药物滥用者机体免疫功能损伤机制探讨

WedetectedtheperipheralbloodindexesofsubgroupsofThcells，transformationrateoflymphocytes，IgA，IgM，IgG，IgE，complimentC３，C４，IL－１，IL－６，TNFandNOin５０drugabusersandsuggestedthemechanismofimmunefunctioninjuryinthem．１Subjectsandmethods１．１SubjectsThetestgroupcomprisedof５０confirmeddrugabusersadmittedbytheDongpolingAbstinenceCenterofZhanjiangPublicSafetyBureauincluding３０malesand２０females，aging１８～３７yearsmeanly（２６．４０±４．６８）years．Allofthemweredrugabuse…     

创伤患者血清免疫球蛋白、补体和C-反应蛋白的变化

目的：探讨创伤患者免疫功能的变化及临床意义。方法：３０例创伤术后患者分为创伤组及创伤并发症组,分别在术后第１,７及１４日测定外周血清免疫球蛋白ＩｇＧ,ＩｇＡ,ＩｇＭ,补体Ｃ３,Ｃ４及Ｃ－反应蛋白（ＣＲＰ）,并与正常对照组进行对比分析。结果：创伤组及创伤并发症组的免疫球蛋白,补体均在术后第１日明显降低,而ＣＲＰ明显升高。     

Severe injury triggers antigen-specific T-helper cell dysfunction.

Although it is established that post-injury immune dysfunction involves alterations in T-cell function, the effects of injury on T-cell function in vivo are poorly understood. This study uses a mouse injury model and an antigen immunization approach to investigate the influence of injury on antigen-specific T-helper cell function. We report here that injury triggered a significant reduction in antigen-specific T-helper-1 (Th1)-dependent IgG2a antibody formation, while IgM, IgG1, and IgE production was unchanged. In addition, injury caused a reduction in cytokine production (IL-2, IFNgamma and IL-10) by antigen-stimulated T-cells. We also demonstrate that interleukin 12 (IL-12), a cytokine that promotes Th1 cell differentiation, restored IgG2a antibody formation and corrected the injury-induced reduction in antigen-stimulated cytokine production. Taken together, these findings indicate that severe injury induces a dramatic reduction in Th1 cell function in vivo and suggest that therapies designed to restore Th1 cell function may be beneficial to the injured host.     

急性心肌梗死合并多器官功能障碍综合征患者血清免疫球蛋白、补体和C-反应蛋白的变化

目的:探讨急性心肌梗死(AMI)合并多器官功能障碍综合征(MODS)患者免疫功能的变化及临床意义。方法:81例AMI患者分为AMI(A)组及AMI合并MODS(B)组,分别在病后第1、7及14 d测定免疫球蛋白IgG、IgA、IgM,补体C3、C4及C-反应蛋白(CRP),并与正常对照组进行对比分析。再根据溶栓情况将81例AMI患者分为常规治疗组、溶栓未通组、溶栓再通组,溶栓后2 h再测定上述指标。结果:两组免疫球蛋白、补体均在病后第1 d明显降低,而CRP明显升高(P<0.05)。A组在病后第7 d免疫球蛋白、补体及CRP均基本恢复正常(P>0.05);而B组在病后第7 d IgG、IgA仍明显低于正常,而CRP更为升高(P<0.01),A组在病后第14 d免疫球蛋白及补体均明显高于正常(P<0.01),而B组免疫球蛋白稍高于正常;CRP下降至接近正常。溶栓再通组免疫球蛋白、补体均明显高于溶栓未通组和常规治疗组:溶栓再通组CRP明显低于溶栓未通组和常规治疗组。结论:AMI后早期免疫功能处于抑制状态,动态观察免疫球蛋白、补体及CRP在血清中的变化可作为AMI患者病情观察的客观指标。     

Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells

The effect of interleukin 8 (IL-8) on IL-4-induced immunoglobulin E (IgE) production was studied. IL-4 induced IgE and IgG4 production by tonsillar mononuclear cells (MNC) without affecting IgM, IgG1, IgA, IgG2, or IgG3 production. IL-8 inhibited IL-4-induced IgE and IgG4 production, whereas it had no effect on IgM, IgG1, IgA, IgG2, and IgG3 production. The inhibitory effect by IL-8 was specific, since it was blocked by anti-IL-8 mAb, but not by control IgG1. Although interferon gamma (IFN-gamma) also inhibited IgE and IgG4 production by MNC stimulated with IL-4, the inhibitory effect of IL-8 was not mediated by IFN-gamma, since the IL-8-induced inhibition could not be blocked by anti-IFN-gamma. Furthermore, anti-IL-8 mAb had no effect on IFN-gamma-induced inhibition. Moreover, addition of IL-5 or IL-6 did not reverse IL-8-induced inhibition of IgE production. In contrast to these observations with MNC, IL-4 failed to induce IgE and IgG4 production by purified B cells. However, combined treatment of purified B cells cells with IL-4 and anti-CD40 antibody resulted in IgE but not IgG4 production. IL-8 inhibited this IgE production without affecting IgM, IgG1, IgG2, IgG3, IgG4, or IgA production, whereas IFN-gamma, IFN-alpha, or prostaglandin E2 (PGE2) failed to do so. These results indicate that IL-8 antagonizes IL-4-induced IgE production by directly affecting B cells through a specific mechanism that is different from IFN-gamma, IFN-alpha, or PGE2.     

Immunoglobulins and IgG subclasses in children following severe head injury

Objective To study immunoglobulin production after severe blunt head trauma in children.Design Serum for IgG, IgM, IgA, IgE, and IgG subclasses were drawn from 10 children admitted with severe head injury (ISS 31.2, GCS 5.4) on day 1, 7, 14 and 21 after injury.Results 5 of the 10 patients developed infection between 7 and 14 days and 2 died of complications of pneumonia. On day 1, IgM levels averaged 95.6% of the mean of the age-specific normal controls. By day 7, IgM levels averaged 383% (p<0.01). While all patients were within the age-specific normal range (± 2 SD) on day 1, 7 of 10 patients were above the normal range by day 7. There was no difference in IgM levels between infected and non-infected patients. Five patients were below the age-specific normal range for IgG on day 1, with 3 still low on day 7. By day 21, IgG levels averaged 141% of the mean of the age-specific normal controls. IgG subclasses followed a pattern similar to total IgG levels. Marked increases in IgE were seen in 3 patients.Conclusions IgM levels increased dramatically in all patients within seven days of the injury. While 50% of these children had a deficit of IgG in the first week, total IgG and IgA levels increased after injury, but not as rapidly as IgM levels. Unlike pediatric burn patients, there is no persistent hypogammaglobulinemia following severe blunt trauma in children.Supported by a grant from Sandoz Pharmaceuticals, East Hanover, New Jersey, USA     

急性有机磷农药中毒患者体液免疫功能的变化及意义

目的：探讨急性有机磷农药中毒患者体液免疫功能的变化及意义。方法：采用速率散射比浊法检测４５例急性有机磷农药中毒患者及３０例正常人血清ＩｇＧ、ＩｇＡ、ＩｇＭ、Ｃ３、Ｃ４水平，并对其中２５例患者作了动态观测。结果：急性有机磷农药中毒患者血清ＩｇＡ高于正常对照组（Ｐ＜０．００１）；中毒后ＩｇＡ开始升高，中毒第３日和第７日均明显高于正常对照组（Ｐ＜０．０５和Ｐ＜０．００１）；ＩｇＧ、ＩｇＭ、Ｃ３、Ｃ４与正常对照组比较均无显著性差异（Ｐ均＞０．０５）。结论：急性有机磷农药中毒患者粘膜局部免疫功能增强，并提示胆碱能神经功能亢进     

Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor

During antigen-induced immune responses, human B cells switch isotype from immunoglobulin M (IgM)-IgD to IgG1-4, IgA1-2, or IgE. In the human, no cytokines have yet been demonstrated to act as switch factors for IgG1, IgG2, and IgG3. In this paper, we report that in response to interleukin 10 (IL-10), anti-CD40 activated tonsillar surface IgD+ (sIgD+) B cells are induced to secrete large amounts of IgM, IgG1, and IgG3 but neither IgG2 nor IgG4. Cord blood purified B cells and lymphocytes from Hyper-IgM patients also produced IgG1 and IgG3 after culture with anti-CD40 and IL-10. In contrast, sIgD- isotype-committed B cells produce IgG1, IgG2, and IgG3 when activated through CD40 in the presence of IL-10. Thus, in addition to its growth-promoting and differentiating activities on human B cells, IL-10 may represent a switch factor for IgG1 and IgG3.     

