Iranian journal of immunology
Volume:15 Issue: 4, 2018 Autumn

Infection with human papillomavirus type 16 (HPV-16) is known to cause cervical cancer, hence the several HPV therapeutic vaccines are developed in E7 oncoproteins and targeted on cell-mediated immunity. Human dendritic cells (HuDCs) are extensively employed in HPV therapeutic vaccines as the carrier or platform for inducing adaptive immune responses. However, the immunomodulators need to be further investigated for vaccine effects. Gray oyster mushroom (Pleurotus sajor-caju) containing β-glucans is a potent immunomodulator with potential to be used in vaccines. To study the effect of Pleurotus sajor-caju-β-glucan Polysaccharides (PBG) on human T-lymphocytes by use of the HuDCs’ antigen presentation platform for HPV16 vaccine. The HPV16-E7 recombinant proteins were constructed in E. Coli. HuDCs pulsed with E7 peptide were cocultured with the T-lymphocytes treated with and without PBG. The number of Tlymphocytes( CD4; CD8) was detected by flowcytometry, and the viral response of Tlymphocytes was measured via IFN-γ release. The PBG treated group of Tlymphocytes cocultured with the HuDCs pulsed by the HPV16-E7 proteins showed significantly higher numbers of T-lymphocytes and IFN-γ release compared with Tlymphocytes without PBG in vitro. Moreover, a significant improvement in the level of specific IgG neutralizing antibodies to HPV was found in a murine model. Further observed was an increase in the expansion of helper and cytotoxic T-cells and IFN-γ releases in human system. PBG treatment of T-lymphocytes could be a useful option for prophylactic and therapeutic vaccines in cervical cancer.

Lepista sordida (LS) extract has been shown to possess anti-oxidant, anti-aging, and anti-tumor activities. However, the immunostimulatory effect of LS extract has not been elucidated. To characterize the impact of a water extract of LS (WE-LS) on the maturation and function of mouse dendritic cell (DC) in vitro and in vivo. Mouse bone marrow-derived DCs (BMDCs) were generated. Next, DC maturation was determined by flow cytometry, and cytokine production was measured by ELISA after WE-LS treatment. In addition, DC-induced OVA-specific T cell activation was assayed by [3H]-thymidine incorporation assay. Furthermore, the in vivo effects of WE-LS on DC maturation and Th1 responses in the spleens of mice were assessed by flow cytometry. WE-LS treatment up-regulated co-stimulatory (CD40 and CD80) and MHC class II molecules, increased the production of tumor necrosis factor-alpha (TNF-α), IL-6 and IL-12, and enhanced both the proliferation and IFN-γ secretion of allogenic T cells in BMDCs, partially mediated by the TLR2 and TLR4 signaling pathways. Moreover, the in vivo administration of WE-LS to mice enhanced the up-regulation of CD40, CD80 and MHC class II molecules in spleen DCs. WE-LS also increased the generation of T helper type 1 (Th1) cells in vivo. These results suggest that WE-LS might have the potential to promote immunity against infection and cancer or to serve as an adjuvant in vaccines and immunotherapies.

In recent years attention has been paid to develop effective adjuvant systems for DNA vaccines. Co-formulation of a gene delivery vector with an immunostimulator can enhance therapeutic efficiency of DNA vaccine. To investigate the efficacy of chitosan as a nanodelivery system to enhance antitumor effects of human papilloma virus (HPV)-16 DNA vaccine with IL-12 gene for protection against TC-1 tumor using an animal model. The mice were challenged by subcutaneous injection of TC-1 cells and immunized intramuscularly with DNA vaccine thrice at seven-day intervals. One week after the last immunization, mice were sacrificed and antitumor effects were assessed through measuring lymphocyte proliferation, cytotoxicity, cytokines production, and tumor regression. We found that co-formulation and co-administration of chitosan nanoparticles and IL-12 with HPV-16 E7 DNA vaccine induced higher antitumor effects compared with chitosan or IL-12 alone. E7-specific lymphocyte proliferation index and CTL activity were found to be significantly higher in combination group in comparison to single vaccination with either chitosan or IL-12. Co-formulation of chitosan and IL-12 resulted in higher IFN-γ and IL-4, and decreased IL-10 production. Furthermore, combined vaccination highly inhibited the tumor progression compared with chitosan or IL-12 alone. Chitosan nanoparticle is a promising delivery system for DNA vaccine and IL-12 is an effective genetic adjuvant for the induction of strong antitumor immune response.

