scholarly journals Longitudinal Variations of M. tuberculosis-Induced IFN-γ Responses in HIV-Negative Pregnant Women Exposed to Tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Paulo Ranaivomanana ◽  
Rila Ratovoson ◽  
Crisca Razafimahatratra ◽  
Arimanitra Razafimahefa ◽  
Jonathan Hoffmann ◽  
...  
Keyword(s):  
Immune Responses ◽  
Pregnant Women ◽  
Immune Functions ◽  
Blood Samples ◽  
Healthcare Facilities ◽  
Pulmonary Tb ◽  
Latently Infected ◽  
Ifn Γ ◽  
Lower Magnitude

IntroductionPregnancy triggers an alteration of the immune functions and increases the risk of developing the active tuberculosis (TB) symptoms in exposed women. The effect of pregnancy on the Mycobacterium tuberculosis-specific immune responses used for most of the TB immunodiagnostic assays is not well documented. Here we investigated the changes in the M. tuberculosis-specific IFN-γ production in age-matched pregnant and non-pregnant women according to their TB exposition status.MethodsWe conducted a prospective cohort study on HIV-seronegative pregnant and non-pregnant women with compatible pulmonary TB symptoms addressed to TB healthcare facilities in Antananarivo, Madagascar. Active pulmonary TB was bacteriologically assessed with culture from sputum samples. Clinical data and blood samples were collected at inclusion and after 6 months of follow-up for each individual included. Whole blood samples were stimulated with QuantiFERON TB-Gold Plus (QFT-P) assay antigens. Plasma IFN-γ concentrations were then assessed by ELISA.ResultsA total of 284 women were investigated for the study including 209 pregnant women without confirmed TB (pNTB), 24 pregnant women with bacteriologically confirmed active TB (pATB), 16 non-pregnant women with active TB (ATB), and 35 non-pregnant healthy donors (HC). At inclusion, IFN-γ responses are lower in the pregnant women compared to their age-matched non-pregnant counterparts and independently of their TB status. Among the pregnant women, higher concentrations of M. tuberculosis-specific IFN-γ were observed in those exposed to TB, but with a lower magnitude in the active TB compared to the latently infected pregnant women (p < 0.05 with TB1 and p < 0.01 with TB2). After 6 months of follow-up, the M. tuberculosis-specific IFN-γ responses return to their baseline concentrations except for the pregnant women treated for TB for which none of the QFT-P positive reversed to negative (0%, 0/10) at the end of their TB treatment.ConclusionThese results support the concept of specific immune priorities characterized by a concomitant reduction in inflammatory immunity during pregnancy and corroborate the important role of activating the M. tuberculosis-specific immune responses to control the infection when the pregnant women are exposed to the pathogen.

Boost and Loss Of Immune Responses Against Tumor-Associated Antigens In The Course Of Pregnancy As a Model For Immunotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4505-4505 ◽  
Author(s):  
Mathias Lutz ◽  
Medical Student ◽  
Miriam Alb ◽  
Andrea Worschech ◽  
Sabine Gahn ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Prospective Study ◽  
Pregnant Women ◽  
Longitudinal Analysis ◽  
Peripheral Blood ◽  
Delivery Time ◽  
Cross Sectional ◽  
Ifn Γ ◽  
Time Point

