Iranian journal of immunology
Volume:3 Issue: 3, Summer 2006

Bacterial DNA has immunostimulatory effects on different types of immune cells such as dendritic cells (DCs). Application of DCs as a cellular adjuvant represents a promising approach in the immunotherapy of infectious disease and cancers. To investigate the effect of tumor antigen pulsed DCs in the presence of CpG-1826 in treatment of a murine model of cancer. WEHI-164 cells (Balb/c derived fibrosarcoma cell line) were injected subcutaneously in the right flank of mice. Bone marrow cells were cultured in the presence of GM-CSF and IL- 4. After 5 days, tumor lysate, CpG-1826, and oligodeoxynucleosides, as control, were added to the culture media and incubated for 2 days. Cytokine production in DCs culture media was measured by ELISA. Then DCs were injected subcutaneously around the tumor site in the right flank of mice. Tumor growth rate was monitored in case and control groups. Two weeks after DCs immunotherapy, cytotoxic assay was conducted using various amounts of effector (splenic T cells) and target cells (WEHI-164 or CT26) for 6 h. Immunotherapy with DCs treated withCpG led to a significant increase in the activity of cytotoxic T cells and decreased tumor growth in immunized mice. In the control group which received DCs without CpG treatment, no change in cytotoxic activity and tumor growth rate was detected. The current study suggests that specific anti tumor immune responses can be induced by DCs matured with CpG and proposes CpG usage in DCs targeted clinical strategies.

HLA genes are highly polymorphic and certain alleles are frequent only in specific populations. Therefore, HLA is a unique tool for studying the genetic relation between different populations. Iranians are ethnically diverse people and one of the major ethnic groups in Iran is Lur population inhabiting along the central and southern parts of Zagros Chain Mountain. Genetic relation among three Lur subpopulations was investigated based on HLA class II profiles. HLA typing was performed using PCR/RFLP and PCR/SSP methods in 154 individuals from three Lur tribes living in Luristan, Kohkiloyeh and Boyerahmad, and Chahar- Mahal and Bakhtiari. The most common DRB1 allele in Lurs of Luristan andKohkiloyeh and Boyerahmad was *1103=4 while DRB1*0701 was the most common allele in Bakhtiari Lurs of Chahar-Mahal and Bakhtiari. DQA1*0501 and DQB1*0301 were the most frequent alleles and DRB1*1103=4-DQA1*0501- DQB1*0301 was the predominant haplotype in the three studied subpopulations. Neighbor-joining tree based on Nei''s genetic distances and correspondence analysis according to DRB1, DQA1, and DQB1 allele frequencies showed a close genetic relation between Lurs of Luristan and Lurs of Kohkiloye and Boyerahmad and they were well separated from Bakhtiaris. The results of AMOVA revealed no significant difference between the three studied groups of Lurs and other major ethnic groups of Iran. The results of this study revealed that Bakhtiaris were geneticallyfar from two other Lur subpopulations. Despite a probable common ancestor, this genetic difference might be explained by Bakhtiaris admixture with other Zagros inhabitants due to their nomadic life style.

Different methods have been used for BCG vaccination. Alginate microspheres are useful in delivery of vaccines to the gastrointestinal tract by oral route. To compare the immune response following oral microencapsulated and subcutaneous (SC) route administration of BCG vaccine in BALB/c mice. Alginate microspheres were produced by an internal emulsification method within olive oil. Four groups of mice were studied, including two groups receiving oral gavages of microencapsulated and free BCG, one receiving SC injection of BCG, and a control group. T cell proliferation, specific anti-BCG total IgG, and IgG subclasses (IgG1 andIgG2a) were compared between groups 5 and 12 weeks after vaccination. Thebest result was achieved using oral microencapsulated form in comparison with oral BCG alone. Delivery of oral BCG with alginate microspheres is an effective way to induce immune response in BALB/c mice.

Polysaccharides have long been used as immune-modulators in variouspathologic conditions including inflammation and solid malignancies. Toevaluate the effects of Zymosan and Betaglucan on cytotoxic reactions in an effectortarget conjugate system. Blood was obtained from 20 healthy subjects; purified mononuclear leukocytes (monocytes and lymphocytes) were extracted and cultured as effector cells by a cytotoxic method. Both adherent and non-adherent cells interacted with the K562 myeloid cell line. The effector-target (E:T) ratio was 1:1, 1:10, and 1:20. To evaluate stimulatory effects of Betaglucan and Zymosan on cytotoxic reactions, samples were divided into case and control groups based on the presence or absence of Betaglucan and Zymosan. MTT assay and sFas ligand (sFasL) concentrations were used to assess the increased killing capacity of effector cells. Our results revealed that Zymosan and Betaglucan can induce cytotoxic responses in macrophages and lymphocytes (P<0.05). The best result was achieved with E:T ratio of 1:1. Both macrophages and lymphocytes produced sFasL following stimulation by Zymosan and Betaglucan, however, the level of production was not statistically significant (P>0.05). Zymosan and Betaglucan can be used as enhancers of the killing capacity of the immune cells; therefore, Betaglucan and Zymosan can be applied as systemic stimulators of the immune response in inflammation and chronic infection.

