MTORC1-Independent IgA Production: A Unique Pathway for Gut Immune Homeostasis.

Although Ayurved medicines have 3000 years long history of traditional use for the treatment of diseases, scientific evidences in support of the therapeutic effect and safety of most of the preparations yet to be explored and justified. The present study aimed to evaluation of the immunostimulating activity of five preparations of Ayurved medicines namely Kanakasav, Dasamularista, Draksharista, Saribadi and Bramhi Rasayan manufactured and marketed in Bangladesh. Freshly prepared Balb/c mice splenocytes were treated with 1, 5 and 10% (v/v) of different Ayurved preparations and the cells were sub-cultured at 37ºC, humidified atmosphere containing 5% CO2 for 120 hours. The production of IgM and IgG antibodies, and proliferation of cells were determined by enzyme-linked immunosorbent assay (ELISA), and 3-(4,5-dimethylthiazol-2-y)-2,5-diphenylterazolium bromide (MTT) methods, respectively. Among the five preparations tested, Kanakasava and Saribadi stimulated the proliferation of splenocytes and enhanced production of both IgM and IgG antibodies. Interestingly, KNK at the dose of 1% exerted immunostimulating activities but the higher doses 5% and 10% did not show any stimulating activities, rather those concentrations of KNK were found to be toxic to the spleen cells. Similarly, 1% concentration of SDI stimulated the splenocytes proliferation and IgM and IgG antibodies productions. Higher doses resulted with the decreased production of IgM and IgG antibodies by the 5% and 10% concentrations of SDI because of the similar reason as illustrated for KNK. This result is also an indicator of narrow safety profile of both of these Ayurved medicines, KNK and SDI. The other three Ayurved preprations - Dasamularista, Draksharista and Bramhi Rasayan failed to induce immunostimulation in vitro. Although Bramhi Rasayan (BRS) showed stimulating activity at the dose of 10% (v/v), it could not induce the production of antibody. This is the first report on the evaluation of immunostimulating activities of Kanakasav, Dasamularista, Draksharista, Saribadi and Bramhi Rasayan which resulted the preliminary immunostimulating activities of Kanakasav and Saribadi. Further investigations are required with the comprehensive experimental studies to explore its immunostimulating potential and safety of the two preparations.

Background: The relationship between SARS-CoV-2-carrying time and specific antibody production has not yet been reported in re-admitted COVID-19 patients. We reported a case of mild COVID-19 with long virus-carrying time, weak production of virus-specific IgG and IgM antibodies, and recurrence of positive SARS-CoV-2 RNA in stool specimens after discharge.Case Presentation: A 27-year-old male was diagnosed as COVID-19 after returning to Meizhou from Wuhan. Despite extremely mild symptoms, the patient was hospitalized for 24 days because of persistent positive SARS-CoV-2 RNA detection. Three days after recovery discharge, he was hospitalized again for 7 days due to a recurrence of the positive SARS-CoV-2 RNA result, while in a good physical condition. Serological assay, using a fluorescent immunochromatography detection kit specific to SARS-CoV-2, showed that SARS-CoV-2-specific IgM antibodies were undetectable and IgG antibodies were very low on day 8 after onset; both of the antibodies seemingly reached top concentrations on day 15 (just a 6-fold increase of the IgG titer), and then decreased, remaining relatively stable from day 25 after onset until discharge. The production of the IgM and IgG targeting SARS-CoV-2 in this very mild case was much lower than that in a severe case of COVID-19 during the same hospitalizing period, and the latter was used as a control.Conclusion: Mild COVID-19 patients could carry SARS-CoV-2 for a long time, which may be related to the weak production of the virus-specific IgG and IgM. Recurrence of positive SARS-CoV-2 RNA could occur in mild COVID-19 possibly due to intermittent virus shedding, so strict quarantine and health surveillance should be taken for all discharged COVID-19 patients to prevent a potential virus spread.

Immunostimulants are greatly required for the upregulation of immunity to fight against viral and bacterial infections and cancers. Bell peppers (Capsicum annuum L.), eaten as vegetables, are rich sources of vitamin C and E, provitamin A, β-carotene, and numerous phenolic compounds. Antimicrobial, antioxidant, anti-mutagenic and anti-inflammatory properties of Bell peppers were reported. Our research group for the first time reported the immunomodulatory activities of Bell peppers. In this study, we evaluated the antibody production abilities of two different colored Bell peppers (red and green) in the culture of antibody producing splenic B cells of mice. Antibodies and the number of viable cells were determined by an ELISA and MTT assays, respectively. Red Bell pepper Extract (RBPE) at the doses of (0.375, 0.75, 1.5, and 2.25 mg/mL) significantly augmented the production of polyclonal IgM and IgG antibodies in-vitro. The highest amount of IgM antibody production was observed by the dose of 1.5 mg/kg which was 3 times higher than that of the untreated cells. Similarly, RBPE also enhanced the production of IgG antibody in the culture of murine splenic B cells. On the contrary, cultural treatment of murine splenic B cells with Green Bell pepper Extract (GBPE) could not stimulate the B cells, and hence, failed to produce neither IgM nor IgG antibody. Thus the current findings suggest that consumption of Red Bell Pepper extract or its vegetables, not green pepper, may be beneficial to strengthen humoral immune responses. Bangladesh Pharmaceutical Journal 24(1): 45-53, 2021

