Aim and scope:The Iranian Journal of Immunology (I.J.I) is an internationally disseminated peer-reviewed publication and publishes a broad range of experimental and theoretical studies concerned with all aspects of immunology.Types of papers accepted:The Journal will welcome original and review articles on basic and clinical Immunology, Immunogenetics, Transplantation Immunology, Immunohematology, Cancer Immunology, and Allergy. The Journal will also welcome short papers and letters to the Editor.Iranian Journal of Immunology is indexed in the following indexing systems:. MEDLINE. PUBMED. Web of Science (ISI). SCOPUS.

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Index Medicus for Eastern Mediterranean Region (IMEMR)IJI, is an official publication of the Iranian Society for Immunology and Allergy (ISIA), which is published by Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences (SUMS), Shiraz, Iran. AbstractBackground: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB). Objective: To determine the significance of Th2/Th1 ratio and concentration.Background: Patient immune status might be indicative of the variance in bacterial genetics in drug-resistant tuberculous pleuritis and could be used for predicting the risk of multi-drug resistant tuberculous pleuritis (MDR-TB).

Objective: To determine the significance of Th2/Th1 ratio and concentration of PD-L1 in the pleural effusions for prediction of MDR-TB. Methods: We measured the ratio of Th2 to Th1 T cells from pleural effusions in 373 tuberculous pleuritis patients. We also measured the concentration of programmed death ligand-1 (PD-L1) in the pleural effusions of these patients. Afterwards, we determined the optimal cut-off value for predicting the occurrence of multi-drug resistant tuberculous based on the Youden index, diagnostic evaluation test, and receiver operation curve. Multiple logistic analysis was employed to identify the independent risk factors for MDR-TB occurrence. Results: The area under the curve (AUC) of the Th2 to Th1 ratio was 0.66 and the concentration of PD-L1 was 0.71.

Based on the combined detection of PD-L1 concentration in pleural effusion and the Th2 to Th1 ratio, our AUC was 0.81 and had a specificity of 0.92. Only a combined detection was able to identify patients developing multidrug-resistant tuberculosis. Multiple logistic analysis showed that a high concentration of PD-L1 and a high Th2 to Th1 T ratio in pleural effusions were indicative of an immunocompromised status. Therefore, these measurements might be independent risk factors for the occurrence of multidrug-resistant tuberculous.

Conclusion: Evaluation of immune status based on PD-L1 pleural concentration and Th2 to Th1 ratio might predict the risk of MDR-TB occurrence. AbstractBackground: Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths. Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination.Background: Melanoma is a common and malignant cutaneous tumor, which is responsible for a large proportion of skin cancer deaths.

Dendritic cell (DC)-based vaccines have achieved positive results in the treatment of melanoma because of their ability to induce cytotoxic response to facilitate tumor elimination. Objective: To improve the efficacy of dendritic cell-based vaccines by the adjuvant activity of Helicobacter pylori neutrophil activating protein (HP-NAP), which is a virulence factor of Helicobacter pylori, has been proved as a TLR agonist with effective immunomodulatory activity. Methods: The recombinant HP-NAP (rHP-NAP) was expressed by using prokaryotic expression system.

Dendritic cells (DCs) were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After treating with rHP-NAP, the maturation of DCs and dendritic cell-based vaccine were assayed by using flow cytometry and qRT-PCR. The activation and proliferation of T cells were measured by FCM, ELISA and MTT methods. The tumor specific cytotoxic response to resistant B16F10 was detected by using lactate dehydrogenase-release assay and qRT-PCR. Results: The recombinant HP-NAP (rHP-NAP), prepared from E. Coli prokaryotic expression system, was able to significantly promote the maturation of dendritic cell-based vaccine loaded with tumor cell lysate (TCL) of B16F10 (DC-B16F10-TCL). Furthermore, it effectively induced the activation and proliferation of T cells and tumor specific cytotoxic response to resistant B16F10 melanoma tumor cells.

Conclusion: These results suggested that rHP-NAP possesses the potential for use as an adjuvant of dendritic cell-based vaccine in anti-melanoma treatment. AbstractBackground: Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated. Objective: To examine the.Background: Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated. Objective: To examine the effects of pp150 on the maturity and function of murine dendritic cells (DCs). Methods: Maturity status (CD40, CD86, and MHC-II expression) and phagocytic capacity of DCs (dextran uptake assay) were characterized.