Background The therapeutic potential of allogeneic hematopoietic stem cell transplantation (HSCT) mainly relies on graft-versus-leukemia effects mediated by donor-derived T cells targeting both minor histocompatibility antigens and tumor-associated antigens (TAAs). The efficacy of TAA-mediated immune responses particularly depends on the level of antigen expression in the target tissue and the presence of a proinflammatory immune environment allowing donor-derived T cells to overcome peripheral tolerance and to attack the malignant cells in a selective manner. As several TAAs with clinical relevance in tumor and/or transplant immunotherapy such as Mucin 1 (MUC-1), Preferentially expressed antigen of melanoma (PRAME), Wilms tumor protein 1 (WT1) and Human epidermal growth factor receptor 2 (HER2/neu) are highly expressed in the placental tissue we investigated the effects of pregnancy on the frequency of immune responses against these TAAs in a prospective study. A cross-sectional analysis in a previously reported group of 114 healthy volunteer blood donors revealed no significant effects of prior pregnancies. Here, we present the results of the longitudinal analysis in women during and after their first pregnancy. Materials and Methods After local ethical approval and written informed consent a total of 44 HLA-A*02:01-positive women during their first pregnancy were enrolled in this prospective study. Immune responses against TAAs were assessed at four different time points: First or second trimester (Time point A, n=43), 1 to 3 days after delivery (Time point B, n=31), 6 to 8 weeks after delivery (Time point C, n=34) and after completed nursing (Time point D, n=14). At each time point peripheral blood was drawn and peripheral blood mononuclear cells (PBMCs) were collected by density gradient centrifugation. Isolated CD8+ T cells were stimulated with irradiated T2 cells which were loaded with immunodominant peptides (0.1 and 10 µM) of HER2/neu, MUC-1, PRAME, and WT1. Interferon-gamma (IFN-γ) mRNA expression was measured by quantitative polymerase chain reaction (qPCR) after extraction of total RNA. IFN-γ mRNA expression was calculated as relative fold change compared to the irrelevant melanoma antigen Glycoprotein 100 (gp100). A two-fold change was considered as cut-off for positive results. A HLA-A*02:01 restricted CMV peptide was used as positive control. Results All results are presented in Figure 1. Positive immune responses are presented above the cut-off line. A significant number of positive immune responses against MUC-1, PRAME and WT1 were found during pregnancy (Group A) and early after delivery (Group B). The frequency of positive immune responses against these TAAs decreased during and/or after the period of nursing leaving only one borderline significant finding behind (Group C and D). Against HER2/neu there were none or only single events of immune responses detectable in any group. Conclusions The results from this longitudinal analysis show that immune responses against the transplant-relevant TAAs MUC-1, PRAME and WT1 are detectable in pregnant women but are lost after delivery. These findings are in line with our observations from the inter-individual cross-sectional study where women with prior pregnancy did not have a significantly increased frequency of immune responses against TAAs compared to women without prior pregnancies. The abrogation of the immune response as shown in a longitudinal manner is likely to be a result of an immunosuppressive environment induced by increasing levels of steroid hormones during pregnancy. As immune responses against TAAs can be found also in non-pregnant women we assume that the overexpression of TAAs in the placenta induces a boost in autoimmune responses that is consequently compromised by the immunosuppressive environment. Therefore pregnancy may be a useful model for the boost and the regulation of immune responses against TAAs with implications for immunotherapy. Disclosures: No relevant conflicts of interest to declare.

Immunomodulatory effects of dehydroepiandrosterone in proestrus female mice after trauma-hemorrhage

2003 ◽  
Vol 95 (2) ◽  
pp. 529-535 ◽  
Author(s):  
Markus W. Knöferl ◽  
Martin K. Angele ◽  
Robert A. Catania ◽  
Michael D. Diodato ◽  
Kirby I. Bland ◽  
...  
Keyword(s):  
Immune Responses ◽  
Sham Operation ◽  
Splenocyte Proliferation ◽  
Immune Functions ◽  
Shed Blood ◽  
Adrenal Steroid ◽  
Ifn Γ ◽  
Tissue Trauma ◽  
Cellular Immune ◽  
Anti Inflammatory Cytokine

Studies indicate that administration of the adrenal steroid dehydroepiandrosterone (DHEA) after trauma-hemorrhage in male mice improved cellular immune functions and reduced mortality rates from subsequent sepsis. There is evidence, however, that DHEA is converted to estrogens in males and that estrogens are immunoprotective after trauma-hemorrhage (TH). In contrast, DHEA in females can be converted to testosterone that has deleterious effects on immune functions. The aim of our study, therefore, was to determine whether administration of DHEA in proestrus females after TH would deteriorate immune responses. Proestrus female C3H/HeN mice (age 7–8 wk) were subjected to laparotomy (i.e., soft tissue trauma induced) and hemorrhagic shock (35 ± 5 mmHg for 90 min) or sham operation. The mice then received DHEA (100 μ/25 g body wt) or vehicle subcutaneously followed by fluid resuscitation (4× the shed blood volume). Plasma IL-6, splenocyte proliferation, splenocyte IL-2, IL-3, IFN-γ, IL-10 release, and splenic Mφ IL-1β, IL-6, IL-10, and IL-12 release were determined 24 h after TH. Plasma IL-6 levels were significantly increased in vehicle-treated females, and DHEA administration markedly attenuated this response. In vehicle-treated females, splenocyte proliferation, IL-2, IL-3, and IFN-γ release, and splenic Mφ IL-1β, IL-6, and IL-12 release were maintained or slightly enhanced after TH. In DHEA-treated females, however, these immune functional parameters were either unaltered compared with vehicle-treated animals or even further enhanced, but surprisingly were not depressed. Moreover, DHEA reduced splenocyte and splenic Mφ anti-inflammatory cytokine (i.e., IL-10) production after TH compared with vehicle-treated females. Because DHEA further enhances the immune responsiveness in proestrus females after TH, this hormone might be a useful adjunct even in females for further enhancing immune responses and decreasing the mortality rate after trauma and severe blood loss.

scholarly journals T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

2002 ◽  
Vol 9 (2) ◽  
pp. 251-256 ◽  
Author(s):  
Alda Maria Da-Cruz ◽  
Rita Bittar ◽  
Marise Mattos ◽  
Manuel P. Oliveira-Neto ◽  
Ricardo Nogueira ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Subsets ◽  
Mucosal Leishmaniasis ◽  
Long Term Follow Up ◽  
Ifn Γ ◽  
Active Disease

