فهرست مطالب
Iranian journal of immunology
Volume:11 Issue: 2, Spring 2014
- تاریخ انتشار: 1393/04/10
- تعداد عناوین: 8
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Pages 65-73BackgroundLeishmania is a pathogenic parasite which infects mononuclear cells in vertebrate hosts. Different strategies have been taken to develop immunity against Leishmania. DCs loaded with immunogenic antigen have resulted in different levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity.ObjectiveTo evaluate the potency of DCs primed with soluble Leishmania mexicana antigens (SLA) in developing CTL activity.MethodsDCs were loaded with SLA and injected to Balb/c mice. After two weeks the mice were sacrificed and their splenocytes were used as effector cells in a standard 4-hour cytotoxicity assay against DCs transfected with pcDNA3 containing L. mexicana gp63 gene.ResultsImmunization of Balb/c mice with DCs loaded with SLA resulted in high levels of CTL activity against DCs transfected with pcDNA3 containing L. mexicana gp63 gene.ConclusionsThe results indicate a high potency for DCs primed with Leishmania antigens in inducing CTL activity, which can be used for developing an immunogenic vaccine against Leishmania.Keywords: Balb, c, Cytotoxicity, DCs, gp63, Leishmania
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Pages 74-83BackgroundMultiple sclerosis (MS) is a T cell mediated autoimmune disease with unknown etiology. Appropriate MS therapeutic strategies need thorough understanding of both disease etiology and pathogenesis mechanisms. Ligation of TLR-2 and TLR-4 stimulates the production of several cytokines leading to CNS autoimmunity and neurodegenerative diseases.ObjectiveTo find a relationship between MS disability and TLR-2 and TLR-4 expression on mononuclear cells in the blood of MS patients.MethodsForty-five new case (NC) MS patients (33 females and 12 males) and 45 age and gender-matched healthy controls (HC) were recruited to the study. PBMCs were prepared and the expressions of TLR-2 and TLR-4 were assessed by flowcytometry technique using appropriate monoclonal antibodies.ResultsOur results showed that the expression of TLR-2 and TLR-4 proteins in the patients group was significantly higher than that of healthy controls. TLR-2 but not TLR-4 was correlated with expanded disability status scale (EDSS) scores.ConclusionHigh expressions of TLR- 2 and TLR-4 may represent a state of innate immune activation in patients with MS.Keywords: Multiple Sclerosis, TLR2, TLR4, PBMC
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Pages 84-96BackgroundRecurrent spontaneous abortion (RSA) and in vitro fertilization (IVF) failure with unknown causes are the controversial issues that are probably related to the immune system.ObjectiveTo compare circulating NK cells expressing activation and inhibition surface markers between patients with RSA and IVF failure with those of healthy multiparous and successful IVF control women, respectively.MethodsIn this case-control study peripheral blood samples were collected from 43 patients who included 23 women with RSA and 20 with IVF failure, plus 43 healthy control women comprising of 36 normal multiparous women and seven women with successful IVF. The expression of CD69, CD94 and CD161 surface markers on CD56+NK cells were assessed using specific monoclonal antibodies by flowcytometry.ResultsThe percentage of NK cells increased significantly in patients with RSA and in women with IVF failure in comparison to healthy multiparous and successful IVF control groups (p<0.001). The overall expression of CD69, CD94, CD161 were also increased significantly on NK cells in both patient groups compared to control groups (p<0.001).ConclusionElevated expression of CD69 and CD161 on NK cells can be considered as immunological risk markers in RSA and IVF failure. However, it is not clear if high expression of CD94 on peripheral blood NK cells is related to abnormal activity of endometrial NK cells.Keywords: Activation Receptor, IVF Failure, NK cell, RSA
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Pages 97-104BackgroundPro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM).ObjectiveTo investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 A/C, -819 C/T, -1082 A/G), IL-6 (-174 C/G) and IL-17 (-197 G/A) in Iranian women.MethodPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to determine the frequencies of the IL-6, IL-10 and IL-17 gene polymorphisms in 85 women with RM compared with 104 healthy controls.ResultsThe frequencies of IL- 10 promoter gene polymorphisms (-592 A/C and -819 C/T) were significantly higher in RM women than those in controls (p=0.003). However, no statistically significant differences were observed in the frequencies of IL-6 (-174 C/G), IL-10 (-1082 A/G) and IL-17 (-197 G/A) polymorphisms between RM women and controls.ConclusionThese results suggest that IL-10 gene polymorphism screening might have some relevance in patients with RM, a suggestion which requires further studies.Keywords: Cytokine, Gene Polymorphism, PCR, RFLP, Recurrent Miscarriage
