OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years. The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses. The signaling pathways that involve TNF, type I IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes.
Animals ; Apoptosis ; Autophagy ; Humans ; Interferon Type I ; metabolism ; Macrophages ; immunology ; metabolism ; Mycobacterium tuberculosis ; physiology ; Receptors, Calcitriol ; metabolism ; Steroid Hydroxylases ; metabolism ; Toll-Like Receptors ; metabolism ; Tuberculosis ; immunology ; metabolism ; pathology ; Tumor Necrosis Factors ; metabolism

OBJECTIVETo study the effection of suppression murine melanoma growth by Intratumor injection of recombinant attenuated salmonella carrying heat shock protein 70 and herpes simplex virus thymidine kinase genes.

METHODSPlasmids PCMV-mtHSP70-IRES-TK were electro-transferred into salmonella typhimurium SL7207 to construct recombinant salmonella typhimurium. In vivo, Recombinant bacteria were injected into the mouse melanoma and the antitumor effection was observed. The survival period was recorded and safety analysis for this vaccine in each group.

RESULTSIn vivo, the mtHSP70/HSV-tk recombinant bacteria can suppress tumor growth significantly and extend survival. After recombinant Salmonella, 10(9) CFU/mL, was administered as an intratumoral injection, No diarrhea were observed. During therapy, body weight did not change markedly.

CONCLUSIONResults of the animal experiment suggests intratumor injection of recombinant attenuated salmonella typhimurium containing mtHSP70 and HSV-tk genes, has targeting ability against B16 tumor cell and could significantly inhibit tumor growth .

Animals ; Bacterial Proteins ; genetics ; immunology ; Cancer Vaccines ; genetics ; immunology ; pharmacology ; Genetic Therapy ; methods ; HSP70 Heat-Shock Proteins ; genetics ; immunology ; Melanoma, Experimental ; microbiology ; pathology ; therapy ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis ; genetics ; Salmonella typhimurium ; genetics ; immunology ; Simplexvirus ; enzymology ; genetics ; Skin Neoplasms ; therapy ; Thymidine Kinase ; genetics ; immunology ; Vaccines, Attenuated ; genetics ; immunology ; pharmacology ; Vaccines, DNA ; genetics ; immunology ; pharmacology

OBJECTIVETo explore the clinical manifestation, immune abnormality and outcome of disseminated Bacille Calmette-Guérin (BCG) infection in children.

METHODThe clinical data of 18 children with disseminated BCG infection seen from January 2000 to December 2007 were analyzed retrospectively.

RESULTThirteen of the children were male among 18 patients. Disseminated infection first appeared in armpit lymph nodes ipsilateral to the vaccination site, then spread to lungs in 15, lymphnodes of mediastinum or abdominal cavity in 18, skin and soft tissues in 5, skeletons in 4, liver in 4, spleen in 8, kidney, adrenal gland or meninges in 3. Twelve children were diagnosed to have primary immunodeficiency; 3 had severe combined immunodeficiency (SCID); 7 had chronic granulomatous disease (CGD), 2 had IL-12/IFN-gamma passageway deficiency. Eleven of the 18 patients died, and the remaining 7 patients were followed up from 1 to 9 years and are alive at present, but presented recurrent skin and bone tuberculosis in 4 and recurrent other infection in 3.

CONCLUSIONMost Children with disseminated BCG infection had primary immunodeficiency. CGD and IL-12/IFN-gamma passageway deficiency accounted for considerable proportion, so special immune function should be detected in these patients. The prognosis was poor. The type of the immunodeficiency diseases should be identified in early stage and the specific immune treatment should be given to the patients.

BCG Vaccine ; adverse effects ; Child, Preschool ; Female ; Humans ; Immunologic Deficiency Syndromes ; etiology ; Infant ; Lymph Nodes ; Male ; Mycobacterium bovis ; pathogenicity ; Retrospective Studies ; Tuberculosis ; immunology ; microbiology ; pathology

Natural killer (NK) cell neoplasms are a group of rare but highly malignant tumors. We report here one case of NK cell leukemia. A 54-yr-old woman presented with a 2-month history of progressive left neck mass. Based on the positive result of tissue PCR for Mycobacterium tuberculosis, she was at first diagnosed with tuberculous lymphadenopathy. After two weeks, she developed generalized lymphadenopathy, hepatosplenomegaly, fever and anemia. Subsequent evaluation was performed including bone marrow aspiration and biopsy. Peripheral blood smear showed leukoerythroblastic features with 31% blasts. Bone marrow was packed with agranular blastoid cells, which were periodic acid-Schiff (PAS) positive and myeloperoxidase (MPO) negative. Immunophenotyping showed that these cells were positive for CD45 and HLA-DR, whereas negative for CD3, CD5, CD7, CD10, CD13, CD14, CD19, CD20, CD22, CD33, CD34, and CD61. Because of the absence of the markers of T-cell, B-cell, and myeloid lineage-specific antigens, we added CD16/56 for the immunophenotyping and the blasts were positive (94%). The tumor cells of biopsied lymph node were only positive for CD56, consistent with NK cell lymphoma. Epstein-Barr virus (EBV) was not detected by RNA in situ hybridization. Culture for M. tuberculosis was negative. Thus this patient was diagnosed with blastic NK cell lymphoma/leukemia involving bone marrow and lymph node.
Antigens, CD45/metabolism ; Bone Marrow/pathology ; Female ; HLA-DR Antigens/metabolism ; Humans ; Killer Cells, Natural/immunology/*pathology ; Leukemia/*diagnosis/immunology/pathology ; Middle Aged ; Tuberculosis, Lymph Node/diagnosis

OBJECTIVETo investigate the effects of oral administration of type II collagen (CII) on adjuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CII with those of the Chinese traditional medicine Tripterygium Polyglycoside administered similarly.

METHODSArthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CII or Tripterygium Polyglycoside, changes in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, including delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycobacterium tuberculosis (MT) antibody in serum, and levels of IFN-gamma and TNF-alpha in articular steep in rats.

RESULTSOral administration of CII was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CII were stronger than those by Tripterygium Polyglycoside. Oral administration of CII inhibited antigen-specific immune response, such as DTH and antibody reaction to CII. In addition, the expression of IFN-gamma and TNF-alpha in joints were locally downregulated.

CONCLUSIONSThe therapeutic effect of oral administration of CII is obvious on adjuvant arthritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-gamma and TNF-alpha, and the suppression of cell immunity.

Administration, Oral ; Animals ; Antibodies ; blood ; Arthritis, Experimental ; drug therapy ; immunology ; Collagen Type II ; therapeutic use ; Hypersensitivity, Delayed ; prevention & control ; Immune Tolerance ; Interferon-gamma ; biosynthesis ; Male ; Mycobacterium tuberculosis ; immunology ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; pathology ; Tripterygium ; Tumor Necrosis Factor-alpha ; biosynthesis

Recent studies in man and animal models have demonstrated that TCR-gamma delta-bearing T cells (gamma delta T cells) are activated by mycobacteria and accumulate in the sites of mycobacterial infection. Although the function of gamma delta T cells remains unclear, some data suggest a potential role for these cells in the granulomatous immune response. To address the presence of gamma delta T cells within the BCG granulomas, we have characterized the TCR phenotype of T-lymphocytes present in the BCG granulomatous lesion immunohistochemically using a monoclonal antibody to TCR delta 1 and others. Fairly large numbers of gamma delta T cells were located at the periphery of the BCG granulomas without necrosis and most of them also expressed CD8. However, gamma delta T cells were rarely present in the granulomas with central caseous necrosis, calcification and fibrotic changes. With these results, it might be speculated that the CD8+ gamma delta T lymphocytes participate in the BCG granuloma formation mainly in the early stage.
Female ; Granuloma/immunology/*pathology ; Human ; Infant ; Lymph Nodes/pathology ; Male ; *Mycobacterium bovis ; Receptors, Antigen, T-Cell, gamma-delta/*analysis ; T-Lymphocytes/*immunology ; Tuberculosis/immunology/*pathology

The perchloric acid soluble, heat stable, and ethanol insoluble antigen of M. tuberculosis (TB-PBE) was prepared, and antigenicity of this antigen was studied in vivo and in vitro. TB-PBE showed a single band of 60 kDa by SDS-PAGE. Sera from the patients with active pulmonary tuberculosis did not react with this antigen by ELISA. A delayed hypersensitivity skin reaction was induced with this antigen and was correlated with the reaction with PPD. Skin biopsy was performed in this skin lesion induced by TB-PBE and stained by H-E and immunohistochemical methods. TB-PBE induced an inflammatory lesion similar to a lesion induced by PPD. Blastogenic activity of the peripheral blood mononuclear cells stimulated by TB-PBE increased, and showed a peak reaction at 7 days after stimulation. The blastogenic activity changed in a dose-dependent manner. After stimulation with TB-PBE, mononuclear cells were analyzed by FACS. DR+ T cells and CD4/CD8 ratio increased after stimulation by TB-PBE. These cells secreted IL-2, not IL-4 after stimulation with TB-PBE. In the immunofluorescence test, mouse antiserum against TB-PBE showed a positive reaction with M. tuberculosis and showed cross-reactivity with M. bovive and other atypical mycobacteria, but not with S. aureus. With these results, it is evident that TB-PBE is an antigen which can induce cell mediated immunity in vivo and in vitro.
Animal ; Antigens, Bacterial/immunology/*isolation & purification ; Cytokines/biosynthesis ; Electrophoresis, Polyacrylamide Gel ; Human ; Hypersensitivity, Delayed ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis/*immunology ; Perchloric Acid ; Skin/pathology ; T-Lymphocytes/immunology

The perchloric acid soluble, heat stable, and ethanol insoluble antigen of M. tuberculosis (TB-PBE) was prepared, and antigenicity of this antigen was studied in vivo and in vitro. TB-PBE showed a single band of 60 kDa by SDS-PAGE. Sera from the patients with active pulmonary tuberculosis did not react with this antigen by ELISA. A delayed hypersensitivity skin reaction was induced with this antigen and was correlated with the reaction with PPD. Skin biopsy was performed in this skin lesion induced by TB-PBE and stained by H-E and immunohistochemical methods. TB-PBE induced an inflammatory lesion similar to a lesion induced by PPD. Blastogenic activity of the peripheral blood mononuclear cells stimulated by TB-PBE increased, and showed a peak reaction at 7 days after stimulation. The blastogenic activity changed in a dose-dependent manner. After stimulation with TB-PBE, mononuclear cells were analyzed by FACS. DR+ T cells and CD4/CD8 ratio increased after stimulation by TB-PBE. These cells secreted IL-2, not IL-4 after stimulation with TB-PBE. In the immunofluorescence test, mouse antiserum against TB-PBE showed a positive reaction with M. tuberculosis and showed cross-reactivity with M. bovive and other atypical mycobacteria, but not with S. aureus. With these results, it is evident that TB-PBE is an antigen which can induce cell mediated immunity in vivo and in vitro.
Animal ; Antigens, Bacterial/immunology/*isolation & purification ; Cytokines/biosynthesis ; Electrophoresis, Polyacrylamide Gel ; Human ; Hypersensitivity, Delayed ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis/*immunology ; Perchloric Acid ; Skin/pathology ; T-Lymphocytes/immunology