紫外线照射充氧自血回输对白塞氏综合征患者免疫指标及粘附分子的影响

目的 探讨紫外线照射充氧自血回输（UBIO）治疗白塞氏综合征（BS）的作用、疗效及机制。方法 动态观察21例BS患者UBIO治疗前后CD3、CD4、CD8、IgG、IgA、IgM、C3及粘附分子（CD44）变化,以药物治疗10例BS患者为药物对照组,并作疗效比较。结果 UBIO前BS患者的CD3、CD4、CD8、IgG、IgA、IgM、C3均显著低于健康人群,经UBIO作用后上述指标发生了显著性变化,总有效率UBIO组为95%（20/21）,药物组为70%（7/10）。结论 BS患者存在着体液及细胞免疫功能失调,UBIO具有调节免疫功能及粘附分子的作用。     

Histamine selectively enhances human immunoglobulin E (IgE) and IgG4 production induced by anti-CD58 monoclonal antibody

We studied the effects of histamine on human immunoglobulin (IgE) and IgG4 production. Histamine selectively enhanced IgE and IgG4 production in purified surface IgE and IgG4 negative (sIgE-sIgG4-) B cells from normal donors stimulated with interleukin (IL)-4 plus anti-CD58 or IL- 13 plus anti-CD58 monoclonal antibody (mAb) without affecting production of IgG1, IgG2, IgG3, IgM, IgA1, or IgA2. In cultures with IL- 4 plus anti-CD58 mAb, histamine-induced enhancement of IgE and IgG4 production was specifically blocked by thioperamide (H3 receptor antagonist), and was inhibited by anti-IL-10 antibody (Ab). In contrast, in cultures with IL-13 plus anti-CD58 mAb, histamine-induced enhancement was blocked by dimaprit (H1 receptor antagonist), and was inhibited by anti-IL-6 mAb. Histamine also enhanced IgE and IgG4 production by in vivo-generated sIgE+ and sIgG4+ B cells, respectively, from atopic patients; enhancement was blocked by dimaprit and thioperamide, and was inhibited by anti-IL-6 mAb and anti-IL-10 Ab. In sIgE-sIgG4- B cells, IL-4 plus anti-CD58 mAb induced IL-10 production and IL-10 receptor expression, whereas IL-13 plus anti-CD58 mAb induced IL-6 production and IL-6 receptor expression. Histamine increased IL-10 and IL-6 production without affecting IL-10 and IL-6 receptor expression, in cultures with IL-4 plus anti-CD58 mAb and with IL-13 plus anti-CD58 mAb, respectively, which was blocked by thioperamide and dimaprit, respectively. In contrast, sIgE+ and sIgG4+ B cells spontaneously produced both IL-6 and IL-10 and constitutively expressed IL-6 and IL-10 receptors, and histamine increased IL-6 and IL-10 production without affecting IL-6 or IL-10 receptor expression, which was blocked by thioperamide and dimaprit. These results indicate that histamine enhanced IgE and IgG4 production by increasing endogenous IL- 6 and IL-10 production via H1 and H3 receptors, respectively.     

Helper activity for immunoglobulin synthesis of T helper type 1 (Th1) and Th2 human T cell clones: the help of Th1 clones is limited by their cytolytic capacity

A large number of CD4+ human T helper type 1 (Th1) clones specific for purified protein derivative and of Th2 clones specific for the excretory/secretory antigen of Toxocara canis, derived from the same individuals, were analyzed for both cytotoxic capacity and helper function for immunoglobulin (Ig) synthesis. The great majority of Th1, but only a minority of Th2 clones exhibited cytolytic activity. All Th2 (noncytolytic) clones induced IgM, IgG, IgA, and IgE synthesis by autologous B cells in the presence of the specific antigen, and the degree of response was proportional to the number of Th2 cells added to B cells. Under the same experimental conditions, Th1 (cytolytic) clones provided helper function for IgM, IgG, and IgA, but not IgE, synthesis with a peak response at 1:1 T/B cell ratio. At higher T/B cell ratios, a strong decrease of Ig synthesis was observed. All Th1 clones lysed Epstein-Barr virus transformed autologous B cells pulsed with the specific antigen. The decrease of Ig production at high T/B cell ratios correlated with the lytic activity of Th1 clones against autologous antigen-presenting B cell targets. These data suggest that Th1 differ from Th2 human T cell clones not only for their profile of cytokine secretion, but also for cytolytic potential and mode of help for B cell Ig synthesis.     