Recent studies have provided evidence that integrins play roles in recognition of mechanical stimuli and its translation into a cellular response. Integrin signaling may be regulated by a number of mechanisms including accessory proteins such as CD98 (4F2 antigen). To determine CD98 expression by human articular chondrocytes and its involvement in human articular mechanotransduction. CD98 expression was assessed by immunostaining of cryostat sections of snap frozen articular cartilage and in cultured cells by western blotting. Chondrocytesenzymatically isolated from macroscopically normal and osteoarthritic (OA) articular cartilage were grown in short term, primary monolayer culture and used in a resting state or following mechanical stimulation at 0.33Hz. Human articular chondrocytes express CD98 and immunoreactivity revealed a similar heterogeneous pattern of CD98 in both normal and osteoarthritic (OA) human articular cartilage. No role of CD98 was detected by electrophysiological study. It appears that CD98 is expressed in a similar pattern in both normal and osteoarthritic (OA) cartilage.Although we detected no role for CD98 in chondrocyte mechanotransduction, it may be involved in other biological functions in chondrocyte intracellular signalling events.

Multiple Sclerosis (MS), the most common demylinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some FcγR genes are associated with various infectious and autoimmune diseases, probably due to their effects on different binding capacities of encoded receptors for IgG containing immune complexes. To investigate the importance of FcγR polymorphisms in susceptibility to MS. One hundred and fifty MS patients and 136 age and sex matched controls were genotyped for FcγRIIA and FcγRIIIA gene polymorphisms using PCR-RFLPmethod. The allelic and genotypic frequencies of the FcγRIIA and FcγRIIIA did not differ significantly between the MS patients and controls. There was no associationbetween allelic polymorphism of FcγRIIIA and severity of disease based on Expanded Disability Status Scale (EDSS) score. However, significant association between inherited FcγRIIA genotype and disease activity (p=0.001) or progression index was revealed (p=0.014). EDSS values showed that FcγRIIA (H/H) and (H/R) genotypes were associated with a lower EDSS score in relapsing-remitting MS and in the total MS population (P=0.001) but not (R/R) genotype. Considering the detrimental role of autoantibodies in the pathogenesis of MS, our results suggest that the inherited FcγRIIA alleles could affect the severity of MS by influencing the clearance rate of immune complexes and autoantibodies. The results of the present study add the FcγRIIA gene to the gene networks which determine the severity of MS in southern Iran.

Selenium (Se) is part of the glutathione peroxidase enzyme complex (GSH-PX) that plays an important role in antioxidant mechanisms in body, also it has been demonstrated that populations with low Se intake have 2-3 times greater risk of ischemic heart disease. To determine the circulating levels of IL- 6, TNF-α, Cu, Zn, and Se in patients with chronic coronary artery disease (CCAD), acute myocardial infarction (AMI), and normal individuals. Patients were divided into two groups: 25 subjects with CCAD and 25 patients with AMI. The control group included 50 normal individuals who did not have any history of ischemic heart disease, and were sex and age matched with the patients. Blood samples were collected during the first hours after the onset of chest pain in AMI group. Serum concentration of Se, Cu, and Zn were determined by atomic absorption spectrometry and TNF-α and IL-6 levels were measured using ELISA method. In both groups of patients therewas a significant reduction in serum Se levels (82.36 + 11.31 mg/L in CCAD, 74.08+11.31mg/L in AMI, and 105+32.52mg/L in the control group, P=0.03). TNF-α titers were increased in AMI patients compared with CCAD and control group. Mean TNF-α levels were 37.44 pg/ml in CCAD, 914.32 pg/ml in AMI, and 4.80 pg/ml in the control group (P=0.01). Serum levels of IL-6 in CCAD and AMI patients were 3.28 ±15.55 pg/ml and 472±207.88 pg/ml, respectively, and 1.28 pg/ml in the control group (P=0.001). These findings confirm previous studies and demonstrate thatpatients suffering from AMI exhibit lower plasma concentrations of Se and higher concentrations of pro-inflammatory cytokines of TNF-α and IL-6.

Anti-thyroid peroxidase antibody (anti-TPO antibody) is a member ofthyroid autoantibodies which are important in inducing and also diagnosing autoimmune thyroid diseases. Thyroid autoimmunity can cause several forms of thyroiditis and abnormal thyroid functions, ranging from hypothyroidism to hyperthyroidism. To evaluate the relationship between serum levels of anti-TPO antibody and thyroid function test parameters (T3, T4, and TSH) in patients with thyroid disease. In 2425 subjects suspected of having thyroid disease referred to Yazdcentral medical laboratory by physicians during a 2 year period, the concentrations of serum anti-TPO antibody (ELISA) and T3, T4, and TSH (RIA) were measured. 53.53% of the patients were 20 to 39 years old. 2135 patients (88.04%) were female and 290 (11.96%) were male. The levels of T3, T4, and TSH in individuals with normal and raised anti-TPO antibody titers was significantly different (P<0.0001). A correlation between TSH and T4 levels and abnormal anti-TPO antibody was detected (P=0.002). Our results confirm the correlation between thyroid function test and anti-TPO antibody values, indicating the clinical significance of this antibody and suggesting a through clinical examination and follow up of individuals with high anti-TPO antibody titer.