Gene expression profiles of ROR-γ, GATA-3, T-bet, and FOXP-3 as well as the protein expression of INF-γ (Th1), IL-4 (Th2), IL-35 (Treg), IL-17A (Th17), IL-22, TNF-α, IL-6, and IL-2 were evaluated in T cells co-cultured with DCs. Results: A significant increase in CD40, CD86, and CCR7 expression and a reduction in the phagocytosis rate were observed in pp150-stimulated DCs compared with unstimulated DCs. T cells co-cultured with stimulated DCs showed higher expressions of ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α. Conclusion: Despite improvements in maturity status, pp150-stimulated DCs does not seem to be able to induce Th1 or Th2 immunity.

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In fact, Th17 and its mediators, IL-17A and IL-22, might be the main inflammatory factors involved in pp150-stimulated DC's action mechanism. However, it is necessary to conduct further investigations to corroborate these observations. AbstractBackground: Emerging evidence suggests that secretome of mesenchymal stem cells has many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of autoimmune and degenerative diseases.

Dipeptidyl Peptidase-IV (DPP-IV)/CD26 and Aminopeptidase N (APN)/CD13.Background: Emerging evidence suggests that secretome of mesenchymal stem cells has many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of autoimmune and degenerative diseases. Dipeptidyl Peptidase-IV (DPP-IV)/CD26 and Aminopeptidase N (APN)/CD13 are ubiquitous ecto-enzymes which can digest various substrates including some chemokines and neuropeptides that are involved in inflammatory conditions. Objective: To evaluate the enzymatic activity of DPP-IV/CD26 and APN/CD13 in MSC conditioned media (MSC-CM). Methods: The MSCs were isolated from the mouse’s abdominal adipose tissues and were cultured without or with preconditioning by adding 2 µg/mL phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). The levels of interleukin-10 (IL-10), nitric oxide (NO), as well as the enzymatic activities of DPP-IV/CD26 and APN/CD13 were measured in MSC-CM.

Results: The level of IL-10 and the enzyme activity of APN/CD13 did not show any changes in the MSC-CM of stimulated and non-stimulated cells. However, NO production was increased after treatment by LPS or PMA; nevertheless, the DPP-IV/CD26 activity was decreased in MSC-CM merely following the stimulation of cells with LPS.

Conclusion: Our results indicated that MSC‐secretome had DPP-IV/CD26 and APN/CD13 activity. The DPP-IV/CD26 activity was decreased following stimulation of MSCs by toll-like receptor 4 agonist. Further studies are needed to reveal the possible contribution of DPP-IV/CD26 and APN/CD13 in the anti-inflammatory functions of MSC-CM. AbstractBackground: Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well.

Objective: To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe.Background: Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well. Objective: To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice. Methods: Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group.

Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA kits. Quantitative RT-PCR was performed to detect the transcript amounts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis. Results: The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0).

Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway. Conclusion: Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response. AbstractBackground: Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol. Objective: To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L.

(TT) on the proteome and expression.Background: Atherosclerosis is a chronic inflammation that interferes with blood arteries functions due to the accumulation of low density lipids and cholesterol. Objective: To investigate the effect of aqueous extract and saponin fraction of Tribulus terrestris L.

(TT) on the proteome and expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the human umbilical vein endothelial cells (HUVEC) and human bone marrow endothelial cell (HBMEC) lines. Methods: Two cell lines were cultured and induced with lipopolysaccharide (LPS). The primed cells were then treated with aqueous extract and saponin fraction of TT. The protein profile of the endothelial cells was assessed under normal and LPS-induced conditions using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 2D gel electrophoresis (2-DE).

The levels of VCAM-1, ICAM-1, and E-selectin were estimated by use of western blotting. Results: LPS-induced HUVECs and HBMECs were shown to significantly increase the expression of ICAM-1, VCAM-1, and E-selectin in comparison to control groups. Our findings revealed that TT extract resulted in significantly more reduced levels of proteom (80 spots) as well as all the three mentioned proteins compared with the effect of saponin fraction alone. Conclusion: TT extract and its saponin fraction exerted anti-inflammatory effects on HUVEC and HBMEC lines and reduced the expression of ICAM-1, VCAM-1, and E-selectin. However, the anti-inflammatory effect of aqueous extract was greater than that of saponin fraction. Therefore, TT could be considered as a potential candidate for the treatment or prevention of atherosclerosis. AbstractBackground: Pseudomonas aeruginosa has an important role in nosocomial infections.