Although there have been numerous attempts to develop vaccines for Leishmaniasis, no vaccine can be found against Leishmania in routine use for an effective global vaccination. It seems that one of the reasons for the low efficacy of such vaccines is the lack of a suitable adjuvant. To evaluate the effects of chitosan nanoparticles containing whole Leishmania lysate antigen (WLL) and soluble leishmania antigens (SLA), a first generation Leishmania vaccine, on the type of immune response generated in BALB/c in a murine model of leishmaniasis. The optimum coating ratio between the polymer and antigens was determined according to their physico-chemical properties such as particle size and zeta potential. Chitosan nanoparticles were loaded with antigens via ionic gelation method. BALB/c mice were immunized subcutaneously three times with various nanoparticulate and free antigens with 2-week intervals. There was no significant (P > 0.05) difference concerning the footpad thickness of mice immunized with nanoparticulate formulations containing either SLA or WLL during the experiment period; these formulations induced a strong mixed Th1/Th2 type immune response characterized by the production of IFN-γ and IL-4, and high levels of IgG2a IgG1 anti-Leishmania antibody. Nanoparticulate formulations (CHT: SLA and CHT: WLL) are not suitable candidates for preferential induction of a pure Th1-type immune response and immunization against Leishmania infection. However, it might be a good strategy in other infectious diseases where a mixed Th1/Th2 immune response is required.

The frequency of sensitization to respiratory allergens is different in various geographical regions. To determine the level of specific IgE to respiratory allergens in patients with atopy in Ahvaz, Iran. In this retrospective cross-sectional study, the total and specific IgE data were recorded for 408 patients with allergic rhinitis and asthma referred to allergy diagnostic laboratory in Ahvaz from 2014 to 2017. The specific IgE was measured for nine respiratory allergens including Salsola kali, Triticum aestivum, Lolium perenne, Salix caprea, Prosopis juliflora, Dermatophagoides farinae, Aspergillus fumigatus, Alternaria alternata, Blatella germani using the ImmunoCAP system (Thermofisher-Phadia, Uppsala, Sweden) in referred patients. The median (IQR) age of participants was 15.5(27) years. The most common outdoor aeroallergens were Salsola kali (42.9%), Lolium perenne (32.2%), and Salix caprea (28.2%) while Dermatophagoides farina (21.1%) and Blatella germanica (20.6%) were the most dominant indoor sensitizers. Sensitization to at least one allergen was found in 57.4% of the patients. The prevalence of IgE sensitization to all respiratory allergens was higher in males. The prevalence of IgE sensitization to molds including Aspergillus fumigatus and Alternaria alternata significantly decreased with increased age. The pattern of allergen-specific IgE showed that Salsola Kali and Lolium perenne are the most common aeroallergens in allergic patients. This finding demonstrates the high frequency of IgE sensitization to outdoor allergens in the southwest of Iran.

