Iranian Journal of Immunology

Abstract Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japa-nese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne diseases such as malaria, dengue infection and West Nile virus infection. In this article, the author reviews the issues on vaccination of some important tropical mosquito borne infectious diseases.

Abstract Background: Type-I diabetes is an autoimmune inflammatory disease in which pancreatic ß-cells are selectively destroyed by infiltrating cells. TNF-related apoptosis-inducing ligand (TRAIL) is a type-II membrane protein of the TNF superfamily which is expressed in different tissues, including pancreas and lymphocytes. In humans, TRAIL interacts with four membrane receptors. TRAIL-R1 and TRAIL-R2 have cytoplasmic death domains, and can activate both caspases and NFκB pathways. The other two receptors, TRAIL-R3 and TRAIL-R4, are decoy receptors not capable of activating caspase cascade but may activate NF-κB and block apoptosis. As human beta cells are sensitive to TRAIL induced apoptosis, signaling via these molecules is considered to be a probable way of beta cell destruction. These molecules also are important in suppression of autorective T cells and immunoregulation.
Objective: To explore the importance of TRAIL and its receptors at pathogenesis of type-I diabetes, we compared expression of these molecules on T-cells of diabetic patients and healthy controls.
Methods: In this study, expression of TRAIL and its receptors at protein and mRNA levels were studied in freshly isolated peripheral T cells of 55 type I diabetic patients and 50 healthy individuals by flowcytometry, western blot and RT-PCR.
Results: We found that expression of TRAIL and its receptors in peripheral T-cells at both protein and mRNA levels are significantly increased in patients (except for TRAIL-R2 mRNA which was slightly higher in controls) but increase in TRAIL, TRAIL-R3 (2.7% vs. >0.5%) and TRAIL-R4 (2.6% vs. >0.5%) is more considerable. sTRAIL in sera of patients was significantly lower than in controls (p=0.01).
Conclusion: Our results explain resistance of autoreactive T-cells to immunoregulatory mechanisms. Besides, increased expression of TRAIL in autoreactive T-cells may play an important role in beta-cell destruction. Lower level of sTRAIL in diabetic patients may be a reason for hyperactivation of autoreactive T-cells.

Abstract Background: Lung carcinoma is a multiple type cancer comprising of small cell and non-small cell carcinomas (NSCLC). For therapeutic and diagnostic purposes, serum monoclonal antibodies have been produced against lung cancer.
Objective: To charac-terize a murine monoclonal antibody (ME3D11) reactive with human NSCLC.
Methods: A murine monoclonal antibody (ME3D11) reactive with human NSCLC was selected after immunization of BALB/c mice with a human large cell carcinoma with neuroen-docrine differentiation, and was tested by immunofloursence staining and Western blot analysis.
Results: Our study showed that the antigen recognized by ME3D11 antibody was a cell surface antigen of 170kDa. This antigen is expressed on the cell surface of all NSCLC and a few carcinoma cell lines. In contrast, this antigen is neither expressed on the cell surface of human sarcoma, nor on the hematopoietic and normal cell lines. This anti-body had no effect on spontaneous proliferation of Mehr-80 cell line in vitro.
Conclusion: High degree of binding of this monoclonal antibody to NSCLC and some other carci-noma cells warrants further studies on its potential use in diagnosis and therapy of can-cer by conjugation to drugs, toxins or radionuclides.

Abstract Background: Glaucoma is one of the most common causes of blindness and is usually associated with elevated intraocular pressure. In patients with primary open angle glau-coma the number of trabecular meshwork cells is decreased. Death of the trabecular meshwork cells may be a result of apoptosis.
Objective: To investigate the aqueous humor levels of soluble Fas (sFas) and Fas-Ligand (sFasL) in glaucomatous patients.
Methods: Concentration of sFas and sFasL were measured by ELISA in 41 eyes with glaucoma (21 with pseudoexfoliation and 20 with primary open angle glaucoma) and 39 eyes with cataract as controls.
Results: The sFas concentration was lower in the pri-mary open angle than the pseudoexfoliation glaucoma and the cataract groups (p=0.002 and p= 0.004, respectively). The sFasL level did not show any significant difference in the three groups.
Conclusion: A lower level of sFas may provide proper microenvironment for increased apoptosis of trabecular meshwork cells in primary open angle glaucoma.