ABSTRACT T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations.

scholarly journals Dysregulated immunity in SARS-CoV-2 infected pregnant women

2020 ◽  
Author(s):  
Morgan L. Sherer ◽  
Jun Lei ◽  
Patrick Creisher ◽  
Minyoung Jang ◽  
Ramya Reddy ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cord Blood ◽  
Pregnant Women ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Expression ◽  
Johns Hopkins Hospital ◽  
Blood Samples ◽  
Placental Inflammation ◽  
The Impact

AbstractImportanceThe effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated.ObjectiveTo assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women.DesignImmune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood.SettingJohns Hopkins Hospital (JHH)ParticipantsPregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study.ExposuresSARS-CoV-2Main Outcomes and MeasuresParticipant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression.ResultsSARS-COV-2 positive pregnant women expressed more IL1β, but not IL6, in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy.Conclusions and RelevanceSARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

scholarly journals INTERFERON GAMMA AND INTERLEUKIN-10 LEVELS IN PBMC OF ACTIVE AND LATENT TUBERCULOSIS PATIENTS AS WELL AS HEALTHY INDIVIDUALS

2018 ◽  
Vol 24 (2) ◽  
pp. 122
Author(s):  
I G.A. Wiradari Tedja ◽  
Jusak Nugraha1 ◽  
Betty Agustina Tambunan ◽  
Fransisca Sri Oetami
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Interleukin 10 ◽  
Healthy People ◽  
Pulmonary Tb ◽  
Latent Tb ◽  
Ifn Γ ◽  
The Mean ◽  
Fusion Antigen

Tuberculosis (TB), an infectious disease caused by a Mycobacterium tuberculosis, is still a health problem in Indonesia, and the world. One of the failures to control the TB epidemic is due to the lack of effective vaccines available today. Protective immune responses to M.tuberculosis are dominated by cellular immunity and less by humoral immunity. IFN-γ, and IL-10 play a role in the protection of against M.tuberculosis, and the pathogenesis of TB. Fusion antigen ESAT-6-CFP-10 has a strong antigenicity to T cells and stimulates specific cellular immune responses, thereby providing benefit in immune responses that are protective against M.tuberculosis infection. The aimed of this study was to know the difference betwen IFN-γ, and IL-10 levels on PBMC culture of active TB, latent TB, and healthy people after ESAT-6-CFP-10 fusion antigen stimulation. This study used an in vitro of quasi experimental design in PBMC cultures of active TB, latent TB, and healthy people groups stimulated by ESAT-6-CFP-10 antigen fusion Mycobacterium tuberculosis. IFN-γ, and IL-10 levels were measured by ELISA method. The results were analyzed by one-way ANOVA. The mean levels of IFN-γ post-stimulation of ESAT-6-CFP-10 fusion antigens did not differ (p=0.359) in the active pulmonary TB group (0.07 - 2114), latent TB (6.84 - 1381) and healthy people 1.88 - 1807.70), as well as the mean levels of IL-10 (p=0.712) in the active pulmonary TB (16.70 - 328.80), latent TB (29.70 - 323.60 ) and healthy people (31.30 - 958). There were no significant differences in levels of IFN-γ and IL-10 in active TB, latent TB, and healthy people after stimulation by fusion antigen ESAT-6-CFP-10. 

Evolution of SARS-CoV-2 immune responses in nursing home residents following full dose of the Comirnaty COVID-19 vaccine

2021 ◽  
Author(s):  
Estela Gimenez ◽  
Juan Alberola ◽  
Ignacio Torres ◽  
Eliseo Albert ◽  
Maria Jesus Alcaraz ◽  
...  
Keyword(s):  
T Cells ◽  
Nursing Home ◽  
T Cell ◽  
Immune Responses ◽  
Nursing Home Residents ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Ifn Γ