Female preponderance in many diseases suggested with autoimmune pathogenesis, multiple sclerosis (MS) being classified as one of them, indicates a role for hormonal factors such as estrogen in disease development. To bypass monthly hormonal fluctuations in females, we evaluated in male patients with MS and male blood donors the effect of 17-beta-estradiol on numbers of IgG, IgA and IgM producing cells in cultures of peripheral blood lymphocytes. While estradiol alone had no effect, estradiol in combination with poke-weed mitogen (PWM) yielded in both groups higher numbers of IgG and IgA producing cells when compared with numbers obtained by PWM stimulation alone, indicating an additory effect of estradiol to that of PWM on B cell maturation. This effect was less pronounced in MS than in blood donors, especially for IgG producing cells, probably reflecting higher B cell activation in vivo taking place in MS. On the contrary, cells producing IgG, IgA and IgM antibodies against myelin, myelin basic protein and measles virus were not detectable after stimulation with PWM, nor with PWM and estradiol. Estradiol can in many patients with MS and in blood donors be considered a potent co-activator of B cells in presence of B cell stimulating factor in the form of PWM.

Role of TLR2/MyD88 in the production of specific IgM and IgG antibodies during the immunization of mice against Neospora caninum

No correlation between symptom duration and intrathecal production of IgM and/or IgG antibodies in Lyme neuroborreliosis – a retrospective cohort study in Denmark

Background: Salmonella typhi infection decreases of the immune system and influences the adaptive antibodies among malnourished children. The gonad of Diadema setosum (D. setosum) is one of food sources from marine biota that contains high-quality nutrients and potentially can be used as a dietary supplement for typhoid fever condition.Objective: This study aimed to determine the effect of gonad D. setosum extract on the production of antibody IgM and IgG in an animal model.Method: This experimental study was used BALB/c mice before and after infected Salmonella typhi through intraperitoneally at 0.2 mL x the unit 103 CFU/mL. The level of IgM and IgG production was measured by Enzyme Linked Immune Sorbent Assay (ELISA). Experimental animals were divided into 2 groups. The control group was only fed with standard diets, while at the intervention group received the extract of D. setosum gonad in two doses (100 and 200 mg/kg body weight).Results: Production of IgM antibodies in the control group significantly increased twofold (p=0.001) whereas the intervention group received the extracts of D. setosum gonad (200 mg/kg body weight) could suppress the increase in IgM antibody production and indicate the highest increase of IgG antibody significantly (p<0.05) at day 7.Conclusion: The gonad of Diadema setosum extracts (200 mg/kg body weight) could suppress the increase in IgM antibody productions and indicate the highest increase of IgG antibody titers in mice infected with Salmonella typhi. The role of anti-microbial substances of the gonad of Diadema setosum, is potential to be utilized as dietary supplement to increase body immune system among patients infected by Salmonella typhi.

Immune Mechanisms in Periodontitis: Total and Antigen-Specific IgG and IgA Subclass Antibody-Producing Cells at the Disease Site

Intrathecal synthesis of interleukin-2 and soluble IL-2 receptor in asymptomatic HIV-1 seropositive individuals: Correlation with local production of specific IgM and IgG antibodies

Enhancing and suppressing effects of microbial adjuvants were studied in female mice of the C3H/He, AKR and SL strains. Propionibacterium acnes, Bordetella pertussis, BCG and yeast cell wall (YCW) were chosen as adjuvants. As antigens, we chose hamster erythrocytes (HRBC) which proved to be a weak antigen for mice. Adjuvants were given on day --7, day 0 or day 3, and HRBC were injected on day 0. The results were as follows. 1) P. acnes facilitated IgM and IgG antibody production in AKR mice and suppressed IgM antibody production in SL mice, when given on day --7. When P. acnes was given on day 0, they suppressed IgM antibody production in all of the strains used. 2) When B. pertussis was given on day 0, it exhibited enhancing effects on IgG antibody production in all of the strains and a suppressing effect on IgM antibody production in SL mice. 3) BCG suppressed IgM antibody production in all strains when given on day 0. 4) YCW showed no influence on antibody production in any combination used in this work. 5) SL mice were very sensitive to suppressing effects by adjuvants. Strain differences in the expression of enhancing and suppressing effects by adjuvants appear to be under some control independent of antigen-specific immune response genes.

