, which provides basic information on KM mice against infection with F. gigantica.

scholarly journals Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

2020 ◽  
Vol 7 ◽  
Author(s):  
Mark Nomden ◽  
Leonie Beljaars ◽  
Henkjan J. Verkade ◽  
Jan B. F. Hulscher ◽  
Peter Olinga
Keyword(s):  
Immune Response ◽  
Liver Fibrosis ◽  
Pulmonary Fibrosis ◽  
Matrix Metalloproteinase ◽  
Biliary Atresia ◽  
Adaptive Immune Response ◽  
Cell Contact ◽  
T Helper 1 ◽  
Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

scholarly journals An Exaggerated Monocyte-Derived Cytokine Response to Candida Hyphae in Patients With Recurrent Vulvovaginal Candidiasis

2020 ◽  
Author(s):  
Diletta Rosati ◽  
Mariolina Bruno ◽  
Martin Jaeger ◽  
Bart-Jan Kullberg ◽  
Frank van de Veerdonk ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Adaptive Immune Response ◽  
Vulvovaginal Candidiasis ◽  
T Helper 1 ◽  
Recurrent Vulvovaginal Candidiasis ◽  
Tnf Α ◽  
Group A ◽  
Factor Α

Abstract Background Recurrent vulvovaginal candidiasis (RVVC) affects up to 8% of women. The immunopathogenesis is poorly understood but it has been suggested that RVVC might be due to dysregulated innate immune response. The aim of this study was to compare cytokine profiles in stimulated primary mononuclear cells (PBMCs) from RVVC and healthy individuals. Methods PBMCs isolated from RVVC patients (n = 24) and healthy volunteers (n = 30) were stimulated with unspecific and pathogen-specific antigens. Cytokine production was assessed after 24 hours, 48 hours, and 7 days using ELISA. Results No significant differences in cytokine production were found in T helper 1 (Th1), Th2, and Th17 immunity in response to both unspecific and pathogen-specific stimulations. Tumor necrosis factor-α (TNF-α) production in response to C. albicans hyphae was significantly higher in patients than controls and within the patient group, a significant positive correlation was found between interleukin-1β (IL-1β) and both TNF-α and IL-6. Both IL-1β/IL-1Ra and TNF-α/IL-10 ratios in Candida hyphae-stimulated PBMCs were significantly higher in patients than controls. Conclusions Women affected by RVVC showed increased monocytes-derived cytokine production, which might contribute to an exaggerated vaginal immune response to Candida hyphae. RVVC patients show no defective Th-dependent adaptive immune response upon Candida stimulation.

scholarly journals Th2–mediated host protective immunity to intestinal nematode infections

1997 ◽  
Vol 352 (1359) ◽  
pp. 1377-1384 ◽  
Author(s):  
R. K. Grencis
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Adaptive Immune Response ◽  
Transgenic Animals ◽  
Model Systems ◽  
Interleukin 4 ◽  
Laboratory Model ◽  
Intestinal Helminth ◽  
Effector Mechanisms

Despite many years of study, relatively little is known about the effector mechanisms that operate against intestine–dwelling nematodes. Most of the current understanding comes from studies of laboratory model systems in rodents. It is clear that when an intestinal helminth infection takes place the immune system generates a strong Th2–mediated response, which regulates a variety of responses characteristic of helminth infections such as eosinophilia, intestinal mastocytosis and elevated IgE production. The ability to modulate the host's immune response in vivo with cytokine–specific monoclonal antibodies and recombinant cytokines, together with the use of animals with disruption of key genes involved in the immune response, have provided powerful tools with which to dissect the potential effector mechanisms operating. In the absence of a T–cell compartment the host is unable to expel the parasite. If a Th1–dominated response is generated, protective immunity is almost universally compromised. Thus, it would appear that some aspect of Th2–mediated response controls effector mechanisms. Although it is clear that for some infections the mast cell appears to be involved in protection, probably through the generation of a non–specific inflammatory response, how these cells become activated remains unclear. Data from infections in transgenic animals suggest that activation is not through the high–affinity receptor for IgE. Such studies also call into doubt the importance of conventional interactions between effector leucocytes and antibody. There is little evidence to support a protective role for eosinophilia in any system. New data also imply that , although interleukin 4 (IL–4) is generally important (and can exert effects independent of an adaptive immune response), it is not always sufficient to mediate protection; other Th2 cytokines (e.g. IL–13) may warrant closer investigation. It is apparent that a number of potential Th2–controlled effector mechanisms (some of which may be particularly important at mucosal surfaces) remain to be explored. Overall, it is likely that worm expulsion is the result of a combination of multiple mechanisms, some of which are more critical to some species of parasite than to others.