Abstract Background: The water-soluble extract of Ganoderma lucidum (Reishi) has been used as an immunomodulator to stimulate spleen cells proliferation and cytokine expression.
Objective: To investigate the effect of Ganoderma lucidum (G. lucidum) on cytokine production by mice peritoneal macrophages.
Methods: Mice peritoneal macrophages were prepared by intra-peritoneal injection of 5 ml cold PBS. Peritoneal macrophages were plated out at 1X106 cell/well in 1ml RPMI 1640 medium supplemented with 10%FCS, 50 μg streptomycin and 50U penicillin. Cells were incubated in the presence or absence of different concentrations of G. lucidum at 370C and 5% CO2 for 48 hours. Cell free medium was removed and used for cytokine assay by ELISA method (Bender med system).
Results: The results showed no significant differences in cell viability at concentrations ranged from 0-40 μg/ml compared with control group. G. lucidum enhanced IL-1β, TNF-α and NO production in a concentration dependent manner. However, it is not clear if the enhancement of NO release is due to direct effect of G. lucidum on NO synthesis or by indirect endogenous modulation via cytokines. IL-12 release by peritoneal macrophages was also increased in response to different concentrations of G. lucidum, but maximum enhancement was induced in response to 5 μg/ml of G. lucidum (p<0.001).
Conclusion: Our results indicate that G. lucidum at concentrations used has a positive effect on cytokine release and NO production by peritoneal macrophages. Therefore, it is concluded that G. lucidum at moderate concentrations improves macrophage function through cytokine and NO release.

Abstract Background: Inflammation plays a critical role in atherogenesis. The initial step in atherosclerosis is the adhesion of leukocytes to activated endothelial cells mediated by ICAM-1, an inflammatory protein. Several polymorphisms for Intracellular adhesion molecule -1(ICAM-) gene have been described.
Objective: To determine the possible role of G241R and K469E polymorphisms in development of coronary artery disease and MI.
Methods: G241R polymorphism was investigated in 303 patients with angiographi-cally documented CAD, including 151 patients with acute or chronic myocardial infarc-tion (MI), and a control group consisting of 141 healthy subjects with normal coronary angiogram. K469E polymorphism was investigated in 309 patients with CHD, includ-ing155 patients with MI, and compared with 150 healthy subjects without CHD as the control group. Finally, G241R and K469R polymorphisms were assessed concurrently in 300 patients with CHD including 152 patients with MI and 140 healthy normal subjects without coronary heart disease (CHD).
Results: Although the frequency of GR and RR genotypes were higher in the control group compared to the CHD patients, the difference was not statistically significant (7.09% vs. 5.6% and 1.4% vs. 0%, p=0.27and p=0.24, re-spectively). Despite the higher frequency of KK genotype in the CHD group, the differ-ence was not significant (29.1% vs. 24.6%, p=0.62). KKGG genotype was more frequent in the CHD group, however the difference was not significant (31.1% vs. 27.3%, p=0.66).
Conclusion: No strong relation was found between G241R and K469E polymorphisms and occurrence of CHD and MI in the studied population from Fars province, Iran.

Abstract Background: Although many experimental studies provide convincing evidence that type II immunity is protective against helminths, recent data in mice demonstrate that Th1 is also impor-tant in some cestodes like Hymenolepis nana.
Objective: To identify the role of Th1 and Th2 lymphocytes in immunity against H. nana, the levels of IL-12, IFNγ, IL-5, and IL-13 were de-termined in serum of humans infected with this cestode.
Methods: A total of 31 patients (case) with H. nana infection and 30 clinically healthy individuals (control) was included in this study. Measurements of IL-12, IFNγ, IL-13 and IL-5 in serum samples were performed by solid-phase sandwich enzyme linked immunosorbant assay. Differential leukocyte count was also done. T test, Mann Whitney U test and Wilcoxan W test were used for data analysis.
Results: The mean concentrations of IFNγ, IL-12 and IL-5 in the sera of patients with H. nana infection were higher than the control group, but only the differences between the concentrations of IFNγ (p<0.001) and IL-13 (p<0.05) in the two groups were significant. There was an increase in the percentage of monocytes, eosinophils and lymphocytes in patients when compared to the controls, but this increase was not significant.
Conclusion: Results from the present study in humans are in agree-ment with experimental studies in animals in which both Th1 and Th2 responses occur in H. nana infection.

Abstract Background: Papillon-Lefevre Syndrome (PLS) is a rare autosomal recessive disorder characterized by diffused palmoplantar keratoderma and severe periodontitis. Increased susceptibility to infections due to impairment of the immune system is considered to be involved in pathoetiology of this disease.
Objective: According to the crucial function of HLA molecules in immune responses and association between certain HLA class I alleles and some periodontal or skin diseases, this study was designed to evaluate the relation of HLA class I genes and PLS.
Method: HLA class I genes were typed by PCR-SSP (Polymerase Chain Reaction with Sequence Specific Primers) method in eight Iranian PLS patients and 89 healthy controls.
Results: The results showed no sig-nificant difference between the patients and controls. Moreover, identical haplotypes or genotypes were also observed among PLS patients and their healthy siblings. Conclu-sion: It seems that further genes are involved in genetic susceptibility to PLS. However the results of this study showed no significant association between HLA class I genes and PLS, molecular analyses of killer immunoglobulin-like receptors (KIRs) and MHC class I chain-related gene A and B (MICA/B) in PLS may clear many obscure points about the genetic factors involved in these diseases.