Oral but Not Parenteral Interleukin (IL)-12 Redirects T Helper 2 (Th2)-type Responses to an Oral Vaccine Without Altering Mucosal IgA Responses

Our past studies have shown that the mucosal adjuvant cholera toxin (CT) induces T helper type 2 (Th2) responses with systemic IgG1, IgE and mucosal secretory IgA (S-IgA) antibodies (Abs). In this study, recombinant murine IL-12 (rmIL-12) was given either parenterally or orally to mice orally immunized with tetanus toxoid (TT) and CT to determine whether this cytokine could redirect the CT-induced Th2-type responses and what effect this shift would have on S-IgA Ab responses. Intraperitoneal administration of rmIL-12 shifted TT-specific responses toward Th1-type and resulted in CD4⁺ T cells producing IFN-γ and IL-2 with markedly reduced levels of Th2-type cytokines. This cytokine profile was accompanied by increased delayed-type hypersensitivity (DTH) and shifts in serum IgG1 to IgG2a and IgG3 anti-TT Ab responses. Further, serum IgE and S-IgA Ab responses were markedly reduced by parenteral IL-12. When IL-12 complexed to liposomes was given orally both shifts to IgG2a and IgG3 and low IgE Abs again occurred concomitant with enhanced serum IFN-γ and DTH responses. Interestingly, oral rmIL-12 did not result in significant levels of serum IL-12 nor altered S-IgA Ab responses and resulted in higher levels of some Th2-type cytokines both in vitro and in vivo when compared with parenteral IL-12. Our results show that the shifts in systemic immune responses with intact S-IgA Abs which occur after oral delivery of IL-12-liposomes are due to cytokine effects in the Peyer's patches and suggest new strategies for the targeted manipulation of Th1- and Th2-type responses to mucosal vaccines.     

Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures

Although it has been established that IL-4 enhances both IgG1 and IgE secretion in LPS-stimulated B cell cultures, these studies failed to determine whether IL-4 preferentially induces isotype switching or preferentially allows for the maturation of precommitted precursor cells. To distinguish between these possibilities, it is necessary to ascertain the effect of IL-4 on the isotypes secreted by individual precursor cells during clonal expansion. Therefore, clonal cultures of B cells stimulated with a Th2 helper cell line specific for rabbit Ig and rabbit anti-mouse IgM were established. The majority of B cells are capable of undergoing clonal expansion under these conditions. To vary the level of IL-4 present, either IL-4 or anti-IL-4 was added to cultures. In the presence of IL-4 there was an increase in the proportion of clones that secreted IgE and a decrease in the proportion of clones that secreted IgM. The addition of IL-4 to cultures also increased the amount of IgE secreted by individual clones. Thus, these experiments definitively prove that IL-4 causes specific heavy chain class switching to IgE in Th2-stimulated B cell cultures. In contrast, IL-4 does not affect the proportion of clones secreting IgG1, suggesting that other consequences of Th cell-B cell interactions play a role in the generation of an IgG1 response.     

Antigen-specific immunoglobulins in patients with acute pulmonary, chronic pulmonary, or disseminated histoplasmosis

Patients infected with Histoplasma capsulatum exhibit protean clinical manifestations and similarly express variable humoral immune responses. Therefore, the specific goals of this study were to more clearly define host immune responses by determining the concentrations of total and H. capsulatum-specific immunoglobulins in sera from patients with acute or chronic pulmonary and disseminated histoplasmosis. H. capsulatum-specific (AS) IgG, IgA and IgM, and total IgE were determined by radioimmunoassays while total IgG, IgA, and IgM were quantitated by laser nephelometry. In general, total IgG and IgA were elevated, while IgM and IgE were either decreased or normal for the three clinical forms of histoplasmosis studies. Antigen-specific IgG and IgA were markedly elevated in all classes of disease, whereas AS-IgM was only slightly increased. Total and AS-IgG were elevated in the sera of chronic patients directly proportional to the number of demonstrable precipitin bands.     

