Chronic granulomatous disease (CGD) is a very rare disease whose defect lies in an abnormal intracellular killing resulting in recurrent abscesses, lymphadenitis and granuloma formation. We describe 2 Malay male infants with CGD whom we believe to be the first report of this disorder in Malays. Both children presented with recurrent abscesses, pneumoniae and hepatosplenomegaly; lymphadenopathy was also present in one of the patients. The organisms isolated were catalase positive bacteria. Both neutrophil chemiluminescence (against fungal and bacterial antigens, phorbol myristate acetate) and intracellular killing assays were severely depressed. Recognition of CGD is important as great strides have been made in the treatment of this disease which include gamma interferon therapy besides the conventional prophylactic antibacterial therapy.
Anti-Bacterial Agents ; therapeutic use ; Fatal Outcome ; Granulomatous Disease, Chronic ; diagnosis ; drug therapy ; immunology ; Humans ; Immunity, Cellular ; Infant ; Interferon-gamma ; therapeutic use ; Malaysia ; Male ; Phagocytosis

Autoimmune Diseases ; drug therapy ; pathology ; Cholangitis ; drug therapy ; immunology ; pathology ; Cholangitis, Sclerosing ; drug therapy ; immunology ; pathology ; Hepatitis, Autoimmune ; drug therapy ; immunology ; pathology ; Humans ; Interferon-gamma ; therapeutic use ; Liver Cirrhosis, Biliary ; drug therapy ; immunology ; pathology ; Ursodeoxycholic Acid ; therapeutic use

PURPOSE: To identify new immunogenic HLA-A*33;03-restricted epitopes from the human papillomavirus (HPV) 16 E7 protein for immunotherapy against cervical cancer. MATERIALS AND METHODS: We synthesized fourteen overlapping 15-amino acid peptides and measured intracellular interferon-γ (IFN-γ) production in PBMC and CD8+ cytotoxic T lymphocytes (CTLs) after sensitization with these peptides using flow cytometry and ELISpot assay. The immunogenicity of epitopes was verified using a ⁵¹Cr release assay with SNU1299 cells. RESULTS: Among the fourteen 15-amino acid peptides, E7₄₉₋₆₃ (RAHYNIVTFCCKCDS) demonstrated the highest IFN-γ production from peripheral blood mononuclear cells (PBMCs), and CD8+ CTLs sensitized with E7₄₉₋₆₃ showed higher cytotoxic effect against SNU1299 cells than did CD8+ CTLs sensitized with other peptides or a negative control group. Thirteen 9- or 10-amino acid overlapping peptides spanning E7₄₉₋₆₃, E7₅₀₋₅₉ (AHYNIVTFCC), and E7₅₂₋₆₁ (YNIVTFCCKC) induced significantly higher IFN-γ production and cytotoxic effects against SNU1299 cells than the other peptides and negative controls, and the cytotoxicity of E7₅₀₋₅₉- and E7₅₂₋₆₁-sensitized PBMCs was induced via the cytolytic effect of CD8+ CTLs. CONCLUSION: We identified E7₅₀₋₅₉ and E7₅₂₋₆₁ as novel HPV 16 E7 epitopes for HLA-A*33;03. CD8+ CTL sensitized with these peptides result in an antitumor effect against cervical cancer cells. These epitopes could be useful for immune monitoring and immunotherapy for cervical cancer and HPV 16-related diseases including anal cancer and oropharyngeal cancer.
Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Epitopes/*immunology/therapeutic use ; Female ; *HLA-A Antigens ; Human papillomavirus 16/*immunology ; Humans ; *Immunotherapy ; Interferon-gamma/analysis/*biosynthesis ; Leukocytes, Mononuclear/immunology/metabolism ; T-Lymphocytes, Cytotoxic/immunology/metabolism ; Uterine Cervical Neoplasms/*therapy

The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections.
Animals ; Bacterial Vaccines/immunology/*microbiology/*therapeutic use ; Extracellular Vesicles/immunology/*microbiology ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Interferon-gamma/immunology ; Klebsiella Infections/immunology/*prevention &control ; Klebsiella pneumoniae/*immunology ; Mice, Inbred C57BL ; Vaccination

OBJECTIVETo study the pathogenesis of IgA nephropathy (IgAN) and the effect of Yiqi Zishen Granule (YZG) on the helper T-lymphocyte subsets Th1/Th2 in IgAN patients.