scholarly journals Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1273
Author(s):  
Kirill Vasilyev ◽  
Anna-Polina Shurygina ◽  
Natalia Zabolotnykh ◽  
Mariia Sergeeva ◽  
Ekaterina Romanovskaya-Romanko ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Cellular Immune Response ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Adaptive Immune Response ◽  
Reading Frame ◽  
Vector Vaccine ◽  
Specific Effector ◽  
Cellular Immune

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

scholarly journals Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease

2021 ◽  
Author(s):  
Rebecca H Haberman ◽  
Ramin Herati ◽  
David Simon ◽  
Marie Samanovic ◽  
Rebecca B. Blank ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell Activation ◽  
Cellular Immune Response ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Inflammatory Diseases ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Immune Mediated ◽  
Cellular Immune

Objective: To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

scholarly journals Control and Preventive Study of Brucellosis by Using

2017 ◽  
Vol 3 (6) ◽  
pp. 234
Author(s):  
Rahmahani J ◽  
Handijatno D ◽  
Tyaningsih W ◽  
Suwarno Suwarno
Keyword(s):  
Immune Response ◽  
Sodium Chloride ◽  
Antibody Response ◽  
Brucella Abortus ◽  
Cellular Response ◽  
Booster Vaccination ◽  
Humoral Response ◽  
Igg Antibody ◽  
Whole Cells ◽  
Cellular Immune

The aims of this research is to determine the ability of sub unit lipopolysacharide(LPS) vaccine of Brucella abortus strain S-19 in mice and goat, including IgM and sub classes IgG antibody humoral response, cellular mediated immune response (IL-2, IFN- γ) in mice, also IgG as humoral immunity, IL-4 and IL-12 as cellular immunity, comparison affectivity with Brucella abortus strain RB-51 vaccine in goat . This research has two steps methods. Step first, 30 Balb C mice were divided into 3 groups and vaccinated subcutaneously, First group injectedB. abortus S-19, second group injected LPS and third group injected sodium chloride solution. Booster vaccination was conducted every two weeks till the eight week after first vaccination. The second step performed vaccinated to 30 goats divided into three groups. First group was injected by subcutaneous LPS 50 µg/ml and second group injected LPS 100 µg/ml and the third group injected with sodium chloride as control. Booster vaccination conducted 2 weeks after first vaccination and second vaccination. Result of the research conferred. Result research, antibody response in mice showed vaccination by LPS of B. abortus S-19 showed higher titer than vaccination by whole cells but inverse cellular response. The both vaccines showed induce subclass antibody response, vaccination by LPS tendency to IgM response but vaccination by Whole cells active vaccine tendency to IgG1, IgG 2a and IgG2b. Response antibody in goat on two weeks after first vaccination, vaccination with LPS of B. abortus S-19, dose 50 µg/ml failed or zero titer IgG response but dose 100 µg/ml was 500response antibody on two weeks after second vaccination by dose 50 µg/ml was 340 but by dose 100 µg/ml was 960, while cellular IL-12 response two weeks after first vaccination by dose 50 µg/ml was 22.88 pg/ml but by 100 µg/ml was 62.15 pg/ml. Response cellular IL -12 two weeks after second vaccination 50 µg/ml was 12.04 pg/ml while by dose100 µg/ml was 130.88pg/ml    Cellular immune response IL-4 on two weeks after first vaccination, dose 50 µg/ml showed 55.57 pg/ml but by dose100 µg/ml was 49.35 pg/ ml. Response cellular IL-4 on two weeks after second vaccination by dose 50 µg/ml  was 22.17 pg/ml but by dose 100 µg/ml was 143.89 pg/ml Keyword: Vaccine sub-unit LPS of Brucella abortus S-19, Humoral antibody, Cellular antibody

scholarly journals Antigen Localization Influences the Magnitude and Kinetics of Endogenous Adaptive Immune Response to Recombinant Salmonella Vaccines

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Yanina R. Sevastsyanovich ◽  
David R. Withers ◽  
Claire L. Marriott ◽  
Faye C. Morris ◽  
Timothy J. Wells ◽  
...  
Keyword(s):  
Immune Response ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Cell Culture Supernatant ◽  
Total Serum ◽  
Igg Antibody ◽  
Content Type ◽  
Antigen Localization ◽  
Pet System ◽  
Heterologous Antigens