格雷夫斯病患者的体液免疫功能分析

目的 检测格雷夫斯病(Graves,disease,GD)患者的临床免疫指标,进而分析机体的体液免疫功能和疾病的相关性.方法 收集51例GD患者(GD组)和20例正常对照者(NC组)的外周静脉血.检测促甲状腺激素(TSH)、血清总三碘甲腺原氨酸(TT3)、总甲状腺素(TT4)、游离甲状腺素(FTt)、游离三碘甲腺原氨酸(FT3)、免疫球蛋白IgA、IgG、IgM、补体C3、C4、自身抗体等指标并进行分析.结果 GD组IgA、IgG、IgM、C3、C4分别为(2.45±0.91)g/L、(14.14±3.49)g/L、(1.45±0.53)g/L、(1.33±0.36)g/L、(0.30±0.12)g/L,高于ND组(2.33±0.65)g/L、(13.44±1.69)g/L、(0.926±0.30)g/L、(1.12±0.17)g/L、(0.25±0.06)g/L.GD组抗核抗体阳性率为7.8%,IgA与IgG、IgA与IgM、IgG与IgM、C3与C4均呈正相关(r=0.381、0.391、0.316、0.713,均P<0.01).结论 GD患者的机体的体液免疫功能存在异常.联合检测甲状腺激素水平和免疫球蛋白组合有助于提高GD的诊断率.     

超鞭毛虫下呼吸道感染的发病机制及其免疫功能状态的研究

目的研究超鞭毛虫下呼吸道感染患者的免疫功能变化并初步探讨超鞭毛虫下呼吸道感染的发病机制。方法采用酶联免疫吸附法(ELISA法)检测超鞭毛虫下呼吸道感染患者和普通下呼吸道感染(非超鞭毛虫)患者血清中IgG、IgA、IgM、补体3(C3)、干扰素(IFN)-γ、白细胞介素(IL)-4,采用流式细胞仪检测两组患者T细胞亚群和NK细胞,两组间检测结果比较。结果与对照组相比,超鞭毛虫下呼吸道感染患者血清IgG、IgM、C3、CD4+、CD4+/CD8+、IFN-γ、IL-4水平明显改变(P<0.05)。结论超鞭毛虫下呼吸道感染体内存在一定的免疫功能紊乱,可能正是这种紊乱导致了超鞭毛虫能够感染人体下呼吸道。     

Immunoglobulin E level in acute Yersinia infection

IgG, IgE, IgA, IgM levels were measured in patients with yersiniosis (generalized or mixed variant). Acute period of the disease (week 1-2) was associated with elevated levels of IgE in 59.1% of the patients which returned to normal on week 4-6. Time course changes in IgA, IgG and IgM concentrations were related to the synthesis of specific antibodies. IgE level rise can be considered a defence mechanism contributing to elimination of yersinia antigens from the body.     