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Pages 105-112BackgroundOvarian cancer is the fifth leading cause of death from malignancy in women. CD4+CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response.ObjectivesTo investigate the percentage of CD4+CD25+FoxP3+ regulatory T cells in the peripheral blood of the Iranian patients with epithelial ovarian cancer compared to healthy women and to evaluate the correlation of the Treg cell percentage with clinicopathological characteristics including cancer stage and CA-125 serum level.MethodsSeventeen women with epithelial ovarian cancer and 20 healthy subjects were enrolled in the study. Peripheral blood mononuclear cells were stained at the surface, for CD4 and CD25 molecules, followed by fixation, permeabilization and intracellular staining for FoxP3 molecule. After processing and flowcytometry analysis, prevalence of Treg cells was determined as the percentages of CD25+FoxP3+ cells among CD4+ lymphocytes.ResultsDespite no difference in the percentage of total CD4+ lymphocytes, analysis indicated that Treg cell percentage was significantly higher in ovarian cancer patients than controls (5.7 ± 3.1% versus 2.8 ± 1.4%, p=0.002). A trend toward higher Treg cells was observed in higher stages of ovarian cancer (III+IV) in comparison to lower stages (I+II) (6.5 ± 3.2% vs. 4.44 ± 2.7%, p=0.2). Higher percentage of Treg cells was also observed in the patients with high CA125 (CA-125 >100 U/mL) in comparison to those with low CA-125 serum level (CA-125 ≤ 100 U/mL) although the difference was not significant (6.44 versus 4.18%, p=0.19).ConclusionIncreased frequency of Tregs in ovarian cancer might participate in immune suppression in these patients. The findings collectively suggest the likely impact of Treg cell–targeted immunotherapy in ovarian cancer.Keywords: Flowcytometry, Ovarian Cancer, Treg
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Pages 113-122BackgroundPropylene glycol (1,2-propanediol, PG) is a commonly used solvent for oral, intravenous, as well as topical pharmaceutical preparations. While PG is generally considered to be safe, it has been known that large intravenous doses given over a short period of time can be toxic.ObjectiveTo evaluate the effect of PG in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS).MethodsBalb/c mice were treated with LPS (1 mg/kg b.w., i.p.) with or without PG (5 g/kg b.w. i.v.). The survival rate and the production of inflammatory cytokines were measured. In RAW264.7 mouse macrophages encoding NF-B-luc reporter gene, the nuclear transcription factor kappa- B (NF-B) activation was measured.ResultsWe found that intravenous PG increased the mortality rate in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS) in mice. In accordance with that, PG enhanced LPS-induced production of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vivo. PG also increased the LPS-induced macrophage activation in vitro as detected by measuring NF-B activation.ConclusionOur results indicate that drugs containing high doses of PG can pose a risk when administered to patients suffering from or prone to Gram negative bacterial infection.Keywords: Inflammation, NF, B, Propylene, Glycol, Sepsis
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Pages 123-133BackgroundDefects in B cell class switch recombination (CSR) are a heterogeneous and yet very uncommon group of disorders which all have a genetic basis uniformly leading to hyper IgM (HIgM) syndrome. Due to the rare frequency of these conditions, a very small number of case series have been conducted on the affected patients.ObjectiveTo shed some light on the morbidity and mortality regarding a relatively large cohort of diagnosed CSR defective Iranian patients.MethodsThis study was performed using demographic information, laboratory findings and clinical data obtained from an observation of 33 Iranian patients of different ethnicities referred from all medical centers of Iran to the Children’s Medical Center Hospital, pediatrics center of excellence, Tehran, Iran; of which 28 were males and 5 were females.ResultsOur patients mean age at the onset of symptoms was 1.8 ± 0.2 years; they were diagnosed with a mean delay of 4.4 ± 3.3 years and followed for a mean time of 5.7 ± 4.8 years. The most prominent clinical features observed were multi-organ infections, affecting mostly the respiratory system, followed by lymphoproliferative and autoimmune disorders, the latter being of much higher frequency (44%) in our study than the reported frequency in previous reports. The three year survival rate for our enrolled patients was 67.9%.ConclusionsBased on our findings, the most common cause of death in HIgM patients is respiratory failure. The molecular mechanism behind the nature of the CSR defective patients in Iran is more compatible with autosomal recessive mutations rather than X-linked HIgM syndrome which is in contrast with other large cohorts of patients with CSR defect.Keywords: Class Switch Recombination, Clinical Manifestation, Hyper IgM Syndrome
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Pages 134-138BackgroundMidkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration.ObjectiveTo study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients.MethodsWe evaluated the MK level and its relationship with inflammatory cytokines (IL-17 and IL-23) and antiinflammatory ones (IL-10 and TGF-β) in multiple sclerosis (MS) patients. The serum concentrations of MK and cytokines were assessed by ELISA in 32 MS patients in comparison with 32 healthy subjects.ResultsOur data showed that the MK concentration in MS patients is lower than healthy controls (341.15 ± 40.71 Pg/ml vs. 620.15 ± 98.61 Pg/ml, respectively, p=0.015). We also observed a significant decrease in IL-10, IL-23, and TGF-β cytokine levels in MS patients. There was a significant correlation between MK and IL-23 concentrations in our study (r = +0.829, p≤ 0.001).ConclusionThese results confirm a role for MK in inflammatory reactions in MS.Keywords: IL, 10, IL, 17, IL, 23, Midkine, Multiple Sclerosis, TGF, beta