蒲黄醇提取物对C57BL／6荷瘤小鼠免疫功能的影响

[目的]研究蒲黄醇提物对C57BIM6荷瘤小鼠免疫功能影响。[方法]通过建立Lewis肺癌小鼠移植瘤动物模型,以抑瘤率为指标考察蒲黄醇提物的体内抗肿瘤活性,分别测定其抑瘤率、胸腺指数和脾脏指数;四氮唑盐（MTY）法对荷瘤小鼠脾淋巴细胞增殖活性进行测定;ELISA法测定荷瘤小鼠血清中白细胞介素一2（IL-2）、肿瘤坏死因子-a（TNF-a水平。[结果]蒲黄醇提取物100mg／kg·d组对肿瘤生长有明显的抑制作用（P〈0．01）,其抑瘤率为48．3％,蒲黄醇提物三个剂量组均能提高荷瘤小鼠的胸腺指数和脾脏指数。同时100和200mg／kg·d组能显著提高荷瘤小鼠脾淋巴细胞的增殖能力和荷瘤小鼠血清中IL-2、TNF—ol的水平。[结论]蒲黄醇提物具有提高荷瘤小鼠体液免疫和细胞免疫的作用。     

CTLA-4 control over Foxp3+ regulatory T cell function

Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.     

Selective stimulation of T cell subsets with antibody-cytokine immune complexes

Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2-dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.     

中药复方抗鸡新城疫作用及其对雏鸡免疫内分泌调节的影响

为筛选抗鸡新城疫中药复方并观察中药复方对雏鸡免疫内分泌调节的影响,将152羽30日龄健康免疫雏鸡随机分为5组:3个中药复方组(方1、方2、方3)、病毒对照组和空白对照组.人工感染鸡新城疫病毒(NDV)后,观察鸡群的发病情况,并于试验各期随机心脏采血,测定外周血淋巴细胞转化和血清抗体、白介素-2(IL-2)、白介素-6(IL-6)、干扰素-γ(IFN-γ)、甲状腺素(T4)及胰高血糖素(Glu)的水平.结果表明:中药复方能延缓鸡新城疫的发病时间,减轻病理损伤,促进病鸡康复,有效降低鸡的死亡率,尤以方3效果最好.方1和方3能快速提高抗体水平;方1能提升血清IFN-γ和T4的水平,方2能提高血清IL-2的含量,方3则可提高血清IL-2、IL-6和T4的水平,3个中药复方都可降低鸡死亡高峰期血清IL-6和Glu的水平.研究表明,中药复方能快速刺激免疫鸡体内体液免疫应答,并通过免疫内分泌整体调节途径以抵抗NDV感染,不同组方原则的复方调节途径可能也不一致,但方3的效果整体上优于方1和方2.     

Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones

The production and action of immunoregulatory cytokines, including interleukin-1 (IL-1), are inhibited by glucocorticoid hormones in vivo and in vitro. Conversely, glucocorticoid blood levels were increased by factors released by human leukocytes exposed to Newcastle disease virus preparations. This activity was neutralized by an antibody to IL-1. Therefore the capacity of IL-1 to stimulate the pituitary-adrenal axis was tested. Administration of subpyrogenic doses of homogeneous human monocyte-derived IL-1 or the pI 7 form of human recombinant IL-1 to mice and rats increased blood levels of adrenocorticotropic hormone (ACTH) and glucocorticoids. Another monokine, tumor necrosis factor, and the lymphokines IL-2 and gamma-interferon had no such effects when administered in doses equivalent to or higher than those of IL-1. The stimulatory effect of IL-1 on the pituitary-adrenal axis seemed not to be mediated by the secondary release of products from mature T lymphocytes since IL-1 was endocrinologically active when injected into athymic nude mice. These results strongly support the existence of an immunoregulatory feedback circuit in which IL-1 acts as an afferent and glucocorticoid as an efferent hormonal signal.     