职业性接触灭蚁药物对人体免疫功能的影响

背景存在于生活、生产环境中的多种化学毒物在一定剂量下具有免疫毒性,灭蚁药物氯丹和含砷杀虫剂名列其中.职业性接触此类化学毒物是否会造成作业人员免疫系统损害?目的探讨职业性接触灭蚁药物对作业人员免疫水平的影响.设计病例-对照研究.单位原江苏省职业病防治院职业病科和毒化实验室.对象该研究于2002-01/2003-12在原江苏省职业病防治院职业病科和毒化实验室完成.接触组分设为白蚁防治组、砷药物生产组和氯丹生产组.3组研究对象分别选择来自本省某白蚁防治所的白蚁防治人员、某农药厂生产砷药物和生产氯丹的工人,共216名.选择身体健康的非职业性接触人群64人作为对照组.纳入标准①接触组工龄在2年以上者;②对照组为不接触有毒有害物质的健康自愿者,其他条件与接触组相似.排除标准①符合接触组纳入标准但工龄小于2年者;②不接触有毒有害物质但患有各种疾病者.方法采用美国Beckman公司生产的免疫化学系统ICS仪和PEG-紫外定量法,对作业人员进行了血清中IgG,IgA,IgM,C3,C4,CRP,CIC进行了检测.并对工龄、吸烟、饮酒和体内毒物的浓度对免疫水平的影响进行了分析.主要观察指标血清中IgG,IgA,Ig,MC3,C4,CRP,CIC水平.结果职业接触灭蚁药物使血清中IgG,IgA,IgM水平显著下降(t=2.16～2.35,P＜0.05),但不同工龄接触者的IgG,IgA,IgM水平差异无显著性意义;吸烟、饮酒能加重含砷和氯丹类灭蚁药物对人体免疫水平的影响,使IgG、IgA、IgM水平显著降低(t=1.76～5.68,P＜0.05～0.01);体内免疫球蛋白的水平与血清氯丹和尿砷含量呈负相关[r=(-0.5123)～(-0.2314),P＜0.05～0.001 ].结论职业性接触灭蚁药物能显著降低作业人员机体的免疫水平.     

胰岛素强化治疗对创伤患者免疫球蛋白、补体及单核细胞噬菌能力的影响

目的探讨胰岛素强化治疗对严重创伤患者血清免疫球蛋白与补体水平的变化以及外周血单核细胞大肠杆菌颗粒吞噬能力的影响。方法采用随机配对原则将外科重症加强治疗病房（ICU）收治的创伤严重度评分（ISS）〉20分的严重创伤患者分为胰岛素强化治疗组（目标血糖值4～6mmol／L）和常规治疗组（目标血糖值〈11．1mmol／L）。分别在入院时及入院后2、4、6和8d留取外周静脉血，检测血清免疫球蛋白（IgA、IgG、IgM）与补体（C3、C4）水平的动态变化，全血细胞与用异硫氰酸荧光素（FITC）标记的大肠杆菌共孵育后检测单核细胞噬菌能力。结果两组严重创伤患者血清IgA、IgG、IgM和C3、C4水平在入院时均较低，入院治疗后均开始升高，并在治疗6～8d达到或接近正常范围。胰岛素强化治疗后C3、C4水平明显低于常规治疗组（P均〈0．05），并呈现恢复延迟的特点，而血清IgA、IgG、IgM水平两组比较差异均无显著性（P均〉0．05）。强化治疗组患者治疗4d和6d单核细胞大肠杆菌吞噬能力比入院时显著增强，且2、4和6d的大肠杆菌FITC阳性率均显著高于常规治疗组（P均〈0．05）。结论胰岛素强化治疗能明显改善严重创伤后免疫功能，增强单核细胞噬菌能力，是提高患者机体抵抗力的有效方法之一。     

Murine Peyer''s patch T cell clones. Characterization of antigen- specific helper T cells for immunoglobulin A responses

We successfully cloned antigen-specific T cells from murine gut-associated lymphoreticular tissue, i.e., Peyer's patches, which are dependent upon T cell growth factor and independent of antigen for continuous growth. These clones exhibit helper activity for IgA responses to sheep erythrocytes (SRBC) and have been designated T helper (Th) A. Two broad categories of Th A clones have been maintained in continuous culture. The first group supports IgM and largely IgA anti-SRBC plaque-forming cell (PFC) responses in both normal and SRBC-primed splenic B cell cultures, whereas the second group supports low IgM, IgG1, and IgG2 and high IgA PFC responses. Subclones derived from single cells maintain the parent helper properties when propagated in culture for long periods (greater than 7 mo). Cloned Th A cells are antigen specific and do not support polyclonal or immune responses to other thymus dependent antigens in normal B cell cultures. Th A cells require full histocompatibility for helper functions because addition of cloned Th A cells to B cell cultures from other H-2 types does not result in IgA responses. Cloned Th A cells are Thy-1.2+ and Lyt-1+ and Lyt-2-, Ig-, and I-A-. Th A cells bear Fc receptors for IgA and do not possess receptors for IgM or IgG isotypes. Thus, T cells that primarily promote IgA isotype responses have been isolated in high frequency from murine PP, an anatomical site of major importance for induction and regulation of the IgA response.