METHODSIntracellular cytokines secreted by Th1/Th2 were measured using flow cytometry in 24 healthy subjects and 31 IgAN patients treated by YZG before and after treatment.

RESULTSLevel of interferon-gamma (IFN-gamma) was lower (P < 0.05) and levels of interleukin 4 (IL-4) and interleukin 10 (IL-10) were higher (P < 0.01) in the IgAN patients than those in the healthy controls, showing imbalance of Th1/Th2 in the IgAN patients. After YZG treatment, the level of IFN-gamma increased and IL-10 level decreased (P < 0.01).

CONCLUSIONImbalance of Th1/Th2 exists in IgAN patients. YZG has a regulatory effect on imbalance of Th1/Th2 in IgAN patients.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glomerulonephritis, IGA ; drug therapy ; immunology ; Humans ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Male ; Phytotherapy ; Powders ; T-Lymphocytes, Helper-Inducer ; drug effects

OBJECTIVETo investigate the clinical and pathological characteristics of primary cervical malignant melanoma, and its prognosis.

METHODSThe clinical and pathological data of four patients with primary malignant melanoma of the cervix were analyzed retrospectively. Nerve tissue protein S-100 and monoclonal antibody to melanoma (HMB-45) were measured in all cases by immunohistochemical method. All four patients received radical hysterectomy. Three of them received chemotherapy preoperation or postoperation, and one of them received biotherapy with interferon-gamma and interleukin-2 at the same time. All the cases were followed up.

RESULTSThe average age of four patients was 45 years. Clinical symptoms presented with irregular vaginal bleeding, postcoital bleeding, or increase of vaginal discharge. Gynecologic examination showed polypus papilla cauliflower-shaped or nodulated black-brown or black-blue mass on the cervix. All the four cases were pathologically diagnosed with cervical malignant melanoma. S-100 and HMB-45 were positive in all patients. Two patients died at 6 and 41 months postoperation, respectively. The other two patients survived for 3.5 and 7 years postoperation, respectively.

CONCLUSIONSS-100 protein and HMB-45 play very important roles in the diagnosis of primary malignant melanoma of cervix. Radical hysterectomy, chemotherapy combined with dimethyl triazemo imidazole carboxamide and biological therapies may improve the prognosis of the primary malignant melanoma of cervix if the disease could be diagnosed in an early stage.

Adult ; Antibodies, Monoclonal ; metabolism ; Chemotherapy, Adjuvant ; Dacarbazine ; therapeutic use ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Interferon-gamma ; therapeutic use ; Melanoma ; immunology ; pathology ; therapy ; Middle Aged ; Prognosis ; Retrospective Studies ; S100 Proteins ; metabolism ; Uterine Cervical Neoplasms ; immunology ; pathology ; therapy

OBJECTIVETo investigate the effect of Astragalus in regulating the imbalance between naive helper T cells (Th1/Th2) cytokines expression in patients with cervical cancer.

METHODSThirty patients with cervical cancer received intravenous dripping with 20 mL of Astragalus Injection (AI, contained extract from 40 g of crude drug) per day for 1 week, peripheral blood sample was collected from patients separately before and after treatment for extract mononuclear cells by density gradient centrifugation. The positive percentages of CD4+ interferon-gamma (IFN-gamma ) cell and CD4+ interleukin-4 (IL-4) cell in total CD4+ cells were measured by flow cytometry; the contents of IFN-gamma, IL-4 in culture supernate were detected with ELISA; and the expressions of T-cell transcription factor T-cells (T-bet) and GATA-binding protein-3 (GATA-3) were determined by RT-PCR. The data were controlled by those get from 10 healthy persons.

