Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.     

Flow cytometry analysis of platelet antibodies

We have devised assays to detect both circulating alloantibodies to platelets (indirect assay) and platelet-association IgG and IgM (direct assay) using a flow cytometric technique. A variety of patients with immune thrombocytopenia were studied. Employment of a confocal lens in the flow cytometer increased the discrimination power of the instrument. Patients with autoimmune thrombocytopenia (idiopathic thrombocytic purpura [ITP], systemic lupus erythematosus (SLE), lymphoma, leukemia, and drug-induced thrombocytopenia showed a significant increase in platelet-associated antibody. Circulating antibodies to platelets (alloantibodies) were demonstrated in cases of platelet refractoriness and neonatal isoimmune purpura. Day-today precision of the assays ranged from 3% to 6% (coefficient of variation). No interference was shown in the presence of hemoglobin (5 g/L), triglycerides (10 g/L), or polyclonal and monoclonal immunoglobulinemia (50 g/L: IgG, IgA, IgM). The sensitivity of the direct assay was 500 attograms of IgG or IgM platelet.     

The Last 5 Years of Basic Science Investigation in Transplant Immunology

Many new insights have been gained over the past 5 years into the mechanisms that regulate immune reactivity to cell and organ transplants. This new knowledge is being applied to the development of innovative experimental strategies that may soon be evaluated in the clinic.     

维生素D衍生物联合供者骨髓细胞输注诱导异基因大鼠心脏移植免疫耐受

目的 探讨同种异基因心脏移植后免疫耐受的诱导。方法 建立大鼠颈部异位心脏移植模型，按分组分别给予门静脉输注供者骨髓细胞(DBMC)(B组)、骨化三醇灌胃(C组)、输注DBMC及骨化三醇灌胃(D组)以及环孢素A(CsA)灌胃(E组)。观察移植心脏的存活时间及心肌组织病理改变，测定心肌组织中肿瘤坏死因子及细胞间粘附分子-1 mRNA的表达以及血清钙、磷浓度，进行受者与供者及无关第三品系大鼠脾细胞混合淋巴细胞培养(MLR)。结果 D组移植心脏的存活时间较其它各组显著延长(P＜0．05)；术后7d，C组、D组、E组受者脾细胞均能显著抑制供者及第三方无关供者脾细胞作为刺激细胞引起的MLR；D组手术前后血磷、血钙浓度的差异无显著性(P＞0．05)；各组急性排斥反应的程度，D组最轻；D组肿瘤坏死因子及细胞间粘附分子-1 mRNA的表达受到显著抑制，与对照组(A组)、B、C组比较，差异有显著性(P＜0．05)。结论 骨化三醇灌胃联合DBMC输注可显著延长移植心脏的存活时间，二者具有协同作用。     

白细胞介素-10诱导的大鼠树突状细胞体外免疫功能的研究

目的　研究白细胞介素 10 (IL 10 )诱导的大鼠未成熟树突状细胞 (imDCs)体外诱导免疫耐受的可行性。方法　在经典诱导方案的基础上 ,应用IL 10 ( 10 μg/L)抑制大鼠骨髓来源DCs的成熟 (IL 10组 ,10例 ) ,并设对照组 (IL 4组 ,10例 )。培养期间观察DCs形态 ,检测DCs表型、摄取抗原能力、体外免疫功能及培养上清细胞因子水平。结果　与IL 4组比较 ,IL 10组DCs细胞表面CD80 、CD86及OX6低度表达 ( 2 5 .3 %、42 .4%、3 2 .3 % ) ,吞噬能力较强 ( 81.9) ,刺激同种异体淋巴细胞增殖能力下降 ,该淋巴细胞具有抗原特异性低反应性 ;培养上清中IL 12水平 ( 4 0 6.5pg/L)及初次MLR培养上清IL 2水平 ( 2 45 .4ng/L)均较低 ,差异有非常显著性 (P <0 .0 1)。 结论　IL 10作用的大鼠imDCs具有诱导免疫耐受的应用价值。     

马桑内酯所致癫痫发作大鼠红细胞免疫粘附功能的研究

作者用红细胞Ｃ＿３ｂ受体花环试验和红细胞免疫复合物花环试验对马桑内酯所致癫痫发作大鼠红细胞免疫粘附功能的变化进行了观察，结果表明，癫痫组动物红细胞Ｃ＿３ｂ受体花环率明显低于对照组，而红细胞免疫复合物花环率相差不显著．提示癫痫发作可导致大鼠红细胞免疫粘附功能降低，因此在癫痫治疗中注意调整和增强患者的红细胞免疫功能具有重要意义。     

白细胞介素—2新的功能位点及其中枢镇痛作用

白细胞介素－２（ＩＬ－２）不仅是重要的免疫调节因子，而且还具有重要的中枢调节作用。本实验以钾离子透入引起大鼠甩尾反应为指标，发现侧脑室注射ＩＬ—２能显著提高动物痛阈，并能被纳洛酮所阻断，表示ＩＬ－２的中枢镇痛作用可能与阿片受体有关。利用基因定位突变技术获得的无免疫活性ＩＬ－２实查体仍具有中枢镇痛作用，表明ＩＬ—２分子上发挥镇痛和免疫调节作用的功能位点是相互独立的。纳洛酮能够阻断ＩＬ—２的中枢镇痛作用，而不能影响ＩＬ—２增殖ＣＴＬＬ－２细胞的作用，提示ＩＬ－２发挥镇痛和免疫调节作用可能通过不同的受体途径。ＩＬ－２分子中第４５位Ｔｙｒ残基突变为Ｖａｌ后，虽仍保留了免疫活性，但丧失了镇痛功能，表示４５位Ｔｙｒ残基是ＩＬ—２发挥中枢镇痛功能的关键残基之一。我们推测ＩＬ—２的镇痛功能位点可能在ＩＬ—２分子中第４５位Ｔｙｒ残基附近区域。     

Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro

We have earlier found increased percentages of T helper cells (CD4-positive lymphocytes) in the blood circulation after propofol infusion anaesthesia. Cytokines interferon-γ (IFNγ) and interleukin-4 (IL-4) are important in the differentiation of T helper cells into subtypes T helper type-1 (Th1) and type-2 (Th2). To study the effects of propofol emulsion, its solvent Intralipid^® and thiopentone on Th1/Th2 balance, measurements of IFNγ and IL-4 production by mononuclear leucocytes were carried out in vitro . As IL-2 has a central role in immune responses to surgery, its production was also measured. Concanavalin A-stimulated mononuclear cells were cultured in the presence of propofol emulsion at 3.5 or 10 μg.ml⁻¹, Intralipid^® 35 or 100 μg.ml⁻¹, or thiopentone 3 μg.ml⁻¹. Cytokine production was measured from the conditioned media of mononuclear cell cultures. Decreased IFNγ (p <0.001) and IL-4 concentrations (p < 0.01) were found in the presence of thiopentone, but IL-2 production was unaffected. By contrast, propofol emulsion or Intralipid^® had no effects on IFNγ, IL-2 or IL-4 concentrations. Propofol 10 μ.ml⁻¹ increased the IFNγ/IL-4 ratio from the control value median 243 (162–562) (25th–75th percentile) to 363 (195–1028) (p < 0.01), but thiopentone decreased it to 145 (60–214) (p < 0.01). These findings show that propofol and thiopentone have different effects in vitro on Th1/Th2 balance and suggest that they have different modulating effects on the immune response.