T-cell tumor elimination as a result of T-cell receptor-mediated activation

It has recently been shown that activation of murine T-cell hybridomas with antigen inhibits their growth in vitro. The "suicide" of these neoplastic T cells upon stimulation with antigen suggested the possibility that activation via the antigen-specific receptor could also inhibit the growth of neoplastic T cells in vivo. To test this, mice were subcutaneously inoculated with antigen-specific T-cell hybridomas and then treated intraperitoneally with antigen. Administration of the appropriate antigen immediately after inoculation with the T-cell hybridoma abrogated tumor formation; antigen administered after tumors had become established decreased the tumor burden and, in a substantial fraction of animals, led to long-term survival. The efficacy of antigen therapy was due to both a direct inhibitory effect on tumor growth and the induction of host immunity. These studies demonstrate the utility of cellular activation as a means of inhibiting neoplastic T-cell growth in vivo and provide a rationale for studying the use of less selective reagents that can mimic the activating properties of antigen, such as monoclonal antibodies, in the treatment of T-cell neoplasms of unknown antigen specificity.     

Studies on Immunoregulation of Cytokine of Chickens after Inoculation with Marek''''s Disease Vaccines

The spleenic and thymus T lymphocyte proliferaitivc reactions (TLPR) were enhanced, the intcrlcukin 2(IL-2) inductive activity was raised, and the IL-2 receptor (IL-2R) inductive expression was increased significantly in chickens after inoculation with trivalcnt Marck's disease vaccine in comparison with control chickens and those after vaccination with herpcsvirus of turkey (HVT) vaccine. In chickens after inoculation with HVT vaccine, in contrast with control chickens, the splcenic TLPR was strengthened and IL-2R inductive expression was hoisted significantly, the thymus TLPR, splccnic and thymus T lymphocyte IL-2 inductive activity, the thymus T lymphocyte IL-2R inductive expression were not significantly increased.     

亚麻木脂素对小鼠淋巴细胞、巨噬细胞、IL-2免疫功能的影响

文章为研究亚麻木脂素对小鼠免疫功能的影响,选用雌雄各半,体重18～22 g的ICR小鼠120只,随机分为对照组和试验低、中、高3个剂量组,小鼠分别经口给予0.6,1.2,3.6 g.kg-1.d-1的木脂素(SDG),持续30 d后测其各项免疫指标,结果表明,3个剂量组的小鼠T淋巴细胞中IL-2细胞活性分别提高57.8%、64.2%、67.4%;巨噬细胞吞噬水平分别提高55.4%、57.0%、59.7%,与对照组比较差异显著(P<0.05,P<0.01);中、高剂量组可使小鼠脾淋巴细胞转化率分别提高58.9%、62.3%;溶血空斑数分别增加51.8%、53.1%;NK细胞活性分别提高58.9%、62.7%,与对照组比较差异显著(P<0.05,P<0.01)。结果表明木脂素具有增强小鼠免疫功能的作用。     

鸡白细胞介素-2的研究进展及应用前景

鸡白细胞介素-2(IL-2)是由激活的T细胞分泌产生的糖蛋白,是鸡体内一类重要的细胞因子,在机体的免疫应答中起重要作用。近年来,随着鸡的IL-2基因克隆成功,使鸡的IL-2研究及应用得到了一定的发展,同时作为免疫增强剂和构建新型基因工程疫苗呈现出一定的应用前景。     

林蛙油活性肽对小鼠免疫功能的影响

以林蛙油蛋白双酶水解超滤后获得的2种不同分子质量区间的活性肽BPOR1及BPOR2为试验原料,体外通过脾淋巴细胞增殖试验,分别加入不同剂量的BPOR1、BPOR2和Con A诱导,观察淋巴细胞的增殖情况,体内通过灌胃不同剂量BPOR1及BPOR2(100、300、600 mg·kg-1·d-1)30 d,以脾脏指数和胸腺指数的变化来观察2种活性肽对小鼠免疫器官的影响,利用流式细胞仪检测小鼠T淋巴细胞亚群的变化情况。结果表明:BPOR1可明显地促进小鼠脾淋巴细胞增殖,且具有对Con A诱导的脾淋巴细胞增殖的协同刺激作用。2种混合肽对小鼠脾脏指数和胸腺指数比均有影响,并且都能影响小鼠CD3+、CD4+、CD8+T淋巴细胞亚群的分布。可见,林蛙油活性肽能增加小鼠的免疫能力,且BPOR1的作用效果比BPOR2明显。     

Vital involvement of a natural killer cell activation receptor in resistance to viral infection

Natural killer (NK) cells are lymphocytes that can be distinguished from T and B cells through their involvement in innate immunity and their lack of rearranged antigen receptors. Although NK cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based activation motif (ITAM)-containing transmembrane molecule for expression and signal transduction. Thus, NK cells use receptors functionally resembling ITAM-coupled T and B cell antigen receptors to provide vital innate host defense.     