Objective: To evaluate biological activity of the detoxified LPS (D-LPS) entrapped into Poly lactic-co-glycolic acid (PLGA) nanoparticles. Materials: LPS was extracted and detoxified from the P. Aeruginosa strain PAO1.Background: Pseudomonas aeruginosa has an important role in nosocomial infections. Objective: To evaluate biological activity of the detoxified LPS (D-LPS) entrapped into Poly lactic-co-glycolic acid (PLGA) nanoparticles. Materials: LPS was extracted and detoxified from the P. Aeruginosa strain PAO1. The D-LPS, conjugated to the PLGA nanoparticles with 1-ethyl-3-dimethyl aminopropyl carbodiimide (EDAC) and N-hydroxy-succinimide (NHS).

The connection was evaluated by FTIR (Fourier transform infrared), Zetasizer, and Atomic Force Microscope (AFM). The BALB/c mice injected intramuscularly with the D-LPS-PLGA with two-week intervals and then challenged two weeks after the last immunization. The bioactivity of the induced specific antisera and cytokines responses against D-LPS-PLGA antigen was assessed by ELISA. Results: D-LPS-PLGA conjugation was confirmed by FTIR, Zetasizer, and AFM. The ELISA results showed that D-LPS was successful in the stimulation of the humoral immune response. The immune responses raised against the D-LPS-PLGA, significantly decreased bacterial titer in the spleen of the immunized mice after challenge with PAO1 strain in comparison with the control groups. Conclusion: The conjugation of the bacterial LPS to the PLGA nanoparticle increased their functional activity by decrease in bacterial dissemination and increase the killing of opsonized bacteria.

AbstractBackground: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells.Background: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) in plasma was evaluated by ELISA assay.

Results: Increased percentages of CD4+CD25+ T cells, CD4+CD39+ T cells, CD4+Foxp3+ T cells, and CD4+CD25High T cells were observed in children with ALL in comparison to healthy controls. In addition, the ALL patients with 12 months of therapy showed increased CD4+CD39+ T cells compared to the ALL patients with ≤12 months and healthy controls. Similarly, the CD4+CD25+ T cells and CD4+Foxp3+ T cells increased according to maintenance therapy time. Conclusion: Our results showed increased percentages of regulatory T cells in pediatric ALL patients despite chemotherapy, which might be compromising the anti-leukemic cellular immune response. AbstractAsthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines.

Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active.Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active drugs. To solve this paradox, we need objective airway biomarkers to tailor the proper medications to the proper patient. Biomarkers should have one or more of the following characteristics: 1) could differentiate poor symptoms perceivers from over-perceivers, 2) could predict disease activity and hence disease outcome, 3) could clarify asthma phenotype responders from non-responders, and finally 4) could characterize different clinical asthma phenotypes. Therefore, we have conducted a review of literature trying to apply those four parameters to different airway inflammatory biomarkers.

We found that FeNO fulfilled the four proposed clinical parameters of airway inflammatory biomarkers whereas; serum periostin was the single best systemic biomarker of airway luminal and tissue eosinophilia in severe uncontrolled TH2 asthma phenotype. Thus, this may be considered a trial towards tailoring the proper medication to the proper patient. However, application of biomarkers in clinical practice requires easier and cheaper techniques together with standardized methods for sample collection and analysis. AbstractBackground: The immunomagnetic separation technique is the basis of monocyte isolation and further generation of monocyte-derived dendritic cells. Objective: To compare the efficiency of monocyte positive and negative separation, concentration of beads, and their impact on generated dendritic cells.Background: The immunomagnetic separation technique is the basis of monocyte isolation and further generation of monocyte-derived dendritic cells. Objective: To compare the efficiency of monocyte positive and negative separation, concentration of beads, and their impact on generated dendritic cells.

Methods: Monocytes were obtained using monoclonal antibody-coated magnetic beads followed the Ficoll-Paque gradient separation of mononuclear cell fraction from the peripheral blood of 6 healthy volunteers. CD14 expression was analyzed by flow cytometry. Results: The percentage of MDDCs generated from monocytes obtained by positive and negative selection was comparable (51.8 ± 15.0 and 46.7 ± 3.4, respectively; p=0.885). The median values for the number of MDDCs obtained from monocytes after positive selection (3.9 × 106) and for MDDCs obtained from monocytes after negative selection (3.1 × 106) were comparable (p=0.194).

The use of the recommended or half of the amount of beads for both types of separation had no significant influence on the percentage of isolated cells. Conclusions: Both types of magnetic separation including recommended and reduced concentrations of beads did not affect the yield and the purity of monocytes and their surface CD14 expression. However, DCs originated from the “positively” separated monocytes had noticeable higher expression of CD80. AbstractBackground: Helicobacter pylori (H. Pylori), is a common infection in pregnant women accompanied by variations in the levels of the IgM, IgA and IgG antibody isotypes. The variations of anti-H. Pylori antibodies during and after pregnancy, and the extent of protection they provide to the mother and the.Background: Helicobacter pylori (H.