Bacteremia and sepsis are associated with high mortality, increased hospital stays, and associated costs, especially in trauma patients. Sepsis is a fatal immunological disorder and its pathophysiology is still poorly understood. To ascertain the role of T-helper lymphocyte-related inflammatory serum cytokines in trauma patients with blood culture positive with Gram-negative bacteria. Peripheral blood samples (5 ml) were collected from 40 trauma patients on the day of obtaining positive blood culture (i.e., day 0), followed by an appropriate antimicrobial treatment and sample acquisition on day 4 and only once from 40 age-matched healthy controls. Bead-based cytometric analysis was used to quantify extracellular levels of 16 serum cytokines. The cytokine profiles were compared with those in healthy controls and then correlated to clinical outcomes. A total of 40 patients were enrolled during the study period. Of these, 24 patients (60%) were discharged while 16 (40%) had a fatal outcome. Statistically significant elevated levels of serum IL-6, IFN-γ, TNF- α, IL-17A, IL-17F, and IL-4 were observed in septic patients, while lowered IL-13 levels correlated significantly with a favorable outcome. Sepsis following trauma elicits a heightened immune response in the body and provokes the production of a diverse array of cytokines that is both pro-inflammatory and anti-inflammatory. However, the unique cytokine profile of septic trauma patients is still not well understood.

Primary complement deficiencies are rare diseases. To retrospectively evaluate the clinical and laboratory findings and complications of patients to increase awareness of pediatricians about complement deficiencies, which are rarely encountered. In this study, the clinical and immunological characteristics of 21 patients who consulted the Immunology Department of our hospital between 2003 and 2017 and were diagnosed with classical or alternative pathway complement deficiency were obtained from the file records. Ten patients with C1 inhibitor deficiency, four patients with factor I deficiency, three patients with properdin deficiency, two patients with C8 deficiency, one patient with C1q deficiency, and one patient with C4B deficiency were assessed. The mean age of the patients at diagnosis was 11.4±4.7 years, the age of onset of symptoms was 7.9±3.9 years, and the follow-up period was 6.7±3.9 years. Fourteen cases had a similar medical history in the family. All patients with C1q, factor I, properdin, C8, and C4B deficiencies presented with an infection, and vasculitic rash was present in two patients with factor I deficiency. In addition, immune complex glomerulonephritis was present in one patient with factor I deficiency. Meningococcal, Haemophilus influenzae type B, and pneumococcal vaccines were administered and prophylactic antibiotic treatment was initiated in all patients except patients with C1 inhibitor deficiency. Early diagnosis of complement deficiencies can facilitate prevention of life-threatening complications such as severe bacterial infections by considering prophylactic antibiotics and vaccines. In patients with C1 inhibitor deficiency, achieving an acurate early diagnosis will assist in the management and timely treatment of life-threatening attacks such as upper airway obstruction and improve outcomes.

Chronic inflammation is associated with neoplasms and several types of cancer. Therefore, polymorphisms in the inflammation-related genes could modify the cancer susceptibility. To investigate the associations between IL-1RN VNTR and rs419598 polymorphisms in IL-1 receptor antagonist (IL-1ra) and colorectal cancer (CRC) and gastric cancer (GC) in an Iranian population. In this study, 126 cancer cases (91 CRC and 35 GC) and 97 healthy controls were included. Genotyping of IL-1RN VNTR and rs419598 was performed by PCR amplification and PCR-RFLP, respectively. Logistic regression was applied to identify the independent risk factors for colorectal and gastric cancers by computing the odds ratio (OR) and 95% confidence intervals (95% CI). All statistical analyses were performed using the SPSS statistical software. There were significant differences between cancer groups and control group concerning the frequency of A1/A2 genotypes in IL-1RN VNTR polymorphism. The carrier status of IL-1RN* 2 allele was associated with increased risk of CRC (p = 0.0003; OR = 0.02; 95% CI: 0.491-0.85) and GC (p = 0.0006; OR = 0.106; 95% CI: 0.321-0.035). Also, the homozygous ILRN *2/*2 genotype was associated with increased risk of gastric cancer (p = 0.04; OR = 0.133; 95% CI: 0.020-0.908). There was no association between different alleles of rs419598 and CRC and GC. This study demonstrates an association between the carrier status of IL-1RN* 2 and CRC and GC in an Iranian population.