意大利蜂工蜂幼虫和蛹的药理作用初探

从抗肿瘤、抗衰老、调节机体免疫功能三方面对工蜂幼虫、蛹的药理作用进行了研究,结果表 明,工蜂幼虫、蛹对小鼠Ｓ１８０肿瘤生长有明显的抑制作用,其抑瘤率分别达６０．９２％和６４．３７％,荷瘤小鼠的生命延长率分别达８０． ６５％和８１． ７４％;工蜂幼虫、蛹能提高大鼠脑、肝脏和血液中ＳＯＤ的活性,降低ＭＤＡ的含量,提高小鼠脑组织中ＲＮＡ和蛋白质的含量;工蜂幼虫、蛹能提高小鼠Ｔ淋巴细胞转化功能、碳廓清指数和胸腺指数,具有提高机体的细胞免疫和非特异性免疫功能的作用,工蜂幼虫、蛹的药理作用与蜂王幼虫相比,差异不显著。     

猪链球菌2型灭活疫苗对小鼠的免疫效果评价

在前期筛选出2株毒力强、抗原性好、遗传稳定的猪链球菌2型(SS2)疫苗菌株(HF2、HF3株)并分别制成灭活疫苗(采用ISA 201 VG矿物油佐剂)的基础上,进一步与SS2商品化灭活疫苗(HA9801株,铝胶佐剂)同步免疫小鼠,利用间接ELISA、流式细胞术、免疫攻毒试验、细菌定植试验和病理组织学观察等方法测定小鼠血清中IgG抗体效价,细胞因子含量(IL-4、IL-10、IFN-γ、TNF-β、MCP-1),外周血中CD4⁺/CD3⁺、CD8⁺/CD3⁺ T细胞亚群含量,攻毒保护率,组织荷菌数和病理组织变化等指标。结果显示,二免7 d后,HF2、HF3灭活疫苗组和HA9801商品化灭活疫苗组的血清IgG抗体效价分别为1:25 600、1:12 800、1:25 600;HF2灭活疫苗组的IL-4、IL-10含量显著高于HF3灭活疫苗组和HA9801商品化灭活疫苗组,IFN-γ、TNF-β含量显著高于HF3灭活疫苗组,但MCP-1含量显著低于HF3灭活疫苗组;HF2和HF3灭活疫苗组的CD4⁺/CD3⁺ T细胞比率均显著低于HA9801商品化灭活疫苗组,但CD8⁺/CD3⁺ T细胞比率差异不显著;HF2、HF3灭活疫苗和HA9801商品化灭活疫苗对小鼠的攻毒保护率均为100%;HF2灭活疫苗组小鼠的肺、脾脏组织荷菌数显著低于HF3灭活疫苗组;HF2灭活疫苗组小鼠的肺、肾、脾脏病理变化较HF3灭活疫苗组和HA9801商品化灭活疫苗组轻微。综合结果表明,由SS2(HF2株)制备的ISA 201 VG佐剂灭活疫苗免疫小鼠后不仅可产生较强的免疫应答,还可完全抵抗强毒株的攻击。     

Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4

The generation of antigen-specific antitumor immunity is the ultimate goal in cancer immunotherapy. When cells from a spontaneously arising murine renal cell tumor were engineered to secrete large doses of interleukin-4 (IL-4) locally, they were rejected in a predominantly T cell-independent manner. However, animals that rejected the IL-4-transfected tumors developed T cell-dependent systemic immunity to the parental tumor. This systemic immunity was tumor-specific and primarily mediated by CD8+ T cells. Established parental tumors could be cured by the systemic immune response generated by injection of the genetically engineered tumors. These results provide a rationale for the use of lymphokine gene-transfected tumor cells as a modality for cancer therapy.     