RESULTSCD4+ IFN-gamma positive cell percentage, T-bet mRNA expression level and concentration of IFN-gamma in supernate were significantly lower in patients than those in healthy control respectively, while CD4+ IL-4 positive percentage, level of GATA3 mRNA expression and IL-4 concentration in supernate were insignificantly different between the two groups. After AI treatment, the lowered parameters were up-regulated (P < 0.05), and no obvious change was observed in the CD4+ IL-4 positive cell associated parameters.

CONCLUSIONTh1/Th2 cell function imbalance existed in patients with cervical cancer, showing a Th2 predominant reaction mode; AI can regulate the imbalance, offset to Th1, thus to display its anti-tumor effect.

Aged ; Astragalus membranaceus ; chemistry ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Middle Aged ; Phytotherapy ; Th1-Th2 Balance ; drug effects ; Uterine Cervical Neoplasms ; drug therapy ; immunology

OBJECTIVETo observe the effect of Yangyin Yiqi Huoxue Recipe (YYHR) on expression of interferon-gamma (IFN-gamma), IL-2, IL-4, IL-10, and immune balance of Th1/Th2 in serum and submaxillary glands of non-obese diabetic (NOD) mice with Sjogren's syndrome (SS), and to explore its mechanisms.

METHODSTotally 32 NOD mice were randomly into 4 groups, i.e., the model group, the Chinese medicine group [CM, administered with YYHR at the dose of 0.4 mL by gavage (100 g/kg)], the Western medicine group [WM group, administered with hydroxychloroquine 0.4 mL by gavage (60 mg/kg)], and the combined group [administered with YYHR (50 g/kg) and hydroxychloroquine (60 mg/kg) 0.4 mL by gavage], 8 mice in each group. Eight Balb/C mice were recruited as the normal control group. Mice were sacrificed to withdraw blood after 8 weeks. The submaxillary gland was excised. Serum levels of IFN-gamma, IL-2, IL-4, and IL-10 were detected by ELISA. Protein expression of IFN-gamma, IL-2, IL-4, and IL-10 in submaxillary glands was detected by SP method.

RESULTSCompared with the normal group, levels of IFN-gamma, IL-2, IL-4, and IL-10 in serum and submaxillary glands all increased in the model group (P < 0.05). Levels of IFN-gamma and IL-10 in serum in the CM group and the combined group were lower than those of the WM group (P < 0.05). Serum levels of IFN-gamma and IL-2 in submaxillary glands in combined group were lower than those of the WM group (P < 0.05). The ratio of IFN-gamma/IL-4 in serum and submaxillary glands in the model group were higher than that of the rest groups (P < 0.05). Besides, it was the nearest to that of the normal group.

CONCLUSIONSYYHR could decrease the levels of Th1 and Th2 related cytokines and the ratio of IFN-gamma/IL-4 in serum and submaxillary glands of NOD mice with SS. It could achieve therapeutic effects through adjusting immune balance of Th1/Th2 in SS mice.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interferon-gamma ; blood ; Interleukins ; blood ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Serum ; immunology ; Sjogren's Syndrome ; blood ; drug therapy ; immunology ; Submandibular Gland ; immunology ; Th1-Th2 Balance

OBJECTIVETo investigate the effect of pulmonary surfactant (PS) on the Th1/Th2 balance and serum levels of interleukin-4 (IL-4), interferon-&gamma; (IFN-&gamma;) and IgE in neonates with respiratory distress syndrome (RDS).