During refrigerated storage leukocytes in donor blood progressively undergo apoptosis followed by secondary necrosis. Using an inbred rodent transfusion model, recipient animals received viable, necrotic, or apoptotic cells. While transfusion of viable blood MNCs stimulated production of IgM, IgG1 (Th2 type) and IgG2a (Th1-type) antidonor antibodies, leading to a suppression of subsequent DTH to donor antigens, transfusion of apoptotic donor cells led to neither alloimmunization nor immunosuppression. On the other hand transfusion of lysed donor cells resulted in production of IgM and IgG1 (Th2-type) antidonor antibodies and to a strong suppression of subsequent DTH to donor antigens. Intravenously administered spleen cells that had been depleted of professional APCs and enriched for B cells stimulated IgM antidonor antibodies but not IgG antibodies. Transfusion of such cells also led to suppression of subsequent DTH to donor antigens, probably through induction of anergy or apoptosis in alloantigen-reactive recipient cells. Depending on the duration of blood storage any or all of these 4 classes of cells may be present and Th2 and/or Th1 effector mechanisms can be generated following blood transfusion.

DNA methylation modulates allograft survival and acute rejection after renal transplantation by regulating the mTOR pathway

Blood group compatibility is essential for the success of organ transplantation and for reducing the risk of rejection. Studying the optimal conditions for the interaction between blood group-specific monoclonal antibodies and erythrocytes plays a crucial role in accurate blood typing for cell and organ transplantation. Aim. This study aimed to evaluate the agglutination and adsorption activities of blood group-specific IgM and IgG antibodies under varying pH and temperature conditions. Materials and methods. The agglutinating and adsorbing properties of monoclonal antibodies of IgM and IgG isotypes with different isoelectric points were analyzed after incubation with red blood cells (RBCs) under various pH values (6.0, 7.4, 7.8) and temperatures (4 °C and 37 °C). Washed group A red blood cells (RBCs) from healthy volunteers (n = 99) were incubated with a panel of IgM and IgG monoclonal antibodies, including 2-8, 2-10, 2-19 (acid-type anti-A Mabs), 2-23 (alkaline-type anti-A Mabs), and anti-H BRIC-231. Agglutination strength was evaluated microscopically and graded on a scale from 0 to 4. Adsorption activity was assessed by analyzing residual antibody activity in the supernatant after incubation. Results. For IgM of alkaline type and IgG3 antibodies, with optimal adsorbing activity in alkaline medium at 4 °C, maximal adsorbing activity at 37 °C was detected in acid medium. IgM Mabs exhibited stronger agglutination at 4 °C compared to IgG3 Mabs. Polyclonal antibodies, conventional IgM, and acid-type IgM Mabs demonstrated higher agglutination at pH 7.8, in contrast to alkaline-type IgM and IgG3 Mabs. The optimal temperature for maximal adsorption activity corresponded to the temperature that yielded the strongest agglutination. However, the optimal pH for adsorption was generally opposite to that for agglutination. Specifically, at 4 °C, the highest adsorption of conventional and acid-type IgM antibodies occurred at pH 6.0, while at 37 °C, it was observed at pH 7.8. For alkaline-type IgM and IgG3 antibodies, optimal adsorbing activity occurred in alkaline medium at 4 °C, whereas at 37 °C, maximal adsorbing activity was observed in acidic medium. Conclusion. The agglutination and adsorption properties of blood group-specific IgM and IgG antibodies are influenced by both pH and temperature, with their optimal pH values differing for these two functions. For the detection of weak A and B antigen variants via adsorption assays at 4 °C, pH 6.0 is recommended for IgM antibodies, while pH 7.8 is preferable for IgG antibodies.

In the present study, an enzyme-linked immunosorbent assay (ELISA) standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses) and IgE antibodies in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA)=1.17) and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49) and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46) and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12) and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85) and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60) and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.

Upon SARS CoV-2 infection, humoral immune system triggers production of anti-SARS CoV-2 IgM and IgG antibodies. Currently, antibodies against SARS CoV-2 spike protein receptor binding domain play a central role in disease protection, making them potential target for in vitro diagnostics applications. This study determines the expression level and sustainability of anti-receptor binding domain (RBD) SARS CoV-2 IgG in post COVID-19 patients. Anti-RBD SARS CoV-2 IgG antibodies in patient serum were analysed by standardised indirect ELISA using SARS CoV-2 spike receptor binding domain protein and HRP conjugated anti-human IgG antibody (anti-h IgG). The study was conducted using 35 adult patient samples with confirmed SARS CoV-2 infection. Additionally, correlation between antibody response after each stage and disease symptoms in post COVID-19 patients were studied. Maximum antibody titre was seen at Day 40 and decreased relatively to Day 180 in antibody positive samples when compared with controls. Overall, more IgG antibody expression is observed in patients who suffered from loss of smell and taste at Day 40. 71% of the positive subjects in this study showed high SARS CoV-2 IgG antibody concentration of above 10 ng/mL and 37% showed strong antibody concentration above 20 ng/mL at the peak of seroconversion.