鹅绒委陵菜多糖对荷瘤小鼠细胞因子的影响

[目的]研究鹅绒委陵菜多糖(PAP)对荷瘤小鼠外周血细胞因子白介素-2(TL-2)和肿瘤坏死因子-α(TNF-α)的影响。[方法]建立肉瘤S180小鼠动物模型,灌胃给予50、100和200 mg/kg剂量的PAP,以抑瘤率为指标,考察鹅绒委陵菜多糖的体内抗肿瘤活性,测定其抑瘤率;ELISA法测定荷瘤小鼠血清中白细胞介素-2(IL-2)和肿瘤坏死因子-α(TN-α)的水平。[结果]低、中、高3个剂量的PAP对S180荷瘤小鼠的抑瘤率分别为46.41%、52.29%和59.48%;其中CY和低剂量的多糖组合抑瘤率与中、高剂量的多糖抑瘤率相当,并明显高于单用环磷酰胺组的抑瘤率;低、中、高3个剂量的PAP能明显提高荷瘤小鼠血清中IL-2、TNF-α的水平。[结论]鹅绒委陵菜多糖具有提高荷瘤小鼠细胞免疫的作用。     

犬白细胞介素-7基因对犬细小病毒DNA疫苗的免疫增强作用

【目的】白介素-7是动物体一种重要的多功能细胞因子,在促进B细胞、T细胞的形成和发育,在协同其它细胞因子提高机体免疫能力等方面发挥重要作用。本试验利用犬细小病毒VP2 DNA疫苗,在小鼠体内分析了犬白介素-7（cIL-7）基因的免疫增强作用。【方法】采用RT-PCR方法从犬脾淋巴细胞中扩增cIL-7基因,然后将cIL-7基因插入到真核表达载体pcDNA3.1A中,分别构建成与Myc/His标签融合和非融合的cIL-7真核分泌型表达载体pcDNA-cIL7/MH和pcDNA-cIL7。由磷酸钙介导将pcDNA-cIL7/MH质粒转染HEK 293T细胞使其进行瞬时表达,以Western-blot检测构建的表达载体能否介导cIL-7基因在真核细胞中进行分泌表达。用已构建的VP2表达载体pcDNA-CD5-VP2与pcDNA-cIL7载体共免疫小鼠,并设pcDNA-CD5-VP2单免疫小鼠和pcDNA-cIL7单免疫小鼠作为对照。免疫后通过ELISA方法检测抗体水平,并通过淋巴细胞增殖实验和ELISA方法分别检测免疫后35 d小鼠脾脏淋巴细胞刺激指数和γ-干扰素的表达水平。【结果】本试验扩增的cIL-7基因序列与GenBank中犬的序列完全一致。构建的表达载体能够介导cIL-7基因在HEK293T细胞中进行分泌表达。动物免疫试验结果显示,cIL-7与VP2共免疫组小鼠血清的抗体滴度和中和抗体效价分别极显著和显著高于VP2单免疫组（P＜0.01和P＜0.05）;共免疫组小鼠淋巴细胞刺激指数和γ-干扰素表达水平也显著高于VP2单免疫组（P＜0.05）。【结论】cIL-7基因可增强小鼠对VP2 DNA疫苗的免疫应答反应。     

马齿苋多糖对雏鸡胸腺免疫功能的影响及其机制

为了观察马齿苋多糖(Portulace oleracea polysaccharide,POP)对雏鸡胸腺免疫功能的影响,并探讨其可能的作用机制,试验通过对雏鸡灌注不同剂量的POP,测定雏鸡胸腺指数,应用MMT(四甲基偶氮唑盐比色法)方法测定雏鸡胸腺淋巴细胞转化率,利用流式细胞器测定雏鸡胸腺淋巴细胞周期与胸腺T淋巴细胞亚群的变化.结果表明,POP能显著增加雏鸡胸腺淋巴细胞转化率和胸腺指数(P＜0.05),淋巴细胞增殖指数显著提高(P＜0.05),CD4+T淋巴细胞含量显著增加(P＜0.05),CD8+T淋巴细胞数量变化不明显,CD4+/CD8+T淋巴细胞比值显著升高(P＜0.05).POP可通过调节雏鸡胸腺内细胞水平的变化,增强雏鸡细胞免疫功能,促进免疫系统发育.