Pylori), is a common infection in pregnant women accompanied by variations in the levels of the IgM, IgA and IgG antibody isotypes. The variations of anti-H. Pylori antibodies during and after pregnancy, and the extent of protection they provide to the mother and the fetus are not completely understood. Objectives: To investigate the changes of the anti-H.

Pylori IgM, IgA and IgG levels in healthy Omani pregnant women during pregnancy and 3 months after delivery. Methods: Serum samples obtained from 70 Omani healthy pregnant women, with no history of autoimmune diseases, were tested for anti-H. Pylori IgM, IgA and IgG in the first trimester of pregnancy and 3 months after delivery. In parallel and as a control group, sera obtained from a group of 70 healthy non-pregnant Omani women were tested. The levels of anti-H. Pylori IgM, IgA and IgG were measured using standard Enzyme Linked Immunosorbent Assays (ELISAs).

Results: Anti-H. Pylori IgA levels were found to be significantly higher during pregnancy (p=0.046) and after delivery (p=0.02) when compared to the control group. Moreover, a significant increase in the levels of anti-H. Pylori IgM, IgA and IgG was detected after delivery (p=0.002) when compared to the levels during pregnancy. Conclusion: Pregnancy is associated with an increase in the levels of anti-H. Pylori IgA antibodies.

In addition, anti-H. Pylori IgM, IgG and IgA antibody levels increase after delivery. AbstractBackground: Acute Myocardial Infarction (AMI) is the leading cause of disability and death in Iran and many other countries. Objective: To investigate the prognostic value of CCL5 and CCL18 in patients with acute myocardial ischemia. Methods: In this cohort study we recruited and followed 50 patients.Background: Acute Myocardial Infarction (AMI) is the leading cause of disability and death in Iran and many other countries. Objective: To investigate the prognostic value of CCL5 and CCL18 in patients with acute myocardial ischemia.

Methods: In this cohort study we recruited and followed 50 patients with acute anterior myocardial infarction (AAMI) for developing cardiovascular accidents in a 6-month period. CCL5 and CCL18 levels were measured on admission, at day 5 and at day 180 posthospitalization. Results: CCL18 and CCL5 levels at day 180 were higher in patients with late (day 180) and early (day 5) LVEF less than 35% compared to those with higher LVEF (p=0.05 and p=0.042, respectively). There was a negative correlation between early and late LVEF and regional wall motion abnormalities (p=0.001 and p=0.002, respectively). There was also a trend of negative correlation between CCL18 levels at day 5 and LVEF levels at day 180 post-hospitalization (p=0.06).

Conclusion: CCL18 has a correlation with cardiac function in patients with AAMI and it might be considered as an indicator of poor LVEF in patients with AAMI. AbstractBackground: Cytokines are cell signaling molecules which upon release by cells facilitate the recruitment of immune-modulatory cells towards the sites of inflammation. Genetic variations in cytokine genes are shown to regulate their production and affect the risk of infectious as well as autoimmune diseases.Background: Cytokines are cell signaling molecules which upon release by cells facilitate the recruitment of immune-modulatory cells towards the sites of inflammation. Genetic variations in cytokine genes are shown to regulate their production and affect the risk of infectious as well as autoimmune diseases.

Intron-3 of interleukin-4 gene (IL-4) harbors 70-bp variable number of tandem repeats (VNTR) that may alter the expression level of IL-4 gene. Objective: To determine the distribution of IL-4 70-bp VNTR polymorphism in seven genetically heterogeneous populations of Chhattisgarh, India and their comparison with the finding of other Indian and world populations. Methods: A total of 371 healthy unrelated individuals from 5 caste and 2 tribal populations were included in the present study. The IL-4 70-bp VNTR genotyping was carried out using PCR and electrophoresis.

Results: Overall, 3 alleles of IL-4 70-bp VNTR (a2, a3 and a4) were detected. The results demonstrated the variability of the IL-4 70-bp VNTR polymorphism in Chhattisgarh populations. Allele a3 was the most common allele at the 70-bp VNTR locus in all populations followed by a2 allele. This study reports the presence four repeat allele a4 at a low frequency in the majority of the Chhattisgarh populations studied. Further, the frequency of the minor allele (a2) in Chhattisgarh populations showed similarity with the frequencies of European populations but not with the East Asian populations where the a2 allele is a major allele. Conclusions: Our study provides a baseline for future research into the role of the IL-4 locus in diseases linked to inflammation in Indian populations.

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