Objectives: There is scarce information as to the durability of immune responses elicited by the Comirnaty COVID-19 vaccine in nursing home residents. Here, we assessed SARS-CoV-2-Spike (S)-targeted antibody and functional T cell responses at around 6 months after complete vaccination. Methods: The sample comprised 46 residents (34 females; age, 60-100 years), of whom 10 had COVID-19 prior to vaccination. Baseline (median of 17.5 days after vaccination) and follow-up (median, 195 days) plasma specimens were available for quantitation of SARS-CoV-2-S antibodies and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry. Results: In total, 44/45 participants had detectable SARS-CoV-2-S antibodies at follow-up. Overall, antibody levels were found to decrease (median, 4.8 fold). Antibodies waning was more frequent (P<0.001) in SARS-CoV-2 naive (29/35) than in recovered (1/10) residents. SARS-CoV-2-S IFN-γ CD8+ T cells were detected in 33/46 and 24/46 at baseline and follow-up, respectively. The figures for CD4+ T cell counterparts were 12/46 and 30/46. Detectable SARS-CoV-2 IFN-γ CD8+ and CD4+ T cell responses at follow-up were more common in recovered (8/10 and 7/10, respectively) than in naive residents (9/36 and 25/36, respectively). For those with detectable responses at both time points, SARS-CoV-2-S IFN-γ CD8+ T cell frequencies decreased significantly (P=0.001) over time whereas the opposite (P=0.01) was observed in CD4+ T cells. Conclusion: Almost all residents displayed detectable SARS-CoV-2-S-reactive antibodies and T cell responses, respectively, by around 6 months after complete vaccination with Comirnaty COVID-19 vaccine, albeit generally waning in magnitude over time. Keywords: SARS-CoV-2, Comirnaty COVID-19 vaccine, SARS-CoV-2-S antibodies; SARS-CoV-2-S T cells, Nursing home residents.

Isolation of Stenotrophomonas maltophilia from Clinical Samples in Some Hospitals in Shiraz, Iran

2020 ◽  
pp. 1-3
Author(s):  
Majid Baserisalehi ◽  
Samira Zarezadeh ◽  
Majid Baserisalehi ◽  
Saeed Shoa
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Enterobacter Aerogenes ◽  
Late Summer ◽  
Early Spring ◽  
Clinical Samples ◽  
Bacillus Species ◽  
Microbiological Analysis ◽  
Blood Samples ◽  
Healthcare Facilities ◽  
Phenotypic Methods

Stenotrophomonas maltophilia is an emerging pathogenic non-fermentative Gram-negative Bacillus species. It has caused many nosocomial infections and can be isolated from various hospital wards and healthcare facilities. Research has shown that most of its strains are inherently resistant to many antibiotics and have multidrug resistance. This research intended to determine its occurrence frequency at some Hospitals in shiraz, Iran. The present study was conducted in six months (from early spring to late summer 2019). Clinical samples (Blood, Urine and cerebrospinal fluid (CSF)) collected from 120 patients afflicted with various infections. The samples were transferred to the Laboratory and subjected to microbiological analysis. Identification of the isolates was carried out by phenotypic methods and Stenotrophomonas maltophilia isolates verified using molecular methods. In total, various bacteria were isolated from 84 clinical samples. The isolates were Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Stenotrophomonas maltophilia, Staphylococcus aureus and Pseudomonas aeruginosa. Stenotrophomonas maltophilia was isolated from 17 (20.2%) positive samples and most of them were isolated from blood samples. Our finding indicated that Stenotrophomonas maltophilia isolated more from blood samples follow by CSF sample. In addition, our finding illustrated that Stenotrophomonas maltophilia can be considered as the common nosocomial agent at hospitals in Shiraz, Iran.

Awareness of Pregnant Women for COVID-19 Infection

2020 ◽  
Author(s):  
Erhan Okuyan ◽  
Emre Gunakan ◽  
Sertaç Esin
Keyword(s):  
Pregnant Women ◽  
Respiratory Diseases ◽  
Prospective Observational Study ◽  
Information Source ◽  
Home Birth ◽  
Patient Characteristics ◽  
Emotional Status ◽  
Prevention Method ◽  
And Behavior

Covid outbreak has been getting worse and spread affected all over the world. Pregnant patients are also vulnerable to respiratory diseases. We aimed to evaluate the awareness, emotional status, and behavior of pregnant during the COVID outbreak. This study's main benefit is to analyze the knowledge and understanding of pregnant women about the pandemic and draw attention to the prevention issues that need improvement. This research is a prospective observational study that 199 patients subjected to a questionnaire including 29 questions about patient characteristics, pregnancy information, knowledge about COVID19-infection, behavioral and emotional changes. 130 (65.3) of the patients stated an above-average knowledge level. Television was the most frequent information source (75.4%, n:150) and was the only information source for 90 (45.1%) of the patients. Sixty-nine patients used more than one information source. More than one prevention method uses by 149 (75%) of the patients. Washing hands (n:183, 92.0%) and cleaning the house (n:122, 61.3%) were the most preferred methods. Only 55 (27.6%) of the patients used a mask for prevention. 88(44.2%) of the patients stated that they preferred a shorter hospital stay, and 75 (37.7%) of the patients indicated that they postponed or avoided the pregnancy follow-up visits due to the COVID-19 issue. Pregnant women seem to be aware and stressed of COVID-19, but knowledge of what to do seems insufficient. Patients informed of risks of COVID infection, unplanned hospital admission, and chances of avoiding necessary visits and home birth demands.

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