METHODSA total of 58 neonates with RDS were divided into control (n=20) and PS treatment groups (n=38). The control group underwent mechanical ventilation and other conventional treatment, while the PS treatment group received with bovine PS treatment within 1 hour of being admitted to the hospital together with mechanical ventilation and other conventional treatment. Enzyme-linked immunosorbent assay was used to measure serum levels of IL-4, IFN-&gamma; and IgE before treatment and 24, 48 and 72 hours after treatment. Simultaneously, arterial blood gas, respiratory system compliance, and other ventilator parameters were recorded.

RESULTSCompared with the control group, the PS treatment group showed significantly shorter duration of mechanical ventilation and oxygen exposure time (P<0.05), significantly better respiratory system compliance and significantly lower oxygenation index 24, 48 and 72 hours after treatment (P<0.05). At 48 and 72 hours after treatment, serum levels of IFN-&gamma; were significantly lower in the PS treatment group than in the control group (120±46 ng/L vs 229±59 ng/L, P<0.05; 141±40 ng/L vs 282±44 ng/L, P<0.05), and serum levels of IL-4 were significantly higher in the PS treatment group than in the control group (263±48 pg/mL vs 152±45 pg/mL, P<0.05; 417±49 pg/mL vs 201±46 pg/mL, P<0.05). At 72 hours after treatment, serum level of IgE was significantly lower in the PS treatment group than in the control group (115±44 pg/mL vs 199±43 ng/mL; P<0.05).

CONCLUSIONSPS treatment can shorten the duration of mechanical ventilation and oxygen exposure time, regulate serum levels of IFN-&gamma;, IL-4 and IgE, and influence Th1/Th2 balance in neonates with RDS, thus inhibiting lung inflammatory response and reducing lung injury.

CD4 Lymphocyte Count ; Female ; Humans ; Immunoglobulin E ; blood ; Infant, Newborn ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Pulmonary Surfactants ; pharmacology ; therapeutic use ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; complications ; drug therapy ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVEDingchuantang is a traditional Chinese medicine decoction which has the Qing, Xuan and Jiang components which have the ability to dispel (Xuan), depress (Jiang) and heat clear or febrigugal (Qing). It has been used for asthma and respiratory syncytial virus (RSV) infection. However, the therapeutic mechanisms of the decoction have not been identified. To understand the mechanism of the anti-RSV property of Dingchuantang, this study investigated the effects of Dingchuantang and its three components on the levels of interleukin-4 (IL-4) and interferon-gamma (gamma-IFN) in mice infected by RSV.

METHODSOne hundred and twenty mice were randomly assigned into Normal, Infected, Dingchuantang-treated, Qing component-treated, Xuan component-treated and Jiang component-treated groups (n=20 each). The RSV infection model was prepared in the rats from the last 5 groups. The 4 treatment groups were administered with Dingchuantang, Qing component, Xuan component and Jiang component by gastric lavage respectively 2 hrs after RSV innoculation. The contents of RSV in the lungs were tested by reverse transcription polymerase chain reaction (RT-PCR). The levels of IL-4 and gamma-IFN in broncho-alveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA).

RESULTSThe contents of RSV of lungs in the Dingchuantang-treated group, and Qing and Xuan component-treated groups were significantly lower than those in the untreated Infected group. There was no significant difference between the Jiang component-treated and the Infected group. Dingchuantang treatment decreased the IL-4 level and increased the gamma-IFN level. The Xuan and Jiang component treatment decreased the IL-4 level but had no effect on the gamma-IFN level, while the Qing component treatment increased the gamma-IFN level but had no effect on the IL-4 level.

CONCLUSIONSDingchuantang can inhibit RSV reproduction and this effect works by Qing and Xuan components. Dingchuantang can also restore the imbalance TH2/TH1 by depressing IL-4 levels, worked by Xuan and Jiang components, and increasing gamma-IFN levels, worked by Qing component.

Animals ; Female ; Interferon-gamma ; biosynthesis ; Interleukin-4 ; biosynthesis ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; therapeutic use ; Respiratory Syncytial Virus Infections ; drug therapy ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology