慢性阻塞性肺疾病合并肺结核患者体液和细胞免疫功能的研究
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摘要
第一部分慢性阻塞性肺疾病合并肺结核患者体液免疫功能的研究
目的：慢性阻塞性肺疾病（COPD）易患结核病，然而，其确切机制尚未阐明。免疫机制可能参与了COPD伴发肺结核的发生与发展中，但相关研究很少，尤其是COPD合并肺结核患者体液免疫功能的研究更少。通过对COPD合并肺结核患者血清IgG、IgM和IgA的水平进行检测，了解其体液免疫功能状态，探讨COPD患者易患结核病的免疫发生机制。
方法：对2009年1月至2012年3月在上海市肺科医院的COPD合并肺结核患者（COPD合并TB组）、肺结核患者（TB组）以及COPD患者（COPD组）和正常健康人（健康对照组）的体液免疫功能进行对比分析。采用免疫比浊法检测各组血清中IgM、IgG、IgA含量。数据的结果应用SPSS15.0统计学软件(SPSS Inc., IL)进行分析。四组间的比较采用的是K个独立样本的非参数检验中的Kruskal-Wallis检验。两组间的比较采用的是两个独立样本的非参数检验中的Mann-Whitney U检验。不同参数的相关性通过Spearman’s等级相关系数来确定。P＜0.05为差异有统计学意义。
结果：该研究共入选152例COPD合并肺结核患者、157例COPD患者、150肺结核患者以及50例正常健康人。COPD合并TB组血清IgG水平明显高于COPD组，差异有统计学意义（Z=-2.826，P=0.005）。TB组血清IgG水平明显高于COPD组，差异有统计学意义（Z=-2.595，P=0.009）。COPD合并TB组IgA含量明显高于COPD组，差异有统计学意义（Z=-3.377，P=0.001）。COPD合并TB组IgA含量明显高于健康对照组，差异有统计学意义（Z=-2.955，P=0.003）。TB组IgA含量明显高于COPD组，差异有统计学意义（Z=-3.640，P=0.000）。TB组IgA含量明显高于健康对照组，差异有统计学意义（Z=-3.066，P=0.002）。
结论：COPD合并TB患者IgG和IgA水平均明显升高，这种增强的体液免疫应答在COPD并发肺结核发生过程中可能对机体起到一定的保护作用。
第二部分慢性阻塞性肺疾病合并肺结核患者T淋巴细胞及NK细胞的变化及其意义
目的：T淋巴细胞、自然杀伤（NK）细胞均参与了结核病及COPD的免疫发病过程。然而，这些细胞在COPD合并肺结核患者中的表达情况如何却知之甚少。为此，我们对COPD合并肺结核患者T淋巴细胞和NK细胞的水平进行检测，以探讨这些细胞在COPD合并结核病发生发展过程中的作用和意义。
方法：对2009年1月至2012年3月在上海市肺科医院的COPD合并肺结核患者（COPD合并TB组）、肺结核患者（TB组）以及COPD患者（COPD组）和正常健康人（健康对照组）的免疫细胞水平进行对比分析。采用流式细胞仪（BDAccuri C6）抗体双标法测定NK细胞及T淋巴细胞亚群及其比率。数据的结果应用SPSS15.0统计学软件(SPSS Inc., IL)进行分析。四组间的比较采用的是K个独立样本的非参数检验中的Kruskal-Wallis检验。两组间的比较采用的是两个独立样本的非参数检验中的Mann-Whitney U检验。不同参数的相关性通过Spearman’s等级相关系数来确定。P＜0.05为差异有统计学意义。
结果：该研究共入选152例COPD合并肺结核患者、157例COPD患者、150肺结核患者以及50例正常健康人。COPD合并TB组、TB组和COPD组血清CD4+T细胞比率均低于健康对照组，差异有统计学意义（P≤0.001）。TB组血清CD4+T细胞比率明显高于COPD合并TB组，差异有统计学意义（P=0.02）。COPD合并TB组、TB组和COPD组血清CD8+T细胞比率均高于健康对照组，差异有高度统计学意义（P=0.000）。COPD合并TB组、TB组和COPD组血清CD4+/CD8+T细胞比值均低于健康对照组，差异有统计学意义（P=0.000）。TB组血清NK细胞比率明显低于其他各组，差异有统计学意义（P=0.000）。COPD合并TB组和COPD组之间NK细胞比率差异也无统计学意义（P>0.05），COPD合并TB组和健康对照组之间NK细胞比率差异无统计学意义（P>0.05），COPD组和健康对照组之间NK细胞比率差异无统计学意义（P>0.05）。
结论：COPD合并TB患者血清CD4+T细胞比率、CD4+/CD8+T细胞比值均低于健康对照组， CD8+T细胞比率均高于健康对照组。表明，COPD合并肺结核患者细胞免疫功能受损。CD4+T细胞比率、CD4+/CD8+T细胞比值降低以及CD8+T细胞比率升高可能是其重要免疫发病机制之一。
第三部分慢性阻塞性肺疾病合并肺结核患者细胞因子的变化及其意义
目的：多种CK参与结核病及COPD的免疫应答及免疫发病过程。然而，这些细胞因子在COPD合并肺结核患者中的表达状态和特征如何却知之甚少。为此，我们对COPD合并肺结核患者血清细胞因子水平进行检测，以探讨这些细胞因子在COPD合并结核病发生发展过程中的作用和意义。
方法：对2009年1月至2012年3月在上海市肺科医院的COPD合并肺结核患者（COPD合并TB组）、肺结核患者（TB组）以及COPD患者（COPD组）和正常健康人（健康对照组）的细胞因子水平进行对比分析。采用双抗体夹心ELISA方法测定患者血清中IL-1、IL-5、IL-6、sIL-2R、TNF-、IFN-γ等细胞因子水平。数据的结果应用SPSS15.0统计学软件(SPSS Inc., IL)进行分析。四组间的比较采用的是K个独立样本的非参数检验中的Kruskal-Wallis检验。两组间的比较采用的是两个独立样本的非参数检验中的Mann-Whitney U检验。不同参数的相关性通过Spearman’s等级相关系数来确定。P＜0.05为差异有统计学意义。
结果：该研究共入选152例COPD合并肺结核患者、157例COPD患者、150肺结核患者以及50例正常健康人。COPD合并TB组IL-1水平明显低于健康对照组，差异有统计学意义（P=0.002）。TB组IL-1水平明显低于健康对照组（P=0.003）。COPD组IL-1水平明显低于健康对照组（P=0.000）。COPD合并TB组以及TB组sIL-2R水平均明显高于健康对照组（P=0.000）。COPD合并TB组sIL-2R水平明显高于TB组（P=0.041）。COPD合并TB组sIL-2R水平明显高于COPD组（P=0.000）。COPD合并TB组IL-5水平明显高于TB组（P=0.026）。TB组IL-5水平明显低于健康对照组（P=0.005）。COPD组IL-5水平高于TB组（P=0.011）。COPD合并TB组以及TB组IL-6水平明显高于健康对照组（P=0.000）。COPD合并TB组IL-6水平明显高于TB组（P=0.035）。COPD合并TB组IL-6水平明显高于COPD组（P=0.000）。COPD合并TB组以及TB组TNF-ɑ水平明显高于健康对照组（P=0.000）。COPD合并TB组TNF-ɑ水平明显高于TB组（P=0.003）。COPD合并TB组TNF-ɑ水平明显高于COPD组（P=0.000）。COPD合并TB组以及TB组IFN-γ水平明显高于COPD组和健康对照组（P=0.000）。COPD合并TB组IFN-γ水平明显高于COPD组（P=0.000）。中重度肺结核患者血清中IL-6、TNF-ɑ、IFN-γ水平明显高于轻度患者（P＜0.05~0.01）。重度肺结核患者血清中sIL-2R、IL-6水平明显高于轻中度患者（P＜0.05~0.01）。单纯COPD轻中度患者血清中IL-6、TNF-ɑ水平与COPD患者FEV1预计值呈明显负相关性(P=0.000)。
结论：COPD合并TB患者血清某些细胞因子水平存在不同程度的失衡，提示其细胞免疫功能受到一定的损害，免疫受损的程度较单纯COPD和肺结核患者更为明显。同时表明，这些细胞因子在COPD合并肺结核的发生发展中起着重要作用。对COPD合并肺结核免疫功能的深入研究将进一步阐明其免疫发病机制，并为免疫干预治疗提供一定的理论依据。
Part Ⅰ Study on the humoral immunity function of patients with COPDcomplicated by TB
Objective：COPD patients are susceptible to TB. However, its pathogenesis has notbeen clearly demonstrated. Immune pathogenesis may participate in COPD complicated byTB. Yet, few studies were conducted, especially studies on the humoral immune functionof patients with COPD and TB. In this study, we measured the percentage of serum IgG,IgM and IgA in the patients with COPD and TB so as to understand humoral immunefunction and explore the immune pathogenesis of patients with COPD complicated by TB.
Methods：The humoral immune function of152cases of COPD complicated bypulmonary tuberculosis (COPD and TB group) was detected to compare with150cases ofpatients with pulmonary tuberculosis (TB group), as well as157cases of patients withCOPD (COPD group) and50cases of healthy volunteers (healthy control group) who werein the hospital during the same period (from January,2009to March,2012). The levelsof IgM, IgG and IgA were measured by immunoturbidimetry. The statistical results wereanalysed by SPSS15.0. The analysis was performed using the nonparametricKruskal-Wallis test to compare the immune parameters of TB with COPD patients, TBwithout COPD patients and healthy individuals, followed by the Mann-Whitney U test tocompare two TB groups. Correlations between different parameters were determined byspearman’s rank correlation coefficient. P values <0.05were considered significant.
Results: The study population consisted of152COPD complicated with TB patients,150TB patients,157COPD patients and50healthy volunteers. The level of IgG in the COPD with TB group was significantly higher than that in the COPD group (Z=-2.826,P=0.005). Meanwhile, the level of IgG in the TB group was significantly higher than thatin the COPD group (Z=-2.595, P=0.009). The level of IgA in COPD with TB group wassignificantly higher than that in the COPD group (Z=-3.377, P=0.001). The level of IgA inthe TB group was also significantly higher than that in the COPD group (Z=-3.640,P=0.000) and that in the control group (Z=-3.066, P=0.002).
Conclusions: The levels of IgG and IgA in patients with COPD complicated by TBare much higher. The increase of humoral immune response can play a protective role inpatients with COPD complicated by TB.
Part Ⅱ Change and its significance of T lymphocytes and NK cells inpatients with chronic obstructive pulmonary disease complicated bypulmonary tuberculosis
Objective: Both T lymphocytes and NK cells participate in the immune pathogenesisof TB complicated by COPD. However, the expression of these cells in patients withCOPD complicated by TB is still not clearly known. Thus, we measured the percentage ofT lymphocytes and NK cells in the patients with COPD and TB in order to explore thefunction and the significance of these immune cells in patients with chronic obstructivepulmonary disease (COPD) complicated by pulmonary tuberculosis.
Methods: The immune cells function of152cases of COPD complicated bypulmonary tuberculosis (COPD and TB group) was detected to compare with150cases ofpatients with pulmonary tuberculosis (TB group), as well as157cases of patients withCOPD (COPD group) and50cases of healthy volunteers (healthy control group) who werein the hospital during the same period (from January,2009to March,2012). Theexpression percentages of NK cells and T lymphocyte subsets in peripheral whole bloodsamples were detected by flow cytometry double-labeled antibody. The statistical resultswere analysed by SPSS15.0. The analysis was performed using the nonparametricKruskal-Wallis test to compare the immune parameters of TB with COPD patients, TB without COPD patients and healthy individuals, followed by the Mann-Whitney U test tocompare two TB groups. Correlations between different parameters were determined byspearman’s rank correlation coefficient. P values <0.05were considered significant.
Results: The study population consisted of152COPD complicated with TB patients,150TB patients,157COPD patients and50healthy volunteers. The percentage of CD4+Tcells in the COPD and TB group was significantly lower than that in the TB group(p≤0.001). The percentage of serum CD4+T cells in the TB group was much higher thanthat in the COPD and TB group (p=0.02). The CD4+/CD8+ratios in the COPD and TBgroup, TB group and COPD group were significantly lower than that in the control group(p=0.000). The percentage of serum NK cells in the TB group was significantly lower thanthe patients in other groups (p=0.000). There was no significantly statistical difference inthe percentage of serum NK cells between the COPD and TB group and the COPD group(p>0.05). There was no significantly statistical difference in the percentage of serum NKcells between the COPD and TB group and the control group (p>0.05) as well as betweenthe COPD group and the control group (p>0.05).
Conclusion: The percentage of serum CD4+T cells in the patients with COPD andTB was lower than that in the control group. So were the CD4+/CD8+ratio. Meanwhile,the percentage of serum CD8+T cells in the patients with COPD and TB was higher thanthat in the control group. This suggests that there be impaired cellular immunity in thepatients with COPD and TB. The decrease of the percentage of CD4+T cells and theCD4+/CD8+ratio as well as the increase in the percentage of CD8+T cells can be one ofthe important immune pathogenesis of COPD complicated by TB.
Part Ⅲ The change and its significance of cytokines in the patients withCOPD complicated with TB
Objective: Many cytokines participate in immune response and immune pathogenesisof TB and chronic obstructive pulmonary disease (COPD). However, the expression andcharacteristics as well as the immune pathogenesis of these cytokines in patients with COPD complicated with TB are not known. In the study, we measured the percentage ofserum cytokines in the patients with COPD and TB to explore the function and thesignificance of these cytokines in patients with COPD complicated by pulmonarytuberculosis.
Methods: The percentage of cytokines of152cases of COPD complicated bypulmonary tuberculosis (COPD and TB group) was detected to compare with150cases ofpatients with pulmonary tuberculosis (TB group), as well as157cases of patients withCOPD (COPD group) and50cases of healthy volunteers (healthy control group) who werein the hospital during the same period (from January,2009to March,2012). The cytokines(IL-1, IL-5, IL-5, sIL-2R, TNF-, IFN-γ) were measured by the enzyme-linkedimmunosorbent assay (ELISA). The statistical results were analysed by SPSS15.0. Theanalysis was performed using the nonparametric Kruskal-Wallis test to compare theimmune parameters of TB with COPD patients, TB without COPD patients and healthyindividuals, followed by the Mann-Whitney U test to compare two TB groups. Correlationsbetween different parameters were determined by spearman’s rank correlation coefficient.P values <0.05were considered significant.
Results: The study population consisted of152COPD complicated with TB patients,150TB patients,157COPD patients and50healthy volunteers. The percentage of IL-1inthe COPD and TB group was significantly lower than that in the control group (p=0.002).So was that in the TB group (p=0.003) and in the COPD group (p=0.000). The percentageof sIL-2R in the COPD and TB group and in the TB group were significantly higher thanthat in the control group (p=0.000). The percentage of sIL-2R in the COPD and TB groupwas significantly higher than that in the TB group (p=0.041). The percentage of sIL-2R inthe COPD and TB group was also higher than the percentage of sIL-2R of the COPDgroup (P=0.000).The percentage of IL-5in the COPD and TB group was significantlyhigher than that in the TB group (p=0.026). The percentage of IL-5in the TB group wasmuch lower than that in the control group (p=0.005). The percentage of IL-5in the COPDgroup was much lower than that in the TB group (p=0.011). The percentage of IL-6in the COPD and TB group as well as in the TB group was much higher than that in the controlgroup (p=0.000). The percentage of IL-6in the COPD and TB group was higher than thatin the TB group (p=0.035) and that in the COPD group (p=0.000). The percentage ofTNF-in the COPD and TB group as well as in the TB group was much higher than that inthe control group (p=0.000). The percentage of TNF-in the COPD and TB group washigher than that in the TB group (p=0.003) and that in in the COPD (p=0.000). As forIFN-γ, the percentage in the COPD and TB group as well as that in the TB group wasmuch higher than that in the control group (p=0.000). The percentage of IFN-γ in theCOPD and TB group was higher than that in the TB group (p=0.000). The serum levels ofIL-6, TNF-, IFN-γ in patients with moderate and advanced TB significantly increased ascompared to mild TB (p<0.05-0.01). The serum sIL-2R, IL-6levels of patients withadvanced TB were significant higher than those of patients with mild or moderate TB. Ofmeasured immune parameters, TNF-ɑ and IL-6showed negative significant correlationswith FEV1of predicted in patients with mild-moderate COPD without TB (P=0.000).
Conclusions: There are different extents of imbalance of some serum cytokines in thepatients with COPD complicated by TB. It suggests that there be impaired cellular immunefunction. The damage of cellular immune in patients with COPD complicated by TB maybe more significant than that in patients with COPD and the patients with TB. The studyalso showed important roles of these cytokines in immune pathogenesis of COPDcomplicated with TB. Further studies in immune function in patients with COPDcomplicated with TB can demonstrate its immune pathogenesis, which will providetheoretical evidence to immune intervention.
目的：慢性阻塞性肺疾病（COPD）易患结核病，然而，其确切机制尚未阐明。免疫机制可能参与了COPD伴发肺结核的发生与发展中，但相关研究很少，尤其是COPD合并肺结核患者体液免疫功能的研究更少。通过对COPD合并肺结核患者血清IgG、IgM和IgA的水平进行检测，了解其体液免疫功能状态，探讨COPD患者易患结核病的免疫发生机制。
方法：对2009年1月至2012年3月在上海市肺科医院的COPD合并肺结核患者（COPD合并TB组）、肺结核患者（TB组）以及COPD患者（COPD组）和正常健康人（健康对照组）的体液免疫功能进行对比分析。采用免疫比浊法检测各组血清中IgM、IgG、IgA含量。数据的结果应用SPSS15.0统计学软件(SPSS Inc., IL)进行分析。四组间的比较采用的是K个独立样本的非参数检验中的Kruskal-Wallis检验。两组间的比较采用的是两个独立样本的非参数检验中的Mann-Whitney U检验。不同参数的相关性通过Spearman’s等级相关系数来确定。P＜0.05为差异有统计学意义。
结果：该研究共入选152例COPD合并肺结核患者、157例COPD患者、150肺结核患者以及50例正常健康人。COPD合并TB组血清IgG水平明显高于COPD组，差异有统计学意义（Z=-2.826，P=0.005）。TB组血清IgG水平明显高于COPD组，差异有统计学意义（Z=-2.595，P=0.009）。COPD合并TB组IgA含量明显高于COPD组，差异有统计学意义（Z=-3.377，P=0.001）。COPD合并TB组IgA含量明显高于健康对照组，差异有统计学意义（Z=-2.955，P=0.003）。TB组IgA含量明显高于COPD组，差异有统计学意义（Z=-3.640，P=0.000）。TB组IgA含量明显高于健康对照组，差异有统计学意义（Z=-3.066，P=0.002）。
结论：COPD合并TB患者IgG和IgA水平均明显升高，这种增强的体液免疫应答在COPD并发肺结核发生过程中可能对机体起到一定的保护作用。
第二部分慢性阻塞性肺疾病合并肺结核患者T淋巴细胞及NK细胞的变化及其意义
目的：T淋巴细胞、自然杀伤（NK）细胞均参与了结核病及COPD的免疫发病过程。然而，这些细胞在COPD合并肺结核患者中的表达情况如何却知之甚少。为此，我们对COPD合并肺结核患者T淋巴细胞和NK细胞的水平进行检测，以探讨这些细胞在COPD合并结核病发生发展过程中的作用和意义。
方法：对2009年1月至2012年3月在上海市肺科医院的COPD合并肺结核患者（COPD合并TB组）、肺结核患者（TB组）以及COPD患者（COPD组）和正常健康人（健康对照组）的免疫细胞水平进行对比分析。采用流式细胞仪（BDAccuri C6）抗体双标法测定NK细胞及T淋巴细胞亚群及其比率。数据的结果应用SPSS15.0统计学软件(SPSS Inc., IL)进行分析。四组间的比较采用的是K个独立样本的非参数检验中的Kruskal-Wallis检验。两组间的比较采用的是两个独立样本的非参数检验中的Mann-Whitney U检验。不同参数的相关性通过Spearman’s等级相关系数来确定。P＜0.05为差异有统计学意义。
结果：该研究共入选152例COPD合并肺结核患者、157例COPD患者、150肺结核患者以及50例正常健康人。COPD合并TB组、TB组和COPD组血清CD4+T细胞比率均低于健康对照组，差异有统计学意义（P≤0.001）。TB组血清CD4+T细胞比率明显高于COPD合并TB组，差异有统计学意义（P=0.02）。COPD合并TB组、TB组和COPD组血清CD8+T细胞比率均高于健康对照组，差异有高度统计学意义（P=0.000）。COPD合并TB组、TB组和COPD组血清CD4+/CD8+T细胞比值均低于健康对照组，差异有统计学意义（P=0.000）。TB组血清NK细胞比率明显低于其他各组，差异有统计学意义（P=0.000）。COPD合并TB组和COPD组之间NK细胞比率差异也无统计学意义（P>0.05），COPD合并TB组和健康对照组之间NK细胞比率差异无统计学意义（P>0.05），COPD组和健康对照组之间NK细胞比率差异无统计学意义（P>0.05）。
结论：COPD合并TB患者血清CD4+T细胞比率、CD4+/CD8+T细胞比值均低于健康对照组， CD8+T细胞比率均高于健康对照组。表明，COPD合并肺结核患者细胞免疫功能受损。CD4+T细胞比率、CD4+/CD8+T细胞比值降低以及CD8+T细胞比率升高可能是其重要免疫发病机制之一。
第三部分慢性阻塞性肺疾病合并肺结核患者细胞因子的变化及其意义
目的：多种CK参与结核病及COPD的免疫应答及免疫发病过程。然而，这些细胞因子在COPD合并肺结核患者中的表达状态和特征如何却知之甚少。为此，我们对COPD合并肺结核患者血清细胞因子水平进行检测，以探讨这些细胞因子在COPD合并结核病发生发展过程中的作用和意义。
方法：对2009年1月至2012年3月在上海市肺科医院的COPD合并肺结核患者（COPD合并TB组）、肺结核患者（TB组）以及COPD患者（COPD组）和正常健康人（健康对照组）的细胞因子水平进行对比分析。采用双抗体夹心ELISA方法测定患者血清中IL-1、IL-5、IL-6、sIL-2R、TNF-、IFN-γ等细胞因子水平。数据的结果应用SPSS15.0统计学软件(SPSS Inc., IL)进行分析。四组间的比较采用的是K个独立样本的非参数检验中的Kruskal-Wallis检验。两组间的比较采用的是两个独立样本的非参数检验中的Mann-Whitney U检验。不同参数的相关性通过Spearman’s等级相关系数来确定。P＜0.05为差异有统计学意义。
结果：该研究共入选152例COPD合并肺结核患者、157例COPD患者、150肺结核患者以及50例正常健康人。COPD合并TB组IL-1水平明显低于健康对照组，差异有统计学意义（P=0.002）。TB组IL-1水平明显低于健康对照组（P=0.003）。COPD组IL-1水平明显低于健康对照组（P=0.000）。COPD合并TB组以及TB组sIL-2R水平均明显高于健康对照组（P=0.000）。COPD合并TB组sIL-2R水平明显高于TB组（P=0.041）。COPD合并TB组sIL-2R水平明显高于COPD组（P=0.000）。COPD合并TB组IL-5水平明显高于TB组（P=0.026）。TB组IL-5水平明显低于健康对照组（P=0.005）。COPD组IL-5水平高于TB组（P=0.011）。COPD合并TB组以及TB组IL-6水平明显高于健康对照组（P=0.000）。COPD合并TB组IL-6水平明显高于TB组（P=0.035）。COPD合并TB组IL-6水平明显高于COPD组（P=0.000）。COPD合并TB组以及TB组TNF-ɑ水平明显高于健康对照组（P=0.000）。COPD合并TB组TNF-ɑ水平明显高于TB组（P=0.003）。COPD合并TB组TNF-ɑ水平明显高于COPD组（P=0.000）。COPD合并TB组以及TB组IFN-γ水平明显高于COPD组和健康对照组（P=0.000）。COPD合并TB组IFN-γ水平明显高于COPD组（P=0.000）。中重度肺结核患者血清中IL-6、TNF-ɑ、IFN-γ水平明显高于轻度患者（P＜0.05~0.01）。重度肺结核患者血清中sIL-2R、IL-6水平明显高于轻中度患者（P＜0.05~0.01）。单纯COPD轻中度患者血清中IL-6、TNF-ɑ水平与COPD患者FEV1预计值呈明显负相关性(P=0.000)。
结论：COPD合并TB患者血清某些细胞因子水平存在不同程度的失衡，提示其细胞免疫功能受到一定的损害，免疫受损的程度较单纯COPD和肺结核患者更为明显。同时表明，这些细胞因子在COPD合并肺结核的发生发展中起着重要作用。对COPD合并肺结核免疫功能的深入研究将进一步阐明其免疫发病机制，并为免疫干预治疗提供一定的理论依据。
Part Ⅰ Study on the humoral immunity function of patients with COPDcomplicated by TB
Objective：COPD patients are susceptible to TB. However, its pathogenesis has notbeen clearly demonstrated. Immune pathogenesis may participate in COPD complicated byTB. Yet, few studies were conducted, especially studies on the humoral immune functionof patients with COPD and TB. In this study, we measured the percentage of serum IgG,IgM and IgA in the patients with COPD and TB so as to understand humoral immunefunction and explore the immune pathogenesis of patients with COPD complicated by TB.
Methods：The humoral immune function of152cases of COPD complicated bypulmonary tuberculosis (COPD and TB group) was detected to compare with150cases ofpatients with pulmonary tuberculosis (TB group), as well as157cases of patients withCOPD (COPD group) and50cases of healthy volunteers (healthy control group) who werein the hospital during the same period (from January,2009to March,2012). The levelsof IgM, IgG and IgA were measured by immunoturbidimetry. The statistical results wereanalysed by SPSS15.0. The analysis was performed using the nonparametricKruskal-Wallis test to compare the immune parameters of TB with COPD patients, TBwithout COPD patients and healthy individuals, followed by the Mann-Whitney U test tocompare two TB groups. Correlations between different parameters were determined byspearman’s rank correlation coefficient. P values <0.05were considered significant.
Results: The study population consisted of152COPD complicated with TB patients,150TB patients,157COPD patients and50healthy volunteers. The level of IgG in the COPD with TB group was significantly higher than that in the COPD group (Z=-2.826,P=0.005). Meanwhile, the level of IgG in the TB group was significantly higher than thatin the COPD group (Z=-2.595, P=0.009). The level of IgA in COPD with TB group wassignificantly higher than that in the COPD group (Z=-3.377, P=0.001). The level of IgA inthe TB group was also significantly higher than that in the COPD group (Z=-3.640,P=0.000) and that in the control group (Z=-3.066, P=0.002).
Conclusions: The levels of IgG and IgA in patients with COPD complicated by TBare much higher. The increase of humoral immune response can play a protective role inpatients with COPD complicated by TB.
Part Ⅱ Change and its significance of T lymphocytes and NK cells inpatients with chronic obstructive pulmonary disease complicated bypulmonary tuberculosis
Objective: Both T lymphocytes and NK cells participate in the immune pathogenesisof TB complicated by COPD. However, the expression of these cells in patients withCOPD complicated by TB is still not clearly known. Thus, we measured the percentage ofT lymphocytes and NK cells in the patients with COPD and TB in order to explore thefunction and the significance of these immune cells in patients with chronic obstructivepulmonary disease (COPD) complicated by pulmonary tuberculosis.
Methods: The immune cells function of152cases of COPD complicated bypulmonary tuberculosis (COPD and TB group) was detected to compare with150cases ofpatients with pulmonary tuberculosis (TB group), as well as157cases of patients withCOPD (COPD group) and50cases of healthy volunteers (healthy control group) who werein the hospital during the same period (from January,2009to March,2012). Theexpression percentages of NK cells and T lymphocyte subsets in peripheral whole bloodsamples were detected by flow cytometry double-labeled antibody. The statistical resultswere analysed by SPSS15.0. The analysis was performed using the nonparametricKruskal-Wallis test to compare the immune parameters of TB with COPD patients, TB without COPD patients and healthy individuals, followed by the Mann-Whitney U test tocompare two TB groups. Correlations between different parameters were determined byspearman’s rank correlation coefficient. P values <0.05were considered significant.
Results: The study population consisted of152COPD complicated with TB patients,150TB patients,157COPD patients and50healthy volunteers. The percentage of CD4+Tcells in the COPD and TB group was significantly lower than that in the TB group(p≤0.001). The percentage of serum CD4+T cells in the TB group was much higher thanthat in the COPD and TB group (p=0.02). The CD4+/CD8+ratios in the COPD and TBgroup, TB group and COPD group were significantly lower than that in the control group(p=0.000). The percentage of serum NK cells in the TB group was significantly lower thanthe patients in other groups (p=0.000). There was no significantly statistical difference inthe percentage of serum NK cells between the COPD and TB group and the COPD group(p>0.05). There was no significantly statistical difference in the percentage of serum NKcells between the COPD and TB group and the control group (p>0.05) as well as betweenthe COPD group and the control group (p>0.05).
Conclusion: The percentage of serum CD4+T cells in the patients with COPD andTB was lower than that in the control group. So were the CD4+/CD8+ratio. Meanwhile,the percentage of serum CD8+T cells in the patients with COPD and TB was higher thanthat in the control group. This suggests that there be impaired cellular immunity in thepatients with COPD and TB. The decrease of the percentage of CD4+T cells and theCD4+/CD8+ratio as well as the increase in the percentage of CD8+T cells can be one ofthe important immune pathogenesis of COPD complicated by TB.
Part Ⅲ The change and its significance of cytokines in the patients withCOPD complicated with TB
Objective: Many cytokines participate in immune response and immune pathogenesisof TB and chronic obstructive pulmonary disease (COPD). However, the expression andcharacteristics as well as the immune pathogenesis of these cytokines in patients with COPD complicated with TB are not known. In the study, we measured the percentage ofserum cytokines in the patients with COPD and TB to explore the function and thesignificance of these cytokines in patients with COPD complicated by pulmonarytuberculosis.
Methods: The percentage of cytokines of152cases of COPD complicated bypulmonary tuberculosis (COPD and TB group) was detected to compare with150cases ofpatients with pulmonary tuberculosis (TB group), as well as157cases of patients withCOPD (COPD group) and50cases of healthy volunteers (healthy control group) who werein the hospital during the same period (from January,2009to March,2012). The cytokines(IL-1, IL-5, IL-5, sIL-2R, TNF-, IFN-γ) were measured by the enzyme-linkedimmunosorbent assay (ELISA). The statistical results were analysed by SPSS15.0. Theanalysis was performed using the nonparametric Kruskal-Wallis test to compare theimmune parameters of TB with COPD patients, TB without COPD patients and healthyindividuals, followed by the Mann-Whitney U test to compare two TB groups. Correlationsbetween different parameters were determined by spearman’s rank correlation coefficient.P values <0.05were considered significant.
Results: The study population consisted of152COPD complicated with TB patients,150TB patients,157COPD patients and50healthy volunteers. The percentage of IL-1inthe COPD and TB group was significantly lower than that in the control group (p=0.002).So was that in the TB group (p=0.003) and in the COPD group (p=0.000). The percentageof sIL-2R in the COPD and TB group and in the TB group were significantly higher thanthat in the control group (p=0.000). The percentage of sIL-2R in the COPD and TB groupwas significantly higher than that in the TB group (p=0.041). The percentage of sIL-2R inthe COPD and TB group was also higher than the percentage of sIL-2R of the COPDgroup (P=0.000).The percentage of IL-5in the COPD and TB group was significantlyhigher than that in the TB group (p=0.026). The percentage of IL-5in the TB group wasmuch lower than that in the control group (p=0.005). The percentage of IL-5in the COPDgroup was much lower than that in the TB group (p=0.011). The percentage of IL-6in the COPD and TB group as well as in the TB group was much higher than that in the controlgroup (p=0.000). The percentage of IL-6in the COPD and TB group was higher than thatin the TB group (p=0.035) and that in the COPD group (p=0.000). The percentage ofTNF-in the COPD and TB group as well as in the TB group was much higher than that inthe control group (p=0.000). The percentage of TNF-in the COPD and TB group washigher than that in the TB group (p=0.003) and that in in the COPD (p=0.000). As forIFN-γ, the percentage in the COPD and TB group as well as that in the TB group wasmuch higher than that in the control group (p=0.000). The percentage of IFN-γ in theCOPD and TB group was higher than that in the TB group (p=0.000). The serum levels ofIL-6, TNF-, IFN-γ in patients with moderate and advanced TB significantly increased ascompared to mild TB (p<0.05-0.01). The serum sIL-2R, IL-6levels of patients withadvanced TB were significant higher than those of patients with mild or moderate TB. Ofmeasured immune parameters, TNF-ɑ and IL-6showed negative significant correlationswith FEV1of predicted in patients with mild-moderate COPD without TB (P=0.000).
Conclusions: There are different extents of imbalance of some serum cytokines in thepatients with COPD complicated by TB. It suggests that there be impaired cellular immunefunction. The damage of cellular immune in patients with COPD complicated by TB maybe more significant than that in patients with COPD and the patients with TB. The studyalso showed important roles of these cytokines in immune pathogenesis of COPDcomplicated with TB. Further studies in immune function in patients with COPDcomplicated with TB can demonstrate its immune pathogenesis, which will providetheoretical evidence to immune intervention.
引文
[1]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南（2013修订版）.中华结核和呼吸杂志，2013,36（4）：255-264.
[2] GOLD Executive Committee. Global strategy for the diagnosis,management,andprevention of chronic obstructive pulmonary disease(Revised2011)[EB/OL].[2012-01-16].http://www.goldcopd.com
[3] Calverley PM, Walker P.Chronic obstructive pulmonary disease. Lancet,2003,362:1053–1061.
[4] WHO. Global tuberculosis report2013. WHO/HTM/TB/2013.11. Geneva,Switzerland: WHO,2013.
[5] WHO. Global tuberculosis report2012. WHO/HTM/TB/2012.6. Geneva, Switzerland:WHO,2012.
[6]全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调查报告.中华结核和呼吸杂志，2002，25(1):3-7.
[7]全国第五次结核病流行病学抽样调查技术指导组.2010年全国第五次结核病流行病学抽样调查报告.中国防痨杂志，2012，34（8）：485-508.
[8]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[9]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[10]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30:707-708.
[11] Inghammar M, Ekbom A, Engstr m G, et al. COPD and the Risk of Tuberculosis-APopulation-Based Cohort Study. PLoSONE2010,5(4): e10138.
[12] Liu CH, Yang N, Wang Q, et al.(), Risk factors associated withfluoroquinolone-resistant tuberculosis in a Beijing tuberculosis referral hospital.Respirology,2011,16:918–925.
[13]郑立学，胡忠义.结核病体液免疫检测进展.临床肺科杂志，2000,5(2):86-88.
[14] Abebe F, Bjune G. The protective role of antibody responses during Mycobacteriumtuberculosis infection. The Journal of Translational Immunology,2009,157:235-243.
[15] de Valliere S, Abate G Blazevic A et al. Enhancement of cellmediated immunity byantimycobacterial antibodies. Infect Immun2005;73:6711-20.
[16] Relijic R, Ivanyi J. A case for passive immunoprophylaxis against tuberculosis.Lancet Infect Dis2006;6:813-18.
[17] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[18] Brandsma CA, Kerstjens HA, van Geffen WH, et al. Differential switching to IgG andIgA in active smoking COPD patients and healthy controls. Eur Respir J,2012,40(2):313-321.
[19] Feghali-Bostwick CA, Gadgil AS, Otterbein LE, et al. Autoantibodies in Patientswith Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med,2008:177(2):156-163.
[20]朱友生，唐神结.巨噬细胞在抗结核免疫中的作用及其研究进展.中国防痨杂志，2004，26（3）：173-175.
[21]唐神结，肖和平.细胞因子网络与结核病.中华结核和呼吸杂志2001，24（9）：571-574.
[22] Shirai T, Suda T, Inui N. Correlation between peripheral blood T-cell profilesand clinical and inflammatory parameters in stable COPD. Allergol Int,2010,59(1):75-82.
[23] Shenjie Tang, Haiyan Cui, Lan Yao,et al. Increased Cytokines Response in Patientswith Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease. PLOSONE,2013,8(4):e62385.
[24] Zahran WA，Ghonaim MM, Koura BA, et al. Human natural killer T cells(NKT),NKand T cells in pulmonary tuberculosis:potential indicators for disease activity andprognosis. Egypt J Immunol.2006,13(1):67-78.
[25] Kulpraneet M, Sukwit S, Sumransurp K, et al. Cytokine production in NK and NKTcells from Mycobacterium tuberculosis infected patients. Southeast Asian J Trop MedPublic Health,2007,38(2):370-375.
[26]翟慧,刘一典,唐神结,等.肺结核患者外周血NKT细胞、NK细胞、T淋巴细胞亚群的变化及意义.同济大学学报(医学版),2010;31(5):42-46.
[27]张蔚，江山平，吕志强，等.慢性阻塞性肺疾病患者外周血T淋巴细胞亚群和NK细胞的动态变化.中山大学学报（医学科学版），2005，3S：115-116.
[28] Mueller H, Detjen AK, Schuck SD, et al. Mycobacterium tuberculosis-specific CD4+,IFNgamma+, and TNFalpha+multifunctional memory T cells coexpress GM-CSF.Cytokine,2008,43(2):143-148.
[29] Küpeli E, Karnak D, Beder S, et al. Diagnostic accuracy of cytokine levels(TNF-alpha, IL-2and IFN-gamma) in bronchoalveolar lavage fluid of smear-negativepulmonary tuberculosis patients. Respiration,2008,75(1):73-78.
[30] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scand JImmunol,2012,75(6):623-632.
[31] Shitrit D, Izbicki G, Bar-Gil Shitrit A, et al. Role of soluble interleukin-2receptorlevels in patients with latent tuberculosis. Lung,2006,184(1):21-24.
[32] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease. Am JRespir Cell Mol Biol,2009,41:631–638.
[33] GadgilA, Zhu X, Sciurba FC, et al. Altered T-cell phenotypes in chronic obstructivepulmonary disease. Proc Am Thorac Soc,2006,3(6):487-488.
[1] Calverley PM, Walker P.Chronic obstructive pulmonary disease. Lancet,2003,362:1053–1061.
[2] WHO. Global tuberculosis report2013. WHO/HTM/TB/2013.11. Geneva,Switzerland: WHO,2013.
[3] WHO. Global tuberculosis report2012. WHO/HTM/TB/2012.6. Geneva, Switzerland:WHO,2012.
[4]全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调查报告.中华结核和呼吸杂志，2002，25(1):3-7.
[5]全国第五次结核病流行病学抽样调查技术指导组.2010年全国第五次结核病流行病学抽样调查报告.中国防痨杂志，2012，34（8）：485-508.
[6]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[7]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[8]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30：.707-708.
[9] Inghammar M, Ekbom A, Engstr m G, et al. COPD and the Risk of Tuberculosis-APopulation-Based Cohort Study. PLoSONE2010,5(4): e10138.
[10] Liu CH, Yang N, Wang Q, et al. Risk factors associated with fluoroquinolone-resistanttuberculosis in a Beijing tuberculosis referral hospital. Respirology,2011,16:918–925.
[11]郑立学，胡忠义.结核病体液免疫检测进展.临床肺科杂志，2000,5(2):86-88.
[12]黄奕江,冯夏,郑万川.慢性阻塞性肺疾病患者免疫功能研究.临床内科杂志,1997,14(1):30.
[13]吴纪珍，张罗献，马利军，等。老年慢性阻塞性肺疾病患者免疫功能测定及其意义。医药论坛杂志，25（23）：10-12。
[14] Musher DM, Groover JE, Rowand JM, et al. Antibody to capsular polysaccharides ofstreptococcus pneumoniae: prevalence, persistence, and response to revaccination.Clin lnfect Dis,1993,17(3):66-73.
[15] Ghimire Hridaya, Li Jian. Role of Latent Tuberculosis Infection in the Pathogenesisand Severity of COPD. Chest.2011,140（4_Meeting Abstracts）:564A.
[16] Ernst P, Suissa S. Systemic effects of inhaled corticosteroids. Curr Opin Pulm Med.2012,18(1):85-89.
[17] Shu CC, Wu HD, Yu MC. Use of High-Dose Inhaled Corticosteroids is AssociatedWith Pulmonary Tuberculosis in Patients With Chronic Obstructive PulmonaryDisease. Medicine.2010,89(1):53-61.
[18]中华医学会.临床诊疗指南（结核病分册）［M］.北京：人民卫生出版社，2005：64-86.
[19] GOLD. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. http://www.goldcopd.com.2010:1–91.
[20]王巍，王安生。结核病细胞免疫和体液免疫研究的若干研究。中国防痨杂志，1997，19（4）：197-200。
[21] Maglione PJ, Chan J. How B cells shape the immune response againstMycobacterium tuberculosis. European Journal of Immunology,2009,39:676-686.
[22] Abebe F, Bjune G. The protective role of antibody responses during Mycobacteriumtuberculosis infection. The Journal of Translational Immunology,2009,157:235-243.
[23] de Valliere S, Abate G, Blazevic A, et al. Enhancement of cellmediated immunity byantimycobacterial antibodies. Infect Immun2005;73:6711-20.
[24] Relijic R, Ivanyi J. A case for passive immunoprophylaxis against tuberculosis.Lancet Infect Dis2006;6:813-18.
[25] Pethe K, Alonso S, Biet F et al. The heparin-binding hemagglutinin of M. tuberculosisis required for extrapulmonary dissemination.Nature2001;412:190-4.
[26] Chambers MA, Gavier-Widen D, Hewinson RG. Antibody bound to the surfaceantigen MPB83of Mycobacterium bovis enhances survival against high dose and lowdose challenge. FEMS Immunol Med Microbiol2004;41:93-100.
[27] Shen CY, Hsieh SC, Yu CL, et al. Autoantibody prevalence in active tuberculosis:reactive or pathognomonic? BMJ Open,2013,3(7): pii: e002665.
[28] Boes M. Role of natural and immune IgM antibodies in immune responses. MolImmunol,2000,37:1141-1149.
[29]周世明,贾杰,杨建国.乌体林斯治疗肺结核前后免疫功能的改变济临床意义.中国热带医学杂志,2003,3(5):623.
[30]韩庆,王怀诚.观察人体胎盘脂多糖辅助治疗初治菌阳肺结核疗效及安全性.江苏医药,2006,32(12):1191.
[31]何菊芳，佟爱华，董梅，等.肺结核患者血清蛋白电泳图谱与体液免疫水平相关性的探讨.中国实验诊断学，2011，15（10）：1742-1743.
[32] Le Moigne V, Le Moigne D, Mahana W. Antibody response to Mycobacteriumtuberculosis p27-PPE36antigen in sera of pulmonary tuberculosis patients.Tuberculosis,2013,93(2):189-191.
[33] Glatman-Freedman A. The role of antibody-mediated immunity in defense againstMycobacterium tuberculosis: advances toward a novel vaccine strategy. Tuberculosis(Edinb)2006,86:191-97.
[34] Reljic R. Clark SO, Williams A, et al. Intranasal IFNgamma extends passive IgAantibody protection of mice against Mycobacterium tuberculosis lung infection. ClinExp Immunol,2006,143:467-473.
[35] Hamasur B, Haile M, Pawlowski A, et al. A mycobacterial lipoarabinomannanspecific monoclonal antibody and its F(ab0) fragment prolong survival of miceinfected with Mycobacterium tuberculosis. Clin Exp Immunol,2004,138:30-38.
[36] Williams A, Reljic R, Naylor I, et al. Passive protection with immunoglobulin Aantibodies against tuberculous early infection of the lungs. Immunology,2004,111:328-333.
[37] Mattos AM,Almeida CdeS, Franken KL, et al. Increased IgG1, IFN-gamma,TNF-alpha and IL-6responses to Mycobacterium tuberculosis antigens in patientswith tuberculosis are lower after chemotherapy. International Immunology,2010,22(9):775-782.
[38]佟玉平，李艳丽和张春梅.肺结核病人应用肺活素治疗前后的细胞因子及体液免疫水平检测.黑龙江医学，2008，28（5）：377.
[39] Zu iga J, Torres-García D, Santos-Mendoza T, et al. Cellular and humoralmechanisms involved in the control of tuberculosis. Clinical and developmentalImmunology,2012,2012:193923.
[40] Costello DAM, Kumar A, Narayan V et al.“Does antibody to mycobacterial antigens,including lipoarabinomannan, limit dissemination in childhood tuberculosis?”Transactions of the Royal Society of Tropical Medicine and Hygiene,1992,86(6):686-692.
[41] da Costa CTKA, Khanolkar-Young S, Elliott AM, et al.“Immunoglobulin G subclassresponses tomycobacterial lipoarabinomannan in HIV-infected and non-infectedpatients with tuberculosis,” Clinical and Experimental Immunology,1993,91(1):25-29.
[42]匡铁吉，宋萍，金关甫，等.住院肺结核患者体液免疫水平的变化及其临床意义.军医进修学院学报，1996，17（3）：178-181.
[43]尹洪云,徐家琏.慢性阻塞性肺疾病与肺结核的关系.中国临床医生，2004，32(8)：12-14.
[44] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[45]朱渊红,王新华,王真,等.60例慢性阻塞性肺疾病细胞免疫功能的临床观察.浙江实用医学,2005,10（5）:321-322.
[46]黄琛，胡轶，汤汉红.COPD患者肺功能与血清免疫球蛋白及C反应蛋白的关系.医学新知杂志，2008，18（2）：111-112.
[47] Feghali-Bostwick CA, Gadgil AS, Otterbein LE,et al. Autoantibodies in Patients withChronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med,2008:177(2):156-163.
[48] Brandsma CA, Kerstjens HA, van Geffen WH, et al. Differential switching to IgG andIgA in active smoking COPD patients and healthy controls. Eur Respir J,2012,40(2):313-321.
[49] Brandsma C, Hylkema MN, Geerlings M, et al. Increased levels of (class switched)memory B cells in peripheral blood of current smokers. RespiratoryResearch,2009,10:108-118.
[50] Millares L, Marin A, Garcia-Aymerich J, et al. Specific IgA and metalloproteinaseactivity in bronchial secretions from stable chronic obstructive pulmonary diseasepatients colonized by Haemophilus influenza. Respiratory Research,2012,13:113-123.
[51]沈芸，唐神结，孙华，郝晓晖．肺结核合并慢性阻塞性肺疾病患者免疫功能的变化及意义．同济大学学报（医学版）．2012，33（1）：53-58．
[1]朱友生，唐神结.巨噬细胞在抗结核免疫中的作用及其研究进展.中国防痨杂志，2004，26（3）：173-175.
[2]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[3]唐神结，肖和平.细胞因子网络与结核病.中华结核和呼吸杂志2001，24（9）：571-574.
[4] Zahran WA，Ghonaim MM, Koura BA, et al. Human natural killer T cells(NKT),NKand T cells in pulmonary tuberculosis:potential indicators for disease activity andprognosis. Egypt J Immunol.2006,13(1):67-78.
[5] Kulpraneet M, Sukwit S, Sumransurp K, et al. Cytokine production in NK and NKTcells from Mycobacterium tuberculosis infected patients. Southeast Asian J Trop MedPublic Health,2007,38(2):370-375.
[6] Vankayalapati R, Klucar P, Wizel B, et al. NK cells regulate CD8+Tcell effectorfunction in response to an intracellular pathogen. J Immunol,2004,172:130-137.
[7] Schierloh P, Yokobori N, Aleman M, et al. Mycobacterium tuberculosis-InducedGamma Interferon Production by Natural Killer Cells Requires Cross Talk withAntigen-Presenting Cells Involving Toll-Like Receptors2and4and the MannoseReceptor in Tuberculous Pleurisy.Infect and Immun,2007,75(11):5325-5337.
[8] Nirmala R, Narayanan PR, Mathew R, et al. Reduced NK activity in pulmonarytuberculosis patients with/without HIV infection: identifying the defective stage andstudying the effect of interleukins on NK activity.Tuberculosis,2001,81（5-6）:343-352.
[9] Deveci F， Akbulut HH， Celik I. Lymphocyte subpopulations in pulmonarytuberculosis patients.Mediators Inflamm,2006，2006(2):89070.
[10] Yildiz P, Kadakal F, Tutuncu Y, et al. Natural killer cell activity in multidrug-resistantpulmonary tuberculosis. Respiration,2001,68（6）:590-594.
[11] Kim W D, Kim W S, Koh Y. Abnormal peripheral blood T-lymphocytesubsets in a subgroup of patients with COPD. Chest.,2002,122(2):437-444.
[12] Shirai T, Suda T, Inui N. Correlation between peripheral blood T-cell profilesand clinical and inflammatory parameters in stable COPD. Allergol Int,2010,59(1):75-82.
[13] Glader P, von Wachenfeldt K, et al. Systemic CD4+T-cell activation is correlated with FEV1insmoker. Respir Med2006,100(6):1088-1093.
[14] Majo J， Ghezzo H， Cosio MG． Lymphocyte population and apoptosis in the lungs of smokersand their relation to emphysema． Eur Respir J,2001,17：946-953．
[15]崔微艳，陆洁，邹静蓉，等．慢性阻塞性肺疾病患者外周血T细胞亚群分析.岭南急诊医学杂志，2008，13（6）:414-415.
[16]汤其岭．COPD患者治疗前后血清SOD和T淋巴细胞亚群检测的临床意义．淮海医药，2008，26（6）：486-487．
[17]夏晓东，刘道候，徐永安，等.慢性阻塞性肺疾病患者T细胞亚群动态变化.浙江实用医学，2008,13（2）:85-86.
[18]黄美健，冷报浪，梁斌，等.慢性阻塞性肺疾病不同病期细胞免疫功能的临床研究.浙江实用医学,2004,6（8）:664-665.
[19]傅佩芳，殷少军，颜正茂，等。慢性阻塞性肺疾病患者与免疫功能关系的临床研究。中国现代医学杂志，2008，18（3）：338-340.
[20]王娜，夏婧.慢性阻塞性肺疾病患者免疫功能的变化.贵州医药，2011，35（7）:593-595.
[21]中华医学会.临床诊疗指南（结核病分册）［M］.北京：人民卫生出版社，2005：64-86.
[22] GOLD. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. http://www.goldcopd.com.2010:1–91.
[23] Chen CY, Huang D, Wang RC, et al. A critical role for CD8T cells in a nonhumanprimate model of tuberculosis. PLoS Pathogens,2009,5:e1000392.
[24] Elvang T, Christensen JP, Billeskov R, et al. CD4and CD8T cell responses to the M.tuberculosis Ag85B-TB10.4promoted by adjuvanted subunit, adenovector orheterologous prime boost vaccination.PLoS One,2009;4(4):e5139.
[25] Kiran B, Cagatay T, Clark P, et al. Can immune parameters be used as predictors todistinguish between pulmonary multidrug-resistant and drug-sensitive tuberculosis?Arch Med Sci,2010,6(1):77-82.
[26]杨妍，唐神结，张青，等.耐多药和广泛耐药肺结核患者外周血中免疫细胞的表达及其意义.中华结核和呼吸杂志,2011,34（2）:109-113.
[27]翟慧,刘一典,唐神结,等.肺结核患者外周血NKT细胞、NK细胞、T淋巴细胞亚群的变化及意义.同济大学学报(医学版),2010;31(5):42-46.
[28] Caccamo N, Guggino G, Joosten SA, et al. Multifunctional CD4(+) T cells correlate with activeMycobacterium tuberculosis infection. European Journal of Immunology,2010,40(8):2211-2220.
[29] Koch A, Gaczkowski M, Sturton G et al. Modification of surface antigens in bloodCD8+T-lymphocytes in COPD: effects of smoking. Eur Respir J,2007,29(1):42-50.
[30]张蔚，江山平，吕志强，等。慢性阻塞性肺疾病患者外周血T淋巴细胞亚群和NK细胞的动态变化。中山大学学报（医学科学版），2005，3S：115-116
[31] Kim WD, Kim WS, Koh Y, et al. Abnormal peripheral blood T-lymphocyte subsets ina subgroup of patients with COPD. Chest,2002,122(2):437-444.
[32] Chen C, Shen Y, Ni CJ, et al. Imbalance of Circulating T-Lymphocyte Subpopulationin COPD and its Relationship with CAT Performance. Journal of Clinical LaboratoryAnalysis,2012,26(2):109-114.
[33] Paats MS, Bergen IM, Hoogsteden HC, et al. Systemic CD4+and CD8+T-cellcytokine profiles correlate with GOLD stage in stable COPD. Eur RespirJ,2012,40(2):330-7.
[34] Domaga a-Kulawik J, Hoser G, Dabrowska M, et al. Increased proportion of Faspositive CD8+cells in peripheral blood of patients with COPD. Respiratory Medicine,2007,101(6):1338-1343.
[35] L fdahl MJ, Roos-Engstrand E, Pourazar J, et al. Increased intraepithelial T-cells instable COPD. Respiratory Medicine,2008,102(12):1812-1818.
[36] Malin Inghammar M, Anders Ekbom A, Engstr m G, et al. COPD and the Risk ofTuberculosis-A Population-Based Cohort Study. PLoS One,2010,5(4): e10138.
[37] Leung WL, Law KL, Leung VS et al. Comparison of intracellular cytokine flowcytometry and an enzyme immunoassay for evaluat ion of cellularimmune response toactive tuberculosis. Clin Vaccine Immunol,2009;16(3):344-351.
[38]孙巍，杨永辉，李登瑞，等.NKT细胞、NK细胞和T细胞亚群在活动性肺结核患者外周血的表达及意义.中国免疫杂志，2011，27（11）：1030-1034.
[39]张青，肖和平． T细胞、NKT细胞和NK细胞在结核病诊断中的意义探讨．中国防痨杂志，2010，32(5):267-271．
[40]邱晓静，王兆华，王健，等.肺结核患者外周血NK细胞数量和胞内杀伤分子的变化.蚌埠医学院学报，2012，37（10）：1141-1144.
[41]周晓映，于红艳，王惠青，等.2型糖尿病合并肺结核患者T淋巴细胞亚群和NK细胞的变化及其临床意义.疑难病杂志，2008，7（11）：666-668.
[42]王心静，杨秉芬，原艳明，等.初治菌阳肺结核患者外周血NK细胞比例显著下降.免疫学杂志，2013，29（8）：677-680.
[43] Portevin D, Via LE, Eum S, et al. Natural killer cells are recruited during pulmonarytuberculosis and their ex vivo responses to mycobacteria vary between healthy humandonors in association with KIR haplotype. Cell Microbiol,2012,14(11):1734-1744.
[44] Vankayalapati R, Wizel B, Weis SE, et al. The NKp46receptor contributes to NKcell lysis of mononuclear phagocytes infected with an intracellular bacterium. JImmunol,2002,168(7):3451-3457.
[45]付笑迎,李丽,李琴,等.结核性胸液中NK细胞的亚群及表型功能特征分析.免疫学杂志,2012,28(8):691-694.
[1]唐神结，肖和平.细胞因子网络与结核病.中华结核与呼吸杂志，2001,24（9）571-574.
[2] Sutherland JS, Garba D, Fombah AE et al. Highly accurate diagnosis of pleuraltuberculosis by immunological analysis of the pleural effusion. Plos One.2012;7(1):e30324.
[3] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scandinavian Journalof Immunology,2012,75(6):623-632.
[4]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[5]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30：.707-708.
[6]李红，唐神结.肺结核患者外周血sIL-2R、TNF-、IFN-γ、IL-6的检测及意义.中国防痨杂志，2011，33（1）：57-60.
[7]杨妍，唐神结，张青，等.耐多药和广泛耐药肺结核患者外周血中免疫细胞的表达及其意义.中华结核和呼吸杂志,2011,34（2）:109-113.
[8]唐神结，肖和平，范以虎，等.肺结核患者支气管肺泡灌洗液中某些细胞因子和受体的检测及其临床意义.中华传染病杂志，2009，27（3）：167-171.
[9] Katti MK. Assessment of serum IL-1, IL-2and IFN-γ levels in untreated pulmonarytuberculosis patients: role in pathogenesis. Archives of Medical Research,2011,42(3):199-201.
[10] Nemeth J, Winkler HM, Boeck L, et al. Specific cytokine patterns of pulmonarytuberculosis in Central Africa. Clinical Immunology.2011,138(1):50-59.
[11] Cui HY, Zhang Q, Su B, et al. Differential levels of cytokines and soluble Fas ligandbetween tuberculous and malignant effusions. The Journal of International Research,2010,38(6):2063-2069.
[12] Agusti A,Soriano JB.COPD as a systemic disease.COPD,2008,5(2):133-138.
[13] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease.American Journal of Respiratory Cell and Molecular Biology,2009,41:631-638.
[14] Kent L, Smyth L, Clayton C, et al. Cigarette smoke extract induced cytokine andchemokine gene expression changes in COPD macrophages.Cytokine,2008,42(2):205-216.
[15] Pinto-Plata VM, Livnat G, Girish M, et al. Systemic cytokines， clinical andphysiological changes in patients hospitalized for exacerbation ofCOPD.Chest,2007,131(1):37-43.
[16] Bathoorn E, Liesker JJ, Postma DS, et al.COPD patients from stable phase to a subsequent exacerbation. Int J Chron ObstructPulmon Dis,2009,4(1):101-109.
[17] Hacievliyagil SS, Gunen H, Mutlu LC, et al. Association between cytokines ininduced sputum and severity of chronic obstructive pulmonary disease. RespirMed,2006,100(5):846-854.
[18]吴纪珍，张罗献，马利军，等.老年慢性阻塞性肺疾病患者免疫功能测定及其意义。医药论坛杂志，2004，25（23）：10-12.
[19] Moermans C, Heinen V, Nguyen M, et al. Local and systemic cellular inflammationand cytokine release in chronic obstructive pulmonary disease. Cytokine,2011,56(2):298-304.
[20]孙雯雯，李燕芹，刘斌，等.慢性阻塞性肺疾病患者的细胞免疫及细胞因子水平变化.中国老年学杂志2010，30（15）：2124-2126.
[21]中华医学会.临床诊疗指南（结核病分册）［M］.北京：人民卫生出版社，2005：64-86.
[22] GOLD. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. http://www.goldcopd.com.2010:1–91.
[23] Mueller H, Detjen AK, Schuck SD, et al. Mycobacterium tuberculosis-specific CD4+,IFNgamma+, and TNFalpha+multifunctional memory T cells coexpress GM-CSF.Cytokine,2008,43(2):143-148.
[24] Küpeli E, Karnak D, Beder S, et al. Diagnostic accuracy of cytokine levels(TNF-alpha, IL-2and IFN-gamma) in bronchoalveolar lavage fluid of smear-negativepulmonary tuberculosis patients. Respiration,2008,75(1):73-78.
[25] Cava F, Gonzalez C, Pascual MJ, et al. Biological variation of inter-leukin6(IL-6)and soluble interleukin2receptor (sIL2R) in serum of healthy individuals.Cytokine,2000,12:1423-1425.
[26] Shitrit D, Izbicki G, Bar-Gil Shitrit A, et al. Role of soluble interleukin-2receptorlevels in patients with latent tuberculosis. Lung,2006,184(1):21-24.
[27] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease. Am JRespir Cell Mol Biol,2009,41:631–638.
[28] GadgilA, Zhu X, Sciurba FC, et al. Altered T-cell phenotypes in chronic obstructivepulmonary disease. Proc Am Thorac Soc,2006,3(6):487-488.
[29] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[30] Chensue SW, Warmington KS, Berger AE, et al. Immunohistochemical demonstrationof interleukin-1receptor antagonist protein and interleukin-1in human lymphoidtissue and granulomas. Am J Pathol,1992;140:269-275.
[31] Juffermanns NP, Florquin S, Camoglio L, et al. Interleukin-1signaling is essential forhost defense during murine pulmonary tuberculosis. J Infect Dis,2000;182:902-908.
[32] Law K, Weiden M, Harkin T, et al. Increased release of interleukin-1beta,interleukin-6, and tumor necrosis factor-alpha by bronchoalveolar cells lavaged frominvolved sites in pulmonary tuberculosis. Am J Respir Crit CareMed,1996;153:799-804.
[33] Crisafulli E, Menéndez R, Huerta A,et al. Systemic inflammatory pattern of patientswith community-acquired pneumonia with and without COPD.Chest,2013,143(4):1009-1017.
[34]李红,唐神结.肺结核患者外周血sIL-2R、TNF-ɑ、IFN-γ、IL-6的检测及意义.中国防痨杂志，2011，33（1）:57-60.
[35] Tsao TC, Huang CC, Chiou WK, et al. Levels of interferon-gamma and interleukin-2receptor-alpha for bronchoalveolar lavage fluid and serum were correlated withclinical grade and treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis,2002,6(8):720-727.
[36] Mustafa AS, Al-Saidi F, El-Shamy AS, et al. Cytokines in response to proteinspredicted in genomic regions of difference of Mycobacterium tuberculosis. MicrobiolImmunol,2011,55(4):267-278.
[37] Flynn J. Immunology of tuberculosis and implications in vaccine development.Tuberculosis2004;4:93-101.
[38] Bai X, Wilson SE, Chmura K, et al. Morphometric analysis of Th(1) and Th(2)cytokine expression in human pulmonary tuberculosis. Tuberculosis2004;84:375-385.
[39] Diedrich CR, Mattila JT,Flynn JL. Monocyte-derived IL-5reduces TNF productionby Mycobacterium tuberculosis-specific CD4T cells during SIV/M.tuberculosis coinfection. J Immunol,2013,190(12):6320-6328.
[40] Kumar NP, Sridhar R, Banurekha VV, et al. Type2diabetes mellitus coincident withpulmonary tuberculosis is associated with heightened systemic type1, type17, andother proinflammatory cytokines. Ann Am Thorac Soc,2013,10(5):441-449.
[41] Cozmei C, Constantinescu D, Carasevici E,et al. Th1and Th2cytokine response inpatients with pulmonary tuberculosis and health care workers occupationally exposedto M. tuberculosis. Rev Med Chir Soc Med Nat Iasi,2007,111(3):702-709.
[42] Mat Z, Grensemann B, Yakin Y,et al. Effect of lipoteichoic acid on IL-2and IL-5release from T lymphocytes in asthma and COPD. Int Immunopharmacol,2012,13(3):284-291.
[43] Mattos AM, Almeida Cde S, Franken KL. Increased IgG1, IFN-gamma, TNF-alphaand IL-6responses to Mycobacterium tuberculosis antigens in patients withtuberculosis are lower after chemotherapy. Int Immunol,2010,22(9):775-782.
[44] Donaldson GC, Seemungal TA, Patel IS, et al. Airway and systemic inflammation anddecline in lung function in patients with COPD. Chest,2005,128:1995–2004.
[45] He JQ, Foreman MG, Shumansky K, et al. Associations of IL-6polymorphisms withlung function decline and COPD. Thorax,2009,64:698–704.
[46] Karadag F, Karul AB, Cildag O,et al. Biomarkers of systemic inflammation in stableand exacerbation phases of COPD. Lung,2008,186:403–409.
[47] Yende S, Waterer GW, Tolley EA, et al. Inflammatory markers are associated withventilatory limitation and muscle dysfunction in obstructive lung disease in wellfunctioning elderly subjects. Thorax,2006,61:10-16.
[48] Attaran D, Lari SM, Towhidi M, et al. Interleukin-6and airflow limitation in chemicalwarfare patients with chronic obstructive pulmonary disease. International Journal ofChronic Obstructive Pulmonary Disease,2010,5:335-340.
[49] Djoba Siawaya JF, Beyers N, et al. Differential cytokine secretion and early treatmentresponse in patients with pulmonary tuberculosis. Clin Exp Immunol,2009,156:69-77.
[50] Kaufmann SHE. How can immunology contribute to the control of tuberculosis?Nature Reviews Immunology,2001,1(1):20–30.
[51] Sutherland JS, de Jong BC, Jeffries DJ, et al. Production of TNF-alpha, IL-12(p40)and IL-17can discriminate between active TB disease and latent infection in a WestAfrican cohort. PLoS One,2010,5(8): e12365.
[52] Bekker, L G, Moreira A L, Bergtold A, et al. Immunopathologic effects of tumornecrosis factor alpha in murine mycobacterial infection are dose dependent. InfectImmun,2000,68:6954–6961.
[53] Hodge G, Nairn J, Holmes M, et al. Increased intracellular T helper1proinflammatory cytokineproduction in peripheral blood, bronchoalveolar lavageandintraepithelial T cells of COPD subjects. Clinical and Experimental Immunology,2007,150:22-29.
[54] Lago PM, Boéchat N, Migueis DP, et al. Interleukin-10and interferon-gammapatterns during tuberculosis treatment: possible association with recurrence. Int JTuberc Lung Dis,2012,16(5):656-659.
[55] Ray JC, Wang J, Chan J, et al. The timing of TNF and IFN-gamma signaling affectsmacrophage activation strategies during Mycobacterium tuberculosis infection. JTheor Biol,2008,252(1):24-38.
[56] Kellar KL, Gehrke J, Weis SE, et al. Multiple cytokines are released when blood frompatients with tuberculosis is stimulated with Mycobacterium tuberculosis antigens.PLoS One,2011,6(11): e26545.
[57] Goletti D, Raja A, Ahamed-Kabeer BS, et al. IFN-gamma, but not IP-10, MCP-2orIL-2response to RD1selected peptides associates to active tuberculosis. The Journalof Infection,2010,61(2):133-143.
[58] Jurado JO, Pasquinelli V, Alvarez IB, et al. IL-17and IFN-γ expression inlymphocytes from patients with active tuberculosis correlates with the severity of thedisease. J Leukoc Biol,2012,91(6):991-1002.
[59]张少俊，肖和平.复治肺结核与初治结核病患者外周血T细胞亚群等的变化及其意义.中华结核和呼吸杂志，2011，34(12):884-887.
[60] Aaron SD, Angel JB, Lunau M, et al. Granulocyte inflammatory markers and airwayinfection during acute exacerbation of chronic obstructive pulmonary disease. Am JRespir Crit Care Med,2001,163:349-355.
[61] Bucchioni E, Kharitonov SA, Allegra L, et al. High levels of interleukin-6in theexhaled breath condensate of patients with COPD. Respir Med,2003,97:1299-1302.
[62] Soler N, Ewig S, Torres A, et al. Airway inflammation and bronchial microbialpatterns in patients with stable COPD. Eur Respir J,1999,14(5):1015-1022.
[63] Herfs M, Hubert P, Poirrier AL, et al. Proinflammatory cytokines induce bronchialhyperplasia and squamous metaplasia in smokers: implications for chronic obstructivepulmonary disease therapy. Am J Respir Cell Mol Biol,2012,47(1):67-79.
[64] Lam, KH, Jiang, CQ, Jordan, RE, et al. Prior TB, Smoking, and Airflow Obstruction:A Cross-Sectional Analysis of the Guangzhou Biobank Cohort Study. Chest,2010,137:593-600.
[65] Menezes AMB, Hallal PC., Perez-Padilla R., et al. Tuberculosis and AirflowObstruction: evidence from the PLATINO study in Latin America. EuropeanRespiratory Journal,2007,30:1180-1185.
[66] Chakrabarti B, Calverley PMA, Davies PDO. Tuberculosis and its incidence, specialnature,and relationship with chronic obstructive pulmonary disease. InternationalJournal of COPD,2007,2(3):263-272.
[1] Calverley PM, Walker P.Chronic obstructive pulmonary disease. Lancet,2003,362:1053–1061.
[2] WHO. Global tuberculosis report2013. WHO/HTM/TB/2013.11. Geneva,Switzerland: WHO,2013.
[3] WHO. Global tuberculosis report2012. WHO/HTM/TB/2012.6. Geneva, Switzerland:WHO,2012.
[4]全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调查报告.中华结核和呼吸杂志，2002，25(1):3-7.
[5]全国第五次结核病流行病学抽样调查技术指导组.2010年全国第五次结核病流行病学抽样调查报告.中国防痨杂志，2012，34（8）：485-508.
[6]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[7]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[8]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30：.707-708.
[9] Inghammar M, Ekbom A, Engstr m G, et al. COPD and the Risk of Tuberculosis-APopulation-Based Cohort Study. PLoSONE2010,5(4): e10138.
[10] Liu CH, Yang N, Wang Q, et al.(), Risk factors associated withfluoroquinolone-resistant tuberculosis in a Beijing tuberculosis referral hospital.Respirology,2011,16:918–925.
[11]郑立学，胡忠义.结核病体液免疫检测进展.临床肺科杂志，2000,5(2):86-88.
[12] Abebe F, Bjune G. The protective role of antibody responses during Mycobacteriumtuberculosis infection. The Journal of Translational Immunology,2009,157:235-243.
[13] de Valliere S, Abate G Blazevic A et al. Enhancement of cellmediated immunity byantimycobacterial antibodies. Infect Immun2005;73:6711-20.
[14] Relijic R, Ivanyi J. A case for passive immunoprophylaxis against tuberculosis.Lancet Infect Dis2006;6:813-18.
[15] Pethe K, Alonso S, Biet F et al. The heparin-binding hemagglutinin of M. tuberculosisis required for extrapulmonary dissemination.Nature2001;412:190-4.
[16] Chambers MA, Gavier-Widen D, Hewinson RG. Antibody bound to the surfaceantigen MPB83of Mycobacterium bovis enhances survival against high dose and lowdose challenge. FEMS Immunol Med Microbiol2004;41:93-100.
[17] Shen CY, Hsieh SC, Yu CL, et al. Autoantibody prevalence in active tuberculosis:reactive or pathognomonic? BMJ Open,2013,3(7): pii: e002665.
[18] Boes M. Role of natural and immune IgM antibodies in immune responses. MolImmunol,2000,37:1141-1149.
[19] Le Moigne V, Le Moigne D, Mahana W. Antibody response to Mycobacteriumtuberculosis p27-PPE36antigen in sera of pulmonary tuberculosis patients.Tuberculosis,2013,93(2):189-191.
[20] Glatman-Freedman A. The role of antibody-mediated immunity in defense againstMycobacterium tuberculosis: advances toward a novel vaccine strategy. Tuberculosis(Edinb)2006,86:191-97.
[21] Reljic R. Clark SO, Williams A, et al. Intranasal IFNgamma extends passive IgAantibody protection of mice against Mycobacterium tuberculosis lung infection. ClinExp Immunol,2006,143:467-473.
[22] Mattos AM,Almeida CdeS, Franken KL, et al. Increased IgG1, IFN-gamma,TNF-alpha and IL-6responses to Mycobacterium tuberculosis antigens in patientswith tuberculosis are lower after chemotherapy. International Immunology,2010,22(9):775-782.
[23]佟玉平，李艳丽和张春梅.肺结核病人应用肺活素治疗前后的细胞因子及体液免疫水平检测.黑龙江医学，2008，28（5）：377.
[24] Zu iga J, Torres-García D, Santos-Mendoza T, et al. Cellular and humoralmechanisms involved in the control of tuberculosis. Clinical and developmentalImmunology,2012,2012:193923.
[25]匡铁吉，宋萍，金关甫，等.住院肺结核患者体液免疫水平的变化及其临床意义.军医进修学院学报，1996，17（3）：178-181.
[26] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[27] Musher DM, Groover JE, Rowand JM, et al. Antibody to capsular polysaccharides ofstreptococcus pneumoniae: prevalence, persistence, and response to revaccination.Clin lnfect Dis,1993,17(3):66-73.
[28]黄琛，胡轶，汤汉红.COPD患者肺功能与血清免疫球蛋白及C反应蛋白的关系.医学新知杂志，2008，18（2）：111-112.
[29] Feghali-Bostwick CA, Gadgil AS, Otterbein LE,et al. Autoantibodies in Patients withChronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med,2008:177(2):156-163.
[30] Brandsma CA, Kerstjens HA, van Geffen WH, et al. Differential switching to IgG andIgA in active smoking COPD patients and healthy controls. Eur Respir J,2012,40(2):313-321.
[31] Brandsma C,Hylkema MN,Geerlings M,et al. Increased levels of (class switched)memory B cells in peripheral blood of current smokers. RespiratoryResearch,2009,10:108-118.
[32] Millares L, Marin A, Garcia-Aymerich J, et al. Specific IgA and metalloproteinaseactivity in bronchial secretions from stable chronic obstructive pulmonary diseasepatients colonized by Haemophilus influenza. Respiratory Research,2012,13:113-123.
[33]沈芸，唐神结，孙华等．肺结核合并慢性阻塞性肺疾病患者免疫功能的变化及意义．同济大学学报（医学版）．2012，33（1）：53-58．
[34]朱友生，唐神结.巨噬细胞在抗结核免疫中的作用及其研究进展.中国防痨杂志，2004，26（3）：173-175.
[35]唐神结，肖和平.细胞因子网络与结核病.中华结核和呼吸杂志2001，24（9）：571-574.
[36] Kim W D, Kim W S, Koh Y. Abnormal peripheral bloodT-lymphocyte subsets in a subgroup of patients with COPD. Chest.,2002,122(2):437-444.
[37] Shirai T, Suda T, Inui N. Correlation between peripheral bloodT-cell profiles and clinical and inflammatory parameters in stableCOPD. Allergol Int,2010,59(1):75-82.
[38]汤其岭．COPD患者治疗前后血清SOD和T淋巴细胞亚群检测的临床意义．淮海医药，2008，26（6）：486-487．
[39]夏晓东，刘道候，徐永安，等.慢性阻塞性肺疾病患者T细胞亚群动态变化.浙江实用医学，2008,13（2）:85-86.
[40] Malin Inghammar, M., Anders Ekbom, A., Engstr m, G., et al. COPD and the Risk ofTuberculosis-A Population-Based Cohort Study. PLoS One,2010,5(4): e10138.
[41] Shenjie Tang, Haiyan Cui, Lan Yao,et al.Increased Cytokines Response in Patientswith Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease. PLOSONE,2013,8(4):e62385.
[42] Zahran WA，Ghonaim MM, Koura BA, EI-Banna H, Ali SM, EI-Sheikh N.Humannatural killer T cells(NKT),NK and T cells in pulmonary tuberculosis:potentialindicators for disease activity and prognosis. Egypt J Immunol.2006,13(1):67-78.
[43] Kulpraneet M, Sukwit S, Sumransurp K, et al. Cytokine production in NK and NKTcells from Mycobacterium tuberculosis infected patients. Southeast Asian J Trop MedPublic Health,2007,38(2):370-375.
[44] Leung W L,Law K L, Leung V S et al. Comparison of intracellular cytokine flowcytometry and an enzyme immunoassay for evaluat ion of cellularimmune response toactive tuberculosis. Clin Vaccine Immunol,2009;16(3):344-351.
[45]翟慧,刘一典,唐神结,等.肺结核患者外周血NKT细胞、NK细胞、T淋巴细胞亚群的变化及意义.同济大学学报(医学版),2010;31(5):42-46.
[46]孙巍，杨永辉，李登瑞，等.NKT细胞、NK细胞和T细胞亚群在活动性肺结核患者外周血的表达及意义.中国免疫杂志，2011，27（11）：1030-1034.
[47]张青，肖和平． T细胞、NKT细胞和NK细胞在结核病诊断中的意义探讨．中国防痨杂志，2010，32(5):267-271．
[48]邱晓静，王兆华，王健，等.肺结核患者外周血NK细胞数量和胞内杀伤分子的变化.蚌埠医学院学报，2012，37（10）：1141-1144.
[49]周晓映，于红艳，王惠青，等.2型糖尿病合并肺结核患者T淋巴细胞亚群和NK细胞的变化及其临床意义.疑难病杂志，2008，7（11）：666-668.
[50]王心静，杨秉芬，原艳明，等.初治菌阳肺结核患者外周血NK细胞比例显著下降.免疫学杂志，2013，29（8）：677-680.
[51] Portevin D, Via LE, Eum S, et al. Natural killer cells are recruited during pulmonarytuberculosis and their ex vivo responses to mycobacteria vary between healthy humandonors in association with KIR haplotype. Cell Microbiol,2012,14(11):1734-1744.
[52] Vankayalapati R, Wizel B, Weis SE, et al. The NKp46receptor contributes to NK celllysis of mononuclear phagocytes infected with an intracellular bacterium. JImmunol,2002,168(7):3451-3457.
[53]付笑迎,李丽,李琴,等.结核性胸液中NK细胞的亚群及表型功能特征分析.免疫学杂志,2012,28(8):691-694.
[54]黄美健，冷报浪，梁斌，等.慢性阻塞性肺疾病不同病期细胞免疫功能的临床研究.浙江实用医学,2004,6（8）:664-665.
[55]傅佩芳，殷少军，颜正茂，等。慢性阻塞性肺疾病患者与免疫功能关系的临床研究。中国现代医学杂志，2008，18（3）：338-340.
[56]王娜，夏婧.慢性阻塞性肺疾病患者免疫功能的变化.贵州医药，2011，35（7）:593-595.
[57]张蔚，江山平，吕志强，等.慢性阻塞性肺疾病患者外周血T淋巴细胞亚群和NK细胞的动态变化.中山大学学报（医学科学版），2005，3S：115-116.
[58] Mueller H, Detjen AK, Schuck SD, et al. Mycobacterium tuberculosis-specific CD4+,IFNgamma+, and TNFalpha+multifunctional memory T cells coexpress GM-CSF.Cytokine,2008,43(2):143-148.
[59] Küpeli E, Karnak D, Beder S, et al. Diagnostic accuracy of cytokine levels(TNF-alpha, IL-2and IFN-gamma) in bronchoalveolar lavage fluid of smear-negativepulmonary tuberculosis patients. Respiration,2008,75(1):73-78.
[60] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scand JImmunol,2012,75(6):623-632.
[61] Shitrit D, Izbicki G, Bar-Gil Shitrit A, et al. Role of soluble interleukin-2receptorlevels in patients with latent tuberculosis. Lung,2006,184(1):21-24.
[62] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease. Am JRespir Cell Mol Biol,2009,41:631–638.
[63] GadgilA, Zhu X, Sciurba FC, et al. Altered T-cell phenotypes in chronic obstructivepulmonary disease. Proc Am Thorac Soc,2006,3(6):487-488.
[64] Katti MK. Assessment of serum IL-1, IL-2and IFN-γ levels in untreated pulmonarytuberculosis patients: role in pathogenesis. Archives of Medical Research,2011,42(3):199-201.
[65] Crisafulli E, Menéndez R, Huerta A,et al. Systemic inflammatory pattern of patientswith community-acquired pneumonia with and without COPD. Chest,2013,143(4):1009-1017.
[66]李红,唐神结.肺结核患者外周血sIL-2R、TNF-ɑ、IFN-γ、IL-6的检测及意义.中国防痨杂志，2011，33（1）:57-60.
[67] Tsao TC, Huang CC, Chiou WK, et al. Levels of interferon-gamma and interleukin-2receptor-alpha for bronchoalveolar lavage fluid and serum were correlated withclinical grade and treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis,2002,6(8):720-727.
[68] Mustafa AS, Al-Saidi F, El-Shamy AS, et al. Cytokines in response to proteinspredicted in genomic regions of difference of Mycobacterium tuberculosis. MicrobiolImmunol,2011,55(4):267-278.
[69] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scandinavian Journalof Immunology,2012,75(6):623-632.
[70] Diedrich CR, Mattila JT,Flynn JL. Monocyte-derived IL-5reduces TNF productionby Mycobacterium tuberculosis-specific CD4T cells during SIV/M.tuberculosis coinfection. J Immunol,2013,190(12):6320-6328.
[71] Kumar NP, Sridhar R, Banurekha VV, et al. Type2diabetes mellitus coincident withpulmonary tuberculosis is associated with heightened systemic type1, type17, andother proinflammatory cytokines. Ann Am Thorac Soc,2013,10(5):441-449.
[72] Cozmei C, Constantinescu D, Carasevici E,et al. Th1and Th2cytokine response inpatients with pulmonary tuberculosis and health care workers occupationally exposedto M. tuberculosis. Rev Med Chir Soc Med Nat Iasi,2007,111(3):702-709.
[73] Mat Z, Grensemann B, Yakin Y,et al. Effect of lipoteichoic acid on IL-2and IL-5release from T lymphocytes in asthma and COPD. Int Immunopharmacol,2012,13(3):284-291.
[74] Mattos AM, Almeida CS, Franken KL. Increased IgG1, IFN-gamma, TNF-alpha andIL-6responses to Mycobacterium tuberculosis antigens in patients with tuberculosisare lower after chemotherapy. Int Immunol,2010,22(9):775-782.
[75] He JQ, Foreman MG, Shumansky K, et al. Associations of IL-6polymorphisms withlung function decline and COPD. Thorax,2009,64:698–704.
[76] Karadag F, Karul AB, Cildag O,et al. Biomarkers of systemic inflammation in stableand exacerbation phases of COPD. Lung,2008,186:403–409.
[77] Yende S, Waterer GW, Tolley EA, et al. Inflammatory markers are associated withventilatory limitation and muscle dysfunction in obstructive lung disease in wellfunctioning elderly subjects. Thorax,2006,61:10-16.
[78] Attaran D, Lari SM, Towhidi M, et al. Interleukin-6and airflow limitation in chemicalwarfare patients with chronic obstructive pulmonary disease. International Journal ofChronic Obstructive Pulmonary Disease,2010,5:335-340.
[79] Djoba Siawaya JF, Beyers N, et al. Differential cytokine secretion and early treatmentresponse in patients with pulmonary tuberculosis. Clin Exp Immunol,2009,156:69-77.
[80] Nemeth J, Winkler HM, Boeck L, et al. Specific cytokine patterns of pulmonarytuberculosis in Central Africa. Clin Immunol,2011,138(1):50-59.
[81] Sutherland JS, de Jong BC, Jeffries DJ, et al. Production of TNF-alpha, IL-12(p40)and IL-17can discriminate between active TB disease and latent infection in a WestAfrican cohort. PLoS One,2010,5(8): e12365.
[82] Moermans C, Heinen V, Nguyen M, et al. Local and systemic cellular inflammationand cytokine release in chronic obstructive pulmonary disease. Cytokine,2011,56(2):298-304.
[83] Hodge G, Nairn J, Holmes M, et al. Increased intracellular T helper1proinflammatory cytokineproduction in peripheral blood, bronchoalveolar lavageandintraepithelial T cells of COPD subjects. Clinical and Experimental Immunology,2007,150:22-29.
[84] Lago PM, Boéchat N, Migueis DP, et al. Interleukin-10and interferon-gammapatterns during tuberculosis treatment: possible association with recurrence. Int JTuberc Lung Dis,2012,16(5):656-659.
[85] Ray JC, Wang J, Chan J, et al. The timing of TNF and IFN-gamma signaling affectsmacrophage activation strategies during Mycobacterium tuberculosis infection. JTheor Biol,2008,252(1):24-38.
[86] Kellar KL, Gehrke J, Weis SE, et al. Multiple cytokines are released when blood frompatients with tuberculosis is stimulated with Mycobacterium tuberculosis antigens.PLoS One,2011,6(11): e26545.
[87] Goletti D, Raja A, Ahamed-Kabeer BS, et al. IFN-gamma, but not IP-10, MCP-2orIL-2response to RD1selected peptides associates to active tuberculosis. The Journalof Infection,2010,61(2):133-143.
[2] GOLD Executive Committee. Global strategy for the diagnosis,management,andprevention of chronic obstructive pulmonary disease(Revised2011)[EB/OL].[2012-01-16].http://www.goldcopd.com
[3] Calverley PM, Walker P.Chronic obstructive pulmonary disease. Lancet,2003,362:1053–1061.
[4] WHO. Global tuberculosis report2013. WHO/HTM/TB/2013.11. Geneva,Switzerland: WHO,2013.
[5] WHO. Global tuberculosis report2012. WHO/HTM/TB/2012.6. Geneva, Switzerland:WHO,2012.
[6]全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调查报告.中华结核和呼吸杂志，2002，25(1):3-7.
[7]全国第五次结核病流行病学抽样调查技术指导组.2010年全国第五次结核病流行病学抽样调查报告.中国防痨杂志，2012，34（8）：485-508.
[8]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[9]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[10]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30:707-708.
[11] Inghammar M, Ekbom A, Engstr m G, et al. COPD and the Risk of Tuberculosis-APopulation-Based Cohort Study. PLoSONE2010,5(4): e10138.
[12] Liu CH, Yang N, Wang Q, et al.(), Risk factors associated withfluoroquinolone-resistant tuberculosis in a Beijing tuberculosis referral hospital.Respirology,2011,16:918–925.
[13]郑立学，胡忠义.结核病体液免疫检测进展.临床肺科杂志，2000,5(2):86-88.
[14] Abebe F, Bjune G. The protective role of antibody responses during Mycobacteriumtuberculosis infection. The Journal of Translational Immunology,2009,157:235-243.
[15] de Valliere S, Abate G Blazevic A et al. Enhancement of cellmediated immunity byantimycobacterial antibodies. Infect Immun2005;73:6711-20.
[16] Relijic R, Ivanyi J. A case for passive immunoprophylaxis against tuberculosis.Lancet Infect Dis2006;6:813-18.
[17] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[18] Brandsma CA, Kerstjens HA, van Geffen WH, et al. Differential switching to IgG andIgA in active smoking COPD patients and healthy controls. Eur Respir J,2012,40(2):313-321.
[19] Feghali-Bostwick CA, Gadgil AS, Otterbein LE, et al. Autoantibodies in Patientswith Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med,2008:177(2):156-163.
[20]朱友生，唐神结.巨噬细胞在抗结核免疫中的作用及其研究进展.中国防痨杂志，2004，26（3）：173-175.
[21]唐神结，肖和平.细胞因子网络与结核病.中华结核和呼吸杂志2001，24（9）：571-574.
[22] Shirai T, Suda T, Inui N. Correlation between peripheral blood T-cell profilesand clinical and inflammatory parameters in stable COPD. Allergol Int,2010,59(1):75-82.
[23] Shenjie Tang, Haiyan Cui, Lan Yao,et al. Increased Cytokines Response in Patientswith Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease. PLOSONE,2013,8(4):e62385.
[24] Zahran WA，Ghonaim MM, Koura BA, et al. Human natural killer T cells(NKT),NKand T cells in pulmonary tuberculosis:potential indicators for disease activity andprognosis. Egypt J Immunol.2006,13(1):67-78.
[25] Kulpraneet M, Sukwit S, Sumransurp K, et al. Cytokine production in NK and NKTcells from Mycobacterium tuberculosis infected patients. Southeast Asian J Trop MedPublic Health,2007,38(2):370-375.
[26]翟慧,刘一典,唐神结,等.肺结核患者外周血NKT细胞、NK细胞、T淋巴细胞亚群的变化及意义.同济大学学报(医学版),2010;31(5):42-46.
[27]张蔚，江山平，吕志强，等.慢性阻塞性肺疾病患者外周血T淋巴细胞亚群和NK细胞的动态变化.中山大学学报（医学科学版），2005，3S：115-116.
[28] Mueller H, Detjen AK, Schuck SD, et al. Mycobacterium tuberculosis-specific CD4+,IFNgamma+, and TNFalpha+multifunctional memory T cells coexpress GM-CSF.Cytokine,2008,43(2):143-148.
[29] Küpeli E, Karnak D, Beder S, et al. Diagnostic accuracy of cytokine levels(TNF-alpha, IL-2and IFN-gamma) in bronchoalveolar lavage fluid of smear-negativepulmonary tuberculosis patients. Respiration,2008,75(1):73-78.
[30] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scand JImmunol,2012,75(6):623-632.
[31] Shitrit D, Izbicki G, Bar-Gil Shitrit A, et al. Role of soluble interleukin-2receptorlevels in patients with latent tuberculosis. Lung,2006,184(1):21-24.
[32] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease. Am JRespir Cell Mol Biol,2009,41:631–638.
[33] GadgilA, Zhu X, Sciurba FC, et al. Altered T-cell phenotypes in chronic obstructivepulmonary disease. Proc Am Thorac Soc,2006,3(6):487-488.
[1] Calverley PM, Walker P.Chronic obstructive pulmonary disease. Lancet,2003,362:1053–1061.
[2] WHO. Global tuberculosis report2013. WHO/HTM/TB/2013.11. Geneva,Switzerland: WHO,2013.
[3] WHO. Global tuberculosis report2012. WHO/HTM/TB/2012.6. Geneva, Switzerland:WHO,2012.
[4]全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调查报告.中华结核和呼吸杂志，2002，25(1):3-7.
[5]全国第五次结核病流行病学抽样调查技术指导组.2010年全国第五次结核病流行病学抽样调查报告.中国防痨杂志，2012，34（8）：485-508.
[6]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[7]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[8]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30：.707-708.
[9] Inghammar M, Ekbom A, Engstr m G, et al. COPD and the Risk of Tuberculosis-APopulation-Based Cohort Study. PLoSONE2010,5(4): e10138.
[10] Liu CH, Yang N, Wang Q, et al. Risk factors associated with fluoroquinolone-resistanttuberculosis in a Beijing tuberculosis referral hospital. Respirology,2011,16:918–925.
[11]郑立学，胡忠义.结核病体液免疫检测进展.临床肺科杂志，2000,5(2):86-88.
[12]黄奕江,冯夏,郑万川.慢性阻塞性肺疾病患者免疫功能研究.临床内科杂志,1997,14(1):30.
[13]吴纪珍，张罗献，马利军，等。老年慢性阻塞性肺疾病患者免疫功能测定及其意义。医药论坛杂志，25（23）：10-12。
[14] Musher DM, Groover JE, Rowand JM, et al. Antibody to capsular polysaccharides ofstreptococcus pneumoniae: prevalence, persistence, and response to revaccination.Clin lnfect Dis,1993,17(3):66-73.
[15] Ghimire Hridaya, Li Jian. Role of Latent Tuberculosis Infection in the Pathogenesisand Severity of COPD. Chest.2011,140（4_Meeting Abstracts）:564A.
[16] Ernst P, Suissa S. Systemic effects of inhaled corticosteroids. Curr Opin Pulm Med.2012,18(1):85-89.
[17] Shu CC, Wu HD, Yu MC. Use of High-Dose Inhaled Corticosteroids is AssociatedWith Pulmonary Tuberculosis in Patients With Chronic Obstructive PulmonaryDisease. Medicine.2010,89(1):53-61.
[18]中华医学会.临床诊疗指南（结核病分册）［M］.北京：人民卫生出版社，2005：64-86.
[19] GOLD. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. http://www.goldcopd.com.2010:1–91.
[20]王巍，王安生。结核病细胞免疫和体液免疫研究的若干研究。中国防痨杂志，1997，19（4）：197-200。
[21] Maglione PJ, Chan J. How B cells shape the immune response againstMycobacterium tuberculosis. European Journal of Immunology,2009,39:676-686.
[22] Abebe F, Bjune G. The protective role of antibody responses during Mycobacteriumtuberculosis infection. The Journal of Translational Immunology,2009,157:235-243.
[23] de Valliere S, Abate G, Blazevic A, et al. Enhancement of cellmediated immunity byantimycobacterial antibodies. Infect Immun2005;73:6711-20.
[24] Relijic R, Ivanyi J. A case for passive immunoprophylaxis against tuberculosis.Lancet Infect Dis2006;6:813-18.
[25] Pethe K, Alonso S, Biet F et al. The heparin-binding hemagglutinin of M. tuberculosisis required for extrapulmonary dissemination.Nature2001;412:190-4.
[26] Chambers MA, Gavier-Widen D, Hewinson RG. Antibody bound to the surfaceantigen MPB83of Mycobacterium bovis enhances survival against high dose and lowdose challenge. FEMS Immunol Med Microbiol2004;41:93-100.
[27] Shen CY, Hsieh SC, Yu CL, et al. Autoantibody prevalence in active tuberculosis:reactive or pathognomonic? BMJ Open,2013,3(7): pii: e002665.
[28] Boes M. Role of natural and immune IgM antibodies in immune responses. MolImmunol,2000,37:1141-1149.
[29]周世明,贾杰,杨建国.乌体林斯治疗肺结核前后免疫功能的改变济临床意义.中国热带医学杂志,2003,3(5):623.
[30]韩庆,王怀诚.观察人体胎盘脂多糖辅助治疗初治菌阳肺结核疗效及安全性.江苏医药,2006,32(12):1191.
[31]何菊芳，佟爱华，董梅，等.肺结核患者血清蛋白电泳图谱与体液免疫水平相关性的探讨.中国实验诊断学，2011，15（10）：1742-1743.
[32] Le Moigne V, Le Moigne D, Mahana W. Antibody response to Mycobacteriumtuberculosis p27-PPE36antigen in sera of pulmonary tuberculosis patients.Tuberculosis,2013,93(2):189-191.
[33] Glatman-Freedman A. The role of antibody-mediated immunity in defense againstMycobacterium tuberculosis: advances toward a novel vaccine strategy. Tuberculosis(Edinb)2006,86:191-97.
[34] Reljic R. Clark SO, Williams A, et al. Intranasal IFNgamma extends passive IgAantibody protection of mice against Mycobacterium tuberculosis lung infection. ClinExp Immunol,2006,143:467-473.
[35] Hamasur B, Haile M, Pawlowski A, et al. A mycobacterial lipoarabinomannanspecific monoclonal antibody and its F(ab0) fragment prolong survival of miceinfected with Mycobacterium tuberculosis. Clin Exp Immunol,2004,138:30-38.
[36] Williams A, Reljic R, Naylor I, et al. Passive protection with immunoglobulin Aantibodies against tuberculous early infection of the lungs. Immunology,2004,111:328-333.
[37] Mattos AM,Almeida CdeS, Franken KL, et al. Increased IgG1, IFN-gamma,TNF-alpha and IL-6responses to Mycobacterium tuberculosis antigens in patientswith tuberculosis are lower after chemotherapy. International Immunology,2010,22(9):775-782.
[38]佟玉平，李艳丽和张春梅.肺结核病人应用肺活素治疗前后的细胞因子及体液免疫水平检测.黑龙江医学，2008，28（5）：377.
[39] Zu iga J, Torres-García D, Santos-Mendoza T, et al. Cellular and humoralmechanisms involved in the control of tuberculosis. Clinical and developmentalImmunology,2012,2012:193923.
[40] Costello DAM, Kumar A, Narayan V et al.“Does antibody to mycobacterial antigens,including lipoarabinomannan, limit dissemination in childhood tuberculosis?”Transactions of the Royal Society of Tropical Medicine and Hygiene,1992,86(6):686-692.
[41] da Costa CTKA, Khanolkar-Young S, Elliott AM, et al.“Immunoglobulin G subclassresponses tomycobacterial lipoarabinomannan in HIV-infected and non-infectedpatients with tuberculosis,” Clinical and Experimental Immunology,1993,91(1):25-29.
[42]匡铁吉，宋萍，金关甫，等.住院肺结核患者体液免疫水平的变化及其临床意义.军医进修学院学报，1996，17（3）：178-181.
[43]尹洪云,徐家琏.慢性阻塞性肺疾病与肺结核的关系.中国临床医生，2004，32(8)：12-14.
[44] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[45]朱渊红,王新华,王真,等.60例慢性阻塞性肺疾病细胞免疫功能的临床观察.浙江实用医学,2005,10（5）:321-322.
[46]黄琛，胡轶，汤汉红.COPD患者肺功能与血清免疫球蛋白及C反应蛋白的关系.医学新知杂志，2008，18（2）：111-112.
[47] Feghali-Bostwick CA, Gadgil AS, Otterbein LE,et al. Autoantibodies in Patients withChronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med,2008:177(2):156-163.
[48] Brandsma CA, Kerstjens HA, van Geffen WH, et al. Differential switching to IgG andIgA in active smoking COPD patients and healthy controls. Eur Respir J,2012,40(2):313-321.
[49] Brandsma C, Hylkema MN, Geerlings M, et al. Increased levels of (class switched)memory B cells in peripheral blood of current smokers. RespiratoryResearch,2009,10:108-118.
[50] Millares L, Marin A, Garcia-Aymerich J, et al. Specific IgA and metalloproteinaseactivity in bronchial secretions from stable chronic obstructive pulmonary diseasepatients colonized by Haemophilus influenza. Respiratory Research,2012,13:113-123.
[51]沈芸，唐神结，孙华，郝晓晖．肺结核合并慢性阻塞性肺疾病患者免疫功能的变化及意义．同济大学学报（医学版）．2012，33（1）：53-58．
[1]朱友生，唐神结.巨噬细胞在抗结核免疫中的作用及其研究进展.中国防痨杂志，2004，26（3）：173-175.
[2]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[3]唐神结，肖和平.细胞因子网络与结核病.中华结核和呼吸杂志2001，24（9）：571-574.
[4] Zahran WA，Ghonaim MM, Koura BA, et al. Human natural killer T cells(NKT),NKand T cells in pulmonary tuberculosis:potential indicators for disease activity andprognosis. Egypt J Immunol.2006,13(1):67-78.
[5] Kulpraneet M, Sukwit S, Sumransurp K, et al. Cytokine production in NK and NKTcells from Mycobacterium tuberculosis infected patients. Southeast Asian J Trop MedPublic Health,2007,38(2):370-375.
[6] Vankayalapati R, Klucar P, Wizel B, et al. NK cells regulate CD8+Tcell effectorfunction in response to an intracellular pathogen. J Immunol,2004,172:130-137.
[7] Schierloh P, Yokobori N, Aleman M, et al. Mycobacterium tuberculosis-InducedGamma Interferon Production by Natural Killer Cells Requires Cross Talk withAntigen-Presenting Cells Involving Toll-Like Receptors2and4and the MannoseReceptor in Tuberculous Pleurisy.Infect and Immun,2007,75(11):5325-5337.
[8] Nirmala R, Narayanan PR, Mathew R, et al. Reduced NK activity in pulmonarytuberculosis patients with/without HIV infection: identifying the defective stage andstudying the effect of interleukins on NK activity.Tuberculosis,2001,81（5-6）:343-352.
[9] Deveci F， Akbulut HH， Celik I. Lymphocyte subpopulations in pulmonarytuberculosis patients.Mediators Inflamm,2006，2006(2):89070.
[10] Yildiz P, Kadakal F, Tutuncu Y, et al. Natural killer cell activity in multidrug-resistantpulmonary tuberculosis. Respiration,2001,68（6）:590-594.
[11] Kim W D, Kim W S, Koh Y. Abnormal peripheral blood T-lymphocytesubsets in a subgroup of patients with COPD. Chest.,2002,122(2):437-444.
[12] Shirai T, Suda T, Inui N. Correlation between peripheral blood T-cell profilesand clinical and inflammatory parameters in stable COPD. Allergol Int,2010,59(1):75-82.
[13] Glader P, von Wachenfeldt K, et al. Systemic CD4+T-cell activation is correlated with FEV1insmoker. Respir Med2006,100(6):1088-1093.
[14] Majo J， Ghezzo H， Cosio MG． Lymphocyte population and apoptosis in the lungs of smokersand their relation to emphysema． Eur Respir J,2001,17：946-953．
[15]崔微艳，陆洁，邹静蓉，等．慢性阻塞性肺疾病患者外周血T细胞亚群分析.岭南急诊医学杂志，2008，13（6）:414-415.
[16]汤其岭．COPD患者治疗前后血清SOD和T淋巴细胞亚群检测的临床意义．淮海医药，2008，26（6）：486-487．
[17]夏晓东，刘道候，徐永安，等.慢性阻塞性肺疾病患者T细胞亚群动态变化.浙江实用医学，2008,13（2）:85-86.
[18]黄美健，冷报浪，梁斌，等.慢性阻塞性肺疾病不同病期细胞免疫功能的临床研究.浙江实用医学,2004,6（8）:664-665.
[19]傅佩芳，殷少军，颜正茂，等。慢性阻塞性肺疾病患者与免疫功能关系的临床研究。中国现代医学杂志，2008，18（3）：338-340.
[20]王娜，夏婧.慢性阻塞性肺疾病患者免疫功能的变化.贵州医药，2011，35（7）:593-595.
[21]中华医学会.临床诊疗指南（结核病分册）［M］.北京：人民卫生出版社，2005：64-86.
[22] GOLD. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. http://www.goldcopd.com.2010:1–91.
[23] Chen CY, Huang D, Wang RC, et al. A critical role for CD8T cells in a nonhumanprimate model of tuberculosis. PLoS Pathogens,2009,5:e1000392.
[24] Elvang T, Christensen JP, Billeskov R, et al. CD4and CD8T cell responses to the M.tuberculosis Ag85B-TB10.4promoted by adjuvanted subunit, adenovector orheterologous prime boost vaccination.PLoS One,2009;4(4):e5139.
[25] Kiran B, Cagatay T, Clark P, et al. Can immune parameters be used as predictors todistinguish between pulmonary multidrug-resistant and drug-sensitive tuberculosis?Arch Med Sci,2010,6(1):77-82.
[26]杨妍，唐神结，张青，等.耐多药和广泛耐药肺结核患者外周血中免疫细胞的表达及其意义.中华结核和呼吸杂志,2011,34（2）:109-113.
[27]翟慧,刘一典,唐神结,等.肺结核患者外周血NKT细胞、NK细胞、T淋巴细胞亚群的变化及意义.同济大学学报(医学版),2010;31(5):42-46.
[28] Caccamo N, Guggino G, Joosten SA, et al. Multifunctional CD4(+) T cells correlate with activeMycobacterium tuberculosis infection. European Journal of Immunology,2010,40(8):2211-2220.
[29] Koch A, Gaczkowski M, Sturton G et al. Modification of surface antigens in bloodCD8+T-lymphocytes in COPD: effects of smoking. Eur Respir J,2007,29(1):42-50.
[30]张蔚，江山平，吕志强，等。慢性阻塞性肺疾病患者外周血T淋巴细胞亚群和NK细胞的动态变化。中山大学学报（医学科学版），2005，3S：115-116
[31] Kim WD, Kim WS, Koh Y, et al. Abnormal peripheral blood T-lymphocyte subsets ina subgroup of patients with COPD. Chest,2002,122(2):437-444.
[32] Chen C, Shen Y, Ni CJ, et al. Imbalance of Circulating T-Lymphocyte Subpopulationin COPD and its Relationship with CAT Performance. Journal of Clinical LaboratoryAnalysis,2012,26(2):109-114.
[33] Paats MS, Bergen IM, Hoogsteden HC, et al. Systemic CD4+and CD8+T-cellcytokine profiles correlate with GOLD stage in stable COPD. Eur RespirJ,2012,40(2):330-7.
[34] Domaga a-Kulawik J, Hoser G, Dabrowska M, et al. Increased proportion of Faspositive CD8+cells in peripheral blood of patients with COPD. Respiratory Medicine,2007,101(6):1338-1343.
[35] L fdahl MJ, Roos-Engstrand E, Pourazar J, et al. Increased intraepithelial T-cells instable COPD. Respiratory Medicine,2008,102(12):1812-1818.
[36] Malin Inghammar M, Anders Ekbom A, Engstr m G, et al. COPD and the Risk ofTuberculosis-A Population-Based Cohort Study. PLoS One,2010,5(4): e10138.
[37] Leung WL, Law KL, Leung VS et al. Comparison of intracellular cytokine flowcytometry and an enzyme immunoassay for evaluat ion of cellularimmune response toactive tuberculosis. Clin Vaccine Immunol,2009;16(3):344-351.
[38]孙巍，杨永辉，李登瑞，等.NKT细胞、NK细胞和T细胞亚群在活动性肺结核患者外周血的表达及意义.中国免疫杂志，2011，27（11）：1030-1034.
[39]张青，肖和平． T细胞、NKT细胞和NK细胞在结核病诊断中的意义探讨．中国防痨杂志，2010，32(5):267-271．
[40]邱晓静，王兆华，王健，等.肺结核患者外周血NK细胞数量和胞内杀伤分子的变化.蚌埠医学院学报，2012，37（10）：1141-1144.
[41]周晓映，于红艳，王惠青，等.2型糖尿病合并肺结核患者T淋巴细胞亚群和NK细胞的变化及其临床意义.疑难病杂志，2008，7（11）：666-668.
[42]王心静，杨秉芬，原艳明，等.初治菌阳肺结核患者外周血NK细胞比例显著下降.免疫学杂志，2013，29（8）：677-680.
[43] Portevin D, Via LE, Eum S, et al. Natural killer cells are recruited during pulmonarytuberculosis and their ex vivo responses to mycobacteria vary between healthy humandonors in association with KIR haplotype. Cell Microbiol,2012,14(11):1734-1744.
[44] Vankayalapati R, Wizel B, Weis SE, et al. The NKp46receptor contributes to NKcell lysis of mononuclear phagocytes infected with an intracellular bacterium. JImmunol,2002,168(7):3451-3457.
[45]付笑迎,李丽,李琴,等.结核性胸液中NK细胞的亚群及表型功能特征分析.免疫学杂志,2012,28(8):691-694.
[1]唐神结，肖和平.细胞因子网络与结核病.中华结核与呼吸杂志，2001,24（9）571-574.
[2] Sutherland JS, Garba D, Fombah AE et al. Highly accurate diagnosis of pleuraltuberculosis by immunological analysis of the pleural effusion. Plos One.2012;7(1):e30324.
[3] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scandinavian Journalof Immunology,2012,75(6):623-632.
[4]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[5]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30：.707-708.
[6]李红，唐神结.肺结核患者外周血sIL-2R、TNF-、IFN-γ、IL-6的检测及意义.中国防痨杂志，2011，33（1）：57-60.
[7]杨妍，唐神结，张青，等.耐多药和广泛耐药肺结核患者外周血中免疫细胞的表达及其意义.中华结核和呼吸杂志,2011,34（2）:109-113.
[8]唐神结，肖和平，范以虎，等.肺结核患者支气管肺泡灌洗液中某些细胞因子和受体的检测及其临床意义.中华传染病杂志，2009，27（3）：167-171.
[9] Katti MK. Assessment of serum IL-1, IL-2and IFN-γ levels in untreated pulmonarytuberculosis patients: role in pathogenesis. Archives of Medical Research,2011,42(3):199-201.
[10] Nemeth J, Winkler HM, Boeck L, et al. Specific cytokine patterns of pulmonarytuberculosis in Central Africa. Clinical Immunology.2011,138(1):50-59.
[11] Cui HY, Zhang Q, Su B, et al. Differential levels of cytokines and soluble Fas ligandbetween tuberculous and malignant effusions. The Journal of International Research,2010,38(6):2063-2069.
[12] Agusti A,Soriano JB.COPD as a systemic disease.COPD,2008,5(2):133-138.
[13] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease.American Journal of Respiratory Cell and Molecular Biology,2009,41:631-638.
[14] Kent L, Smyth L, Clayton C, et al. Cigarette smoke extract induced cytokine andchemokine gene expression changes in COPD macrophages.Cytokine,2008,42(2):205-216.
[15] Pinto-Plata VM, Livnat G, Girish M, et al. Systemic cytokines， clinical andphysiological changes in patients hospitalized for exacerbation ofCOPD.Chest,2007,131(1):37-43.
[16] Bathoorn E, Liesker JJ, Postma DS, et al.COPD patients from stable phase to a subsequent exacerbation. Int J Chron ObstructPulmon Dis,2009,4(1):101-109.
[17] Hacievliyagil SS, Gunen H, Mutlu LC, et al. Association between cytokines ininduced sputum and severity of chronic obstructive pulmonary disease. RespirMed,2006,100(5):846-854.
[18]吴纪珍，张罗献，马利军，等.老年慢性阻塞性肺疾病患者免疫功能测定及其意义。医药论坛杂志，2004，25（23）：10-12.
[19] Moermans C, Heinen V, Nguyen M, et al. Local and systemic cellular inflammationand cytokine release in chronic obstructive pulmonary disease. Cytokine,2011,56(2):298-304.
[20]孙雯雯，李燕芹，刘斌，等.慢性阻塞性肺疾病患者的细胞免疫及细胞因子水平变化.中国老年学杂志2010，30（15）：2124-2126.
[21]中华医学会.临床诊疗指南（结核病分册）［M］.北京：人民卫生出版社，2005：64-86.
[22] GOLD. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease. http://www.goldcopd.com.2010:1–91.
[23] Mueller H, Detjen AK, Schuck SD, et al. Mycobacterium tuberculosis-specific CD4+,IFNgamma+, and TNFalpha+multifunctional memory T cells coexpress GM-CSF.Cytokine,2008,43(2):143-148.
[24] Küpeli E, Karnak D, Beder S, et al. Diagnostic accuracy of cytokine levels(TNF-alpha, IL-2and IFN-gamma) in bronchoalveolar lavage fluid of smear-negativepulmonary tuberculosis patients. Respiration,2008,75(1):73-78.
[25] Cava F, Gonzalez C, Pascual MJ, et al. Biological variation of inter-leukin6(IL-6)and soluble interleukin2receptor (sIL2R) in serum of healthy individuals.Cytokine,2000,12:1423-1425.
[26] Shitrit D, Izbicki G, Bar-Gil Shitrit A, et al. Role of soluble interleukin-2receptorlevels in patients with latent tuberculosis. Lung,2006,184(1):21-24.
[27] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease. Am JRespir Cell Mol Biol,2009,41:631–638.
[28] GadgilA, Zhu X, Sciurba FC, et al. Altered T-cell phenotypes in chronic obstructivepulmonary disease. Proc Am Thorac Soc,2006,3(6):487-488.
[29] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[30] Chensue SW, Warmington KS, Berger AE, et al. Immunohistochemical demonstrationof interleukin-1receptor antagonist protein and interleukin-1in human lymphoidtissue and granulomas. Am J Pathol,1992;140:269-275.
[31] Juffermanns NP, Florquin S, Camoglio L, et al. Interleukin-1signaling is essential forhost defense during murine pulmonary tuberculosis. J Infect Dis,2000;182:902-908.
[32] Law K, Weiden M, Harkin T, et al. Increased release of interleukin-1beta,interleukin-6, and tumor necrosis factor-alpha by bronchoalveolar cells lavaged frominvolved sites in pulmonary tuberculosis. Am J Respir Crit CareMed,1996;153:799-804.
[33] Crisafulli E, Menéndez R, Huerta A,et al. Systemic inflammatory pattern of patientswith community-acquired pneumonia with and without COPD.Chest,2013,143(4):1009-1017.
[34]李红,唐神结.肺结核患者外周血sIL-2R、TNF-ɑ、IFN-γ、IL-6的检测及意义.中国防痨杂志，2011，33（1）:57-60.
[35] Tsao TC, Huang CC, Chiou WK, et al. Levels of interferon-gamma and interleukin-2receptor-alpha for bronchoalveolar lavage fluid and serum were correlated withclinical grade and treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis,2002,6(8):720-727.
[36] Mustafa AS, Al-Saidi F, El-Shamy AS, et al. Cytokines in response to proteinspredicted in genomic regions of difference of Mycobacterium tuberculosis. MicrobiolImmunol,2011,55(4):267-278.
[37] Flynn J. Immunology of tuberculosis and implications in vaccine development.Tuberculosis2004;4:93-101.
[38] Bai X, Wilson SE, Chmura K, et al. Morphometric analysis of Th(1) and Th(2)cytokine expression in human pulmonary tuberculosis. Tuberculosis2004;84:375-385.
[39] Diedrich CR, Mattila JT,Flynn JL. Monocyte-derived IL-5reduces TNF productionby Mycobacterium tuberculosis-specific CD4T cells during SIV/M.tuberculosis coinfection. J Immunol,2013,190(12):6320-6328.
[40] Kumar NP, Sridhar R, Banurekha VV, et al. Type2diabetes mellitus coincident withpulmonary tuberculosis is associated with heightened systemic type1, type17, andother proinflammatory cytokines. Ann Am Thorac Soc,2013,10(5):441-449.
[41] Cozmei C, Constantinescu D, Carasevici E,et al. Th1and Th2cytokine response inpatients with pulmonary tuberculosis and health care workers occupationally exposedto M. tuberculosis. Rev Med Chir Soc Med Nat Iasi,2007,111(3):702-709.
[42] Mat Z, Grensemann B, Yakin Y,et al. Effect of lipoteichoic acid on IL-2and IL-5release from T lymphocytes in asthma and COPD. Int Immunopharmacol,2012,13(3):284-291.
[43] Mattos AM, Almeida Cde S, Franken KL. Increased IgG1, IFN-gamma, TNF-alphaand IL-6responses to Mycobacterium tuberculosis antigens in patients withtuberculosis are lower after chemotherapy. Int Immunol,2010,22(9):775-782.
[44] Donaldson GC, Seemungal TA, Patel IS, et al. Airway and systemic inflammation anddecline in lung function in patients with COPD. Chest,2005,128:1995–2004.
[45] He JQ, Foreman MG, Shumansky K, et al. Associations of IL-6polymorphisms withlung function decline and COPD. Thorax,2009,64:698–704.
[46] Karadag F, Karul AB, Cildag O,et al. Biomarkers of systemic inflammation in stableand exacerbation phases of COPD. Lung,2008,186:403–409.
[47] Yende S, Waterer GW, Tolley EA, et al. Inflammatory markers are associated withventilatory limitation and muscle dysfunction in obstructive lung disease in wellfunctioning elderly subjects. Thorax,2006,61:10-16.
[48] Attaran D, Lari SM, Towhidi M, et al. Interleukin-6and airflow limitation in chemicalwarfare patients with chronic obstructive pulmonary disease. International Journal ofChronic Obstructive Pulmonary Disease,2010,5:335-340.
[49] Djoba Siawaya JF, Beyers N, et al. Differential cytokine secretion and early treatmentresponse in patients with pulmonary tuberculosis. Clin Exp Immunol,2009,156:69-77.
[50] Kaufmann SHE. How can immunology contribute to the control of tuberculosis?Nature Reviews Immunology,2001,1(1):20–30.
[51] Sutherland JS, de Jong BC, Jeffries DJ, et al. Production of TNF-alpha, IL-12(p40)and IL-17can discriminate between active TB disease and latent infection in a WestAfrican cohort. PLoS One,2010,5(8): e12365.
[52] Bekker, L G, Moreira A L, Bergtold A, et al. Immunopathologic effects of tumornecrosis factor alpha in murine mycobacterial infection are dose dependent. InfectImmun,2000,68:6954–6961.
[53] Hodge G, Nairn J, Holmes M, et al. Increased intracellular T helper1proinflammatory cytokineproduction in peripheral blood, bronchoalveolar lavageandintraepithelial T cells of COPD subjects. Clinical and Experimental Immunology,2007,150:22-29.
[54] Lago PM, Boéchat N, Migueis DP, et al. Interleukin-10and interferon-gammapatterns during tuberculosis treatment: possible association with recurrence. Int JTuberc Lung Dis,2012,16(5):656-659.
[55] Ray JC, Wang J, Chan J, et al. The timing of TNF and IFN-gamma signaling affectsmacrophage activation strategies during Mycobacterium tuberculosis infection. JTheor Biol,2008,252(1):24-38.
[56] Kellar KL, Gehrke J, Weis SE, et al. Multiple cytokines are released when blood frompatients with tuberculosis is stimulated with Mycobacterium tuberculosis antigens.PLoS One,2011,6(11): e26545.
[57] Goletti D, Raja A, Ahamed-Kabeer BS, et al. IFN-gamma, but not IP-10, MCP-2orIL-2response to RD1selected peptides associates to active tuberculosis. The Journalof Infection,2010,61(2):133-143.
[58] Jurado JO, Pasquinelli V, Alvarez IB, et al. IL-17and IFN-γ expression inlymphocytes from patients with active tuberculosis correlates with the severity of thedisease. J Leukoc Biol,2012,91(6):991-1002.
[59]张少俊，肖和平.复治肺结核与初治结核病患者外周血T细胞亚群等的变化及其意义.中华结核和呼吸杂志，2011，34(12):884-887.
[60] Aaron SD, Angel JB, Lunau M, et al. Granulocyte inflammatory markers and airwayinfection during acute exacerbation of chronic obstructive pulmonary disease. Am JRespir Crit Care Med,2001,163:349-355.
[61] Bucchioni E, Kharitonov SA, Allegra L, et al. High levels of interleukin-6in theexhaled breath condensate of patients with COPD. Respir Med,2003,97:1299-1302.
[62] Soler N, Ewig S, Torres A, et al. Airway inflammation and bronchial microbialpatterns in patients with stable COPD. Eur Respir J,1999,14(5):1015-1022.
[63] Herfs M, Hubert P, Poirrier AL, et al. Proinflammatory cytokines induce bronchialhyperplasia and squamous metaplasia in smokers: implications for chronic obstructivepulmonary disease therapy. Am J Respir Cell Mol Biol,2012,47(1):67-79.
[64] Lam, KH, Jiang, CQ, Jordan, RE, et al. Prior TB, Smoking, and Airflow Obstruction:A Cross-Sectional Analysis of the Guangzhou Biobank Cohort Study. Chest,2010,137:593-600.
[65] Menezes AMB, Hallal PC., Perez-Padilla R., et al. Tuberculosis and AirflowObstruction: evidence from the PLATINO study in Latin America. EuropeanRespiratory Journal,2007,30:1180-1185.
[66] Chakrabarti B, Calverley PMA, Davies PDO. Tuberculosis and its incidence, specialnature,and relationship with chronic obstructive pulmonary disease. InternationalJournal of COPD,2007,2(3):263-272.
[1] Calverley PM, Walker P.Chronic obstructive pulmonary disease. Lancet,2003,362:1053–1061.
[2] WHO. Global tuberculosis report2013. WHO/HTM/TB/2013.11. Geneva,Switzerland: WHO,2013.
[3] WHO. Global tuberculosis report2012. WHO/HTM/TB/2012.6. Geneva, Switzerland:WHO,2012.
[4]全国结核病流行病学抽样调查技术指导组.第四次全国结核病流行病学抽样调查报告.中华结核和呼吸杂志，2002，25(1):3-7.
[5]全国第五次结核病流行病学抽样调查技术指导组.2010年全国第五次结核病流行病学抽样调查报告.中国防痨杂志，2012，34（8）：485-508.
[6]唐神结.结核病免疫研究进展.国外医学内科学分册，2002，29(9):369.
[7]唐神结，肖和平,范以虎等.肺结核患者血清前炎细胞因子及其受体的变化.中华结核和呼吸杂志，2002，25（6）:325.
[8]唐神结，肖和平，胡家瑛等.复治肺结核患者外周血中活化T淋巴细胞的变化及其意义.中华结核和呼吸杂志，2007，30：.707-708.
[9] Inghammar M, Ekbom A, Engstr m G, et al. COPD and the Risk of Tuberculosis-APopulation-Based Cohort Study. PLoSONE2010,5(4): e10138.
[10] Liu CH, Yang N, Wang Q, et al.(), Risk factors associated withfluoroquinolone-resistant tuberculosis in a Beijing tuberculosis referral hospital.Respirology,2011,16:918–925.
[11]郑立学，胡忠义.结核病体液免疫检测进展.临床肺科杂志，2000,5(2):86-88.
[12] Abebe F, Bjune G. The protective role of antibody responses during Mycobacteriumtuberculosis infection. The Journal of Translational Immunology,2009,157:235-243.
[13] de Valliere S, Abate G Blazevic A et al. Enhancement of cellmediated immunity byantimycobacterial antibodies. Infect Immun2005;73:6711-20.
[14] Relijic R, Ivanyi J. A case for passive immunoprophylaxis against tuberculosis.Lancet Infect Dis2006;6:813-18.
[15] Pethe K, Alonso S, Biet F et al. The heparin-binding hemagglutinin of M. tuberculosisis required for extrapulmonary dissemination.Nature2001;412:190-4.
[16] Chambers MA, Gavier-Widen D, Hewinson RG. Antibody bound to the surfaceantigen MPB83of Mycobacterium bovis enhances survival against high dose and lowdose challenge. FEMS Immunol Med Microbiol2004;41:93-100.
[17] Shen CY, Hsieh SC, Yu CL, et al. Autoantibody prevalence in active tuberculosis:reactive or pathognomonic? BMJ Open,2013,3(7): pii: e002665.
[18] Boes M. Role of natural and immune IgM antibodies in immune responses. MolImmunol,2000,37:1141-1149.
[19] Le Moigne V, Le Moigne D, Mahana W. Antibody response to Mycobacteriumtuberculosis p27-PPE36antigen in sera of pulmonary tuberculosis patients.Tuberculosis,2013,93(2):189-191.
[20] Glatman-Freedman A. The role of antibody-mediated immunity in defense againstMycobacterium tuberculosis: advances toward a novel vaccine strategy. Tuberculosis(Edinb)2006,86:191-97.
[21] Reljic R. Clark SO, Williams A, et al. Intranasal IFNgamma extends passive IgAantibody protection of mice against Mycobacterium tuberculosis lung infection. ClinExp Immunol,2006,143:467-473.
[22] Mattos AM,Almeida CdeS, Franken KL, et al. Increased IgG1, IFN-gamma,TNF-alpha and IL-6responses to Mycobacterium tuberculosis antigens in patientswith tuberculosis are lower after chemotherapy. International Immunology,2010,22(9):775-782.
[23]佟玉平，李艳丽和张春梅.肺结核病人应用肺活素治疗前后的细胞因子及体液免疫水平检测.黑龙江医学，2008，28（5）：377.
[24] Zu iga J, Torres-García D, Santos-Mendoza T, et al. Cellular and humoralmechanisms involved in the control of tuberculosis. Clinical and developmentalImmunology,2012,2012:193923.
[25]匡铁吉，宋萍，金关甫，等.住院肺结核患者体液免疫水平的变化及其临床意义.军医进修学院学报，1996，17（3）：178-181.
[26] Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of chronic obstructivepulmonary disease: insights from recent research. Proc Am Thorac Soc,2007,4(7):512-521.
[27] Musher DM, Groover JE, Rowand JM, et al. Antibody to capsular polysaccharides ofstreptococcus pneumoniae: prevalence, persistence, and response to revaccination.Clin lnfect Dis,1993,17(3):66-73.
[28]黄琛，胡轶，汤汉红.COPD患者肺功能与血清免疫球蛋白及C反应蛋白的关系.医学新知杂志，2008，18（2）：111-112.
[29] Feghali-Bostwick CA, Gadgil AS, Otterbein LE,et al. Autoantibodies in Patients withChronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med,2008:177(2):156-163.
[30] Brandsma CA, Kerstjens HA, van Geffen WH, et al. Differential switching to IgG andIgA in active smoking COPD patients and healthy controls. Eur Respir J,2012,40(2):313-321.
[31] Brandsma C,Hylkema MN,Geerlings M,et al. Increased levels of (class switched)memory B cells in peripheral blood of current smokers. RespiratoryResearch,2009,10:108-118.
[32] Millares L, Marin A, Garcia-Aymerich J, et al. Specific IgA and metalloproteinaseactivity in bronchial secretions from stable chronic obstructive pulmonary diseasepatients colonized by Haemophilus influenza. Respiratory Research,2012,13:113-123.
[33]沈芸，唐神结，孙华等．肺结核合并慢性阻塞性肺疾病患者免疫功能的变化及意义．同济大学学报（医学版）．2012，33（1）：53-58．
[34]朱友生，唐神结.巨噬细胞在抗结核免疫中的作用及其研究进展.中国防痨杂志，2004，26（3）：173-175.
[35]唐神结，肖和平.细胞因子网络与结核病.中华结核和呼吸杂志2001，24（9）：571-574.
[36] Kim W D, Kim W S, Koh Y. Abnormal peripheral bloodT-lymphocyte subsets in a subgroup of patients with COPD. Chest.,2002,122(2):437-444.
[37] Shirai T, Suda T, Inui N. Correlation between peripheral bloodT-cell profiles and clinical and inflammatory parameters in stableCOPD. Allergol Int,2010,59(1):75-82.
[38]汤其岭．COPD患者治疗前后血清SOD和T淋巴细胞亚群检测的临床意义．淮海医药，2008，26（6）：486-487．
[39]夏晓东，刘道候，徐永安，等.慢性阻塞性肺疾病患者T细胞亚群动态变化.浙江实用医学，2008,13（2）:85-86.
[40] Malin Inghammar, M., Anders Ekbom, A., Engstr m, G., et al. COPD and the Risk ofTuberculosis-A Population-Based Cohort Study. PLoS One,2010,5(4): e10138.
[41] Shenjie Tang, Haiyan Cui, Lan Yao,et al.Increased Cytokines Response in Patientswith Tuberculosis Complicated with Chronic Obstructive Pulmonary Disease. PLOSONE,2013,8(4):e62385.
[42] Zahran WA，Ghonaim MM, Koura BA, EI-Banna H, Ali SM, EI-Sheikh N.Humannatural killer T cells(NKT),NK and T cells in pulmonary tuberculosis:potentialindicators for disease activity and prognosis. Egypt J Immunol.2006,13(1):67-78.
[43] Kulpraneet M, Sukwit S, Sumransurp K, et al. Cytokine production in NK and NKTcells from Mycobacterium tuberculosis infected patients. Southeast Asian J Trop MedPublic Health,2007,38(2):370-375.
[44] Leung W L,Law K L, Leung V S et al. Comparison of intracellular cytokine flowcytometry and an enzyme immunoassay for evaluat ion of cellularimmune response toactive tuberculosis. Clin Vaccine Immunol,2009;16(3):344-351.
[45]翟慧,刘一典,唐神结,等.肺结核患者外周血NKT细胞、NK细胞、T淋巴细胞亚群的变化及意义.同济大学学报(医学版),2010;31(5):42-46.
[46]孙巍，杨永辉，李登瑞，等.NKT细胞、NK细胞和T细胞亚群在活动性肺结核患者外周血的表达及意义.中国免疫杂志，2011，27（11）：1030-1034.
[47]张青，肖和平． T细胞、NKT细胞和NK细胞在结核病诊断中的意义探讨．中国防痨杂志，2010，32(5):267-271．
[48]邱晓静，王兆华，王健，等.肺结核患者外周血NK细胞数量和胞内杀伤分子的变化.蚌埠医学院学报，2012，37（10）：1141-1144.
[49]周晓映，于红艳，王惠青，等.2型糖尿病合并肺结核患者T淋巴细胞亚群和NK细胞的变化及其临床意义.疑难病杂志，2008，7（11）：666-668.
[50]王心静，杨秉芬，原艳明，等.初治菌阳肺结核患者外周血NK细胞比例显著下降.免疫学杂志，2013，29（8）：677-680.
[51] Portevin D, Via LE, Eum S, et al. Natural killer cells are recruited during pulmonarytuberculosis and their ex vivo responses to mycobacteria vary between healthy humandonors in association with KIR haplotype. Cell Microbiol,2012,14(11):1734-1744.
[52] Vankayalapati R, Wizel B, Weis SE, et al. The NKp46receptor contributes to NK celllysis of mononuclear phagocytes infected with an intracellular bacterium. JImmunol,2002,168(7):3451-3457.
[53]付笑迎,李丽,李琴,等.结核性胸液中NK细胞的亚群及表型功能特征分析.免疫学杂志,2012,28(8):691-694.
[54]黄美健，冷报浪，梁斌，等.慢性阻塞性肺疾病不同病期细胞免疫功能的临床研究.浙江实用医学,2004,6（8）:664-665.
[55]傅佩芳，殷少军，颜正茂，等。慢性阻塞性肺疾病患者与免疫功能关系的临床研究。中国现代医学杂志，2008，18（3）：338-340.
[56]王娜，夏婧.慢性阻塞性肺疾病患者免疫功能的变化.贵州医药，2011，35（7）:593-595.
[57]张蔚，江山平，吕志强，等.慢性阻塞性肺疾病患者外周血T淋巴细胞亚群和NK细胞的动态变化.中山大学学报（医学科学版），2005，3S：115-116.
[58] Mueller H, Detjen AK, Schuck SD, et al. Mycobacterium tuberculosis-specific CD4+,IFNgamma+, and TNFalpha+multifunctional memory T cells coexpress GM-CSF.Cytokine,2008,43(2):143-148.
[59] Küpeli E, Karnak D, Beder S, et al. Diagnostic accuracy of cytokine levels(TNF-alpha, IL-2and IFN-gamma) in bronchoalveolar lavage fluid of smear-negativepulmonary tuberculosis patients. Respiration,2008,75(1):73-78.
[60] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scand JImmunol,2012,75(6):623-632.
[61] Shitrit D, Izbicki G, Bar-Gil Shitrit A, et al. Role of soluble interleukin-2receptorlevels in patients with latent tuberculosis. Lung,2006,184(1):21-24.
[62] Barnes PJ. The Cytokine Network in Chronic Obstructive Pulmonary Disease. Am JRespir Cell Mol Biol,2009,41:631–638.
[63] GadgilA, Zhu X, Sciurba FC, et al. Altered T-cell phenotypes in chronic obstructivepulmonary disease. Proc Am Thorac Soc,2006,3(6):487-488.
[64] Katti MK. Assessment of serum IL-1, IL-2and IFN-γ levels in untreated pulmonarytuberculosis patients: role in pathogenesis. Archives of Medical Research,2011,42(3):199-201.
[65] Crisafulli E, Menéndez R, Huerta A,et al. Systemic inflammatory pattern of patientswith community-acquired pneumonia with and without COPD. Chest,2013,143(4):1009-1017.
[66]李红,唐神结.肺结核患者外周血sIL-2R、TNF-ɑ、IFN-γ、IL-6的检测及意义.中国防痨杂志，2011，33（1）:57-60.
[67] Tsao TC, Huang CC, Chiou WK, et al. Levels of interferon-gamma and interleukin-2receptor-alpha for bronchoalveolar lavage fluid and serum were correlated withclinical grade and treatment of pulmonary tuberculosis. Int J Tuberc Lung Dis,2002,6(8):720-727.
[68] Mustafa AS, Al-Saidi F, El-Shamy AS, et al. Cytokines in response to proteinspredicted in genomic regions of difference of Mycobacterium tuberculosis. MicrobiolImmunol,2011,55(4):267-278.
[69] Al-Attiyah R, El-Shazly A, Mustafa AS. Comparative analysis of spontaneous andmycobacterial antigen-induced secretion of Th1, Th2and pro-inflammatory cytokinesby peripheral blood mononuclear cells of tuberculosis patients. Scandinavian Journalof Immunology,2012,75(6):623-632.
[70] Diedrich CR, Mattila JT,Flynn JL. Monocyte-derived IL-5reduces TNF productionby Mycobacterium tuberculosis-specific CD4T cells during SIV/M.tuberculosis coinfection. J Immunol,2013,190(12):6320-6328.
[71] Kumar NP, Sridhar R, Banurekha VV, et al. Type2diabetes mellitus coincident withpulmonary tuberculosis is associated with heightened systemic type1, type17, andother proinflammatory cytokines. Ann Am Thorac Soc,2013,10(5):441-449.
[72] Cozmei C, Constantinescu D, Carasevici E,et al. Th1and Th2cytokine response inpatients with pulmonary tuberculosis and health care workers occupationally exposedto M. tuberculosis. Rev Med Chir Soc Med Nat Iasi,2007,111(3):702-709.
[73] Mat Z, Grensemann B, Yakin Y,et al. Effect of lipoteichoic acid on IL-2and IL-5release from T lymphocytes in asthma and COPD. Int Immunopharmacol,2012,13(3):284-291.
[74] Mattos AM, Almeida CS, Franken KL. Increased IgG1, IFN-gamma, TNF-alpha andIL-6responses to Mycobacterium tuberculosis antigens in patients with tuberculosisare lower after chemotherapy. Int Immunol,2010,22(9):775-782.
[75] He JQ, Foreman MG, Shumansky K, et al. Associations of IL-6polymorphisms withlung function decline and COPD. Thorax,2009,64:698–704.
[76] Karadag F, Karul AB, Cildag O,et al. Biomarkers of systemic inflammation in stableand exacerbation phases of COPD. Lung,2008,186:403–409.
[77] Yende S, Waterer GW, Tolley EA, et al. Inflammatory markers are associated withventilatory limitation and muscle dysfunction in obstructive lung disease in wellfunctioning elderly subjects. Thorax,2006,61:10-16.
[78] Attaran D, Lari SM, Towhidi M, et al. Interleukin-6and airflow limitation in chemicalwarfare patients with chronic obstructive pulmonary disease. International Journal ofChronic Obstructive Pulmonary Disease,2010,5:335-340.
[79] Djoba Siawaya JF, Beyers N, et al. Differential cytokine secretion and early treatmentresponse in patients with pulmonary tuberculosis. Clin Exp Immunol,2009,156:69-77.
[80] Nemeth J, Winkler HM, Boeck L, et al. Specific cytokine patterns of pulmonarytuberculosis in Central Africa. Clin Immunol,2011,138(1):50-59.
[81] Sutherland JS, de Jong BC, Jeffries DJ, et al. Production of TNF-alpha, IL-12(p40)and IL-17can discriminate between active TB disease and latent infection in a WestAfrican cohort. PLoS One,2010,5(8): e12365.
[82] Moermans C, Heinen V, Nguyen M, et al. Local and systemic cellular inflammationand cytokine release in chronic obstructive pulmonary disease. Cytokine,2011,56(2):298-304.
[83] Hodge G, Nairn J, Holmes M, et al. Increased intracellular T helper1proinflammatory cytokineproduction in peripheral blood, bronchoalveolar lavageandintraepithelial T cells of COPD subjects. Clinical and Experimental Immunology,2007,150:22-29.
[84] Lago PM, Boéchat N, Migueis DP, et al. Interleukin-10and interferon-gammapatterns during tuberculosis treatment: possible association with recurrence. Int JTuberc Lung Dis,2012,16(5):656-659.
[85] Ray JC, Wang J, Chan J, et al. The timing of TNF and IFN-gamma signaling affectsmacrophage activation strategies during Mycobacterium tuberculosis infection. JTheor Biol,2008,252(1):24-38.
[86] Kellar KL, Gehrke J, Weis SE, et al. Multiple cytokines are released when blood frompatients with tuberculosis is stimulated with Mycobacterium tuberculosis antigens.PLoS One,2011,6(11): e26545.
[87] Goletti D, Raja A, Ahamed-Kabeer BS, et al. IFN-gamma, but not IP-10, MCP-2orIL-2response to RD1selected peptides associates to active tuberculosis. The Journalof Infection,2010,61(2):133-143.