ABSTRACT The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy for presenting heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ on where heterologous antigens are expressed and localized within the bacterium, and it is unclear how antigen localization modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in cell culture supernatant. In the present study, this Pet system was used to express early secretory antigen 6 (ESAT-6), an immunodominant and diagnostic antigen from Mycobacterium tuberculosis, in Salmonella enterica serovar Typhimurium strain SL3261. Three strains were generated, whereby ESAT-6 was expressed as a cytoplasmic (SL3261/cyto), surface-bound (SL3261/surf), or secreted (SL3261/sec) antigen. Using these RASVs, the relationship between antigen localization and immunogenicity in infected C57BL/6 mice was systematically examined. Using purified antigen and specific tetramers, we showed that mice infected with the SL3261/surf or SL3261/sec strain generated large numbers of Th1 CD4+ ESAT-6+ splenic T cells compared to those of mice infected with SL3261/cyto. While all mice showed ESAT-6-specific antibody responses when infected with SL3261/surf or SL3261/sec, peak total serum IgG antibody titers were reached more rapidly in mice that received SL3261/sec. Thus, how antigen is localized after production within bacteria has a more marked effect on the antibody response than on the CD4+ T cell response, which might influence the chosen strategy to localize recombinant antigen in RASVs.

scholarly journals Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shidan Tosif ◽  
Melanie R. Neeland ◽  
Philip Sutton ◽  
Paul V. Licciardi ◽  
Sohinee Sarkar ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Family Members ◽  
Antibody Responses ◽  
Healthy Controls ◽  
Serological Testing ◽  
Igg Antibody ◽  
Cytokine Responses ◽  
Asymptomatic Infections ◽  
Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

scholarly journals Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes of Brucella abortus in BALB/c Mice

2006 ◽  
Vol 74 (5) ◽  
pp. 2734-2741 ◽  
Author(s):  
Deyan Luo ◽  
Bing Ni ◽  
Peng Li ◽  
Wei Shi ◽  
Songle Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Vaccine ◽  
Brucella Abortus ◽  
Protective Efficacy ◽  
Virulent Strain ◽  
T Helper 1 ◽  
Genetic Vaccine ◽  
Cellular Immune

ABSTRACT This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular immune responses. The specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T-cell proliferative response and induced a large amount of gamma interferon-producing T cells upon restimulation in vitro with recombinant fusion protein L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune response in vivo. This divalent DNA vaccine could also induce a significant level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice. Furthermore, the protection level induced by the divalent DNA vaccine was significantly higher than that induced by the univalent DNA vaccines pcDNA3.1-L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for the first time that the Omp16 gene can be a candidate target for a DNA vaccine against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12 and Omp16 genes can elicit a stronger cellular immune response and better immunoprotection than the relevant univalent vaccines can.

scholarly journals Oral Meloxicam Administration in Sows at Farrowing and Its Effects on Piglet Immunity Transfer and Growth

2021 ◽  
Vol 8 ◽  
Author(s):  
Elena Navarro ◽  
Eva Mainau ◽  
Ricardo de Miguel ◽  
Déborah Temple ◽  
Marina Salas ◽  
...  
Keyword(s):  
Immune Response ◽  
Body Weight ◽  
Weight Gain ◽  
Maternal Behavior ◽  
Interleukin 2 ◽  
Treated Group ◽  
Interleukin 4 ◽  
Control Group ◽  
Piglet Serum ◽  
Cellular Immune

Many factors can lead to an inadequate development of piglets during their first days of life, including poor maternal behavior, which can be due to pain caused by farrowing, and reduced colostrum ingestion. This study investigates the action of meloxicam administered orally at farrowing on piglet weight gain and immunity transfer. Thirty-five multiparous sows were divided into two groups and treated with 0.4 mg/kg of oral meloxicam (oral meloxicam group; n = 18) or with a mock administration (control group; n = 17). A total of 382 piglets were individually weighed on the farrowing day (day 0), as well as on days +9 and +20. Immunoglobulin G (IgG) and A (IgA) concentrations in piglet serum and in sow's saliva, colostrum and milk were measured. Additionally, Interleukin-2 (IL-2), Interleukin-4 (IL-4) and Interferon gamma (IFN-⋎) in serum of piglets and in sow's milk or colostrum were studied. All samples were obtained on days +1, +9, and +20. Piglets from sows in the oral meloxicam group tended to grow faster from day +9 to day +20 than did piglets from control sows (p = 0.059), and this difference was also observed in piglets with low body weight (BW) at birth (p = 0.056). The oral meloxicam group sows tended to increase the colostrum levels of IgA and IgG, as compared with control sows on day +1 (p = 0.068 and p = 0.072, respectively). IgA levels in piglet serum from the oral meloxicam group were significantly higher than in the control group on day +1 and +9 (p = 0.019 and p = 0.011 respectively). Furthermore, IL-2 and IL-4 levels in the serum of piglets from sows in the oral meloxicam group tended to be higher than that in the control group on day +9 (p = 0.078 and 0.056, respectively). The administration of meloxicam orally at the beginning of farrowing in multiparous sows increased immunoglobin and cytokine concentrations in colostrum, improving both humoral and cellular immune response of piglets. Pre-weaning growth of piglets born with a low BW improved in the meloxicam-treated group.

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