Immunity and protection, the unfolding of a tale

Immunological memory is at the core of protective mechanisms against microbial pathogens and possibly of defenses against tumors. Here, a new perspective is offered on the qualitative and quantitative aspects of the T cell response as it relates to protection. Two main points are proposed. First, the conditions of the initial immune response (priming) are critically important in the induction of T cell memory and protection. Second, at the present time, protection against microbial pathogens appears to correlate with the function of central memory T cells. A series of considerations and suggestions are being made for new ways to optimize the induction of protective T cell responses by vaccination both in the immunologically naive and experienced individual; emphasis is placed on: dose of antigen, the availability of T cell help, avoidance of overt inflammatory conditions and efforts to decelerate cellular senescence in responding T cells. Presented at the First Robert A Good Society Symposium, St. Perersburg, FL 2006.     

COX-2、Ki-67联合检测对良恶性前列腺病变鉴别诊断的价值分析

目的 探讨环氧合酶-2(COX-2)、细胞增殖核抗原Ki-67(Ki-67)联合检测对良恶性前列腺病变的鉴别诊断价值。方法 选取2017年1月至2019年6月本院收治的168例良恶性前列腺病变患者,将其中83例前列腺癌(PCa)患者设为PCa组,85例良性前列腺病变患者[良性前列腺增生（BPH）患者40例、前列腺上皮内瘤(PIN)患者45例]设为BPH+PIN组。检测两组前列腺病变组织的COX-2、Ki-67表达水平;分析前列腺组织中的COX-2、Ki-67表达水平与PCa临床病理特征的关系;采用受试者工作特征（ROC）曲线评价前列腺病变组织COX-2、Ki-67 mRNA表达水平对PCa的诊断和鉴别价值。结果 PCa组患者的前列腺组织中COX-2、Ki-67 mRNA及蛋白阳性表达率水平均高于BPH+PIN组（均P<0.001）;PCa组患者的前列腺组织中COX-2、Ki-67表达水平与临床分期、远处转移、淋巴结转移、浸润深度、分化程度有明显相关性（均P<0.05）,与年龄、组织类型无相关性（均P>0.05）;前列腺病变组织的COX-2、Ki-67 mRNA诊断PCa的曲线下面积（AUC）分别为0.885、0.868,灵敏度分别为83.13%、78.31%,特异度分别为91.76%、92.94%;两者联合鉴别PCa的灵敏度（95.18%）高于两项单独检测,而特异度（90.59%）低于两项单独检测。结论 前列腺病变组织中的COX-2联合Ki-67对PCa具有较高的诊断价值,可提高诊断灵敏度,且具有较高准确度,有助于临床鉴别良恶性前列腺病变。     

中性粒细胞与淋巴细胞比值对前列腺癌诊断的临床价值及与危险分级的关系

目的 分析中性粒细胞与淋巴细胞比值（NLR）单独或联合前列腺特异性抗原（PSA）和年龄预测前列腺癌（PCa）的临床价值及其与危险分级的关系。方法 收集2016年6月至2020年6月在新乡医学院第三附属医院和第一附属医院就诊的1 205例患者,根据诊断结果将患者分为对照组（1 060例）和PCa组（145例）。根据欧洲泌尿外科协会指南再将PCa患者分为低（48例）、中（62例）、高（35例）危组。比较患者的一般资料,采用单因素和多因素logistic回归分析影响PCa的危险因素,采用受试者工作特征（ROC）曲线评估NLR、PSA和年龄单独检测预测PCa的临床价值,并建立联合预测模型方程。比较不同PCa危险分级组间的NLR水平。结果 PCa组的年龄、PSA、空腹血糖（FBG）、NLR和单核细胞与淋巴细胞比值（MLR）高于对照组,淋巴细胞计数低于对照组,差异均有统计学意义（均P<0.05）。单因素logistic回归分析结果显示,年龄、PSA、淋巴细胞计数、血红蛋白、FBG和NLR与PCa均有相关性(均P<0.05)。多因素logistic回归分析结果显示,年龄、PSA和NLR为影响PCa的独立危险因素（均P<0.05）。PSA和NLR预测PCa的临床价值均高于年龄预测PCa的价值（Z=8.604、9.204,均P<0.001）。NLR、PSA和年龄联合检测建立的ROC曲线下面积为0.905,灵敏度和特异度为82.5%和80.7%。低危组、中危组和高危组的NLR水平分别为(2.05±0.26)、(2.36±0.34)和(2.75±0.61),三组差异有统计学意义（F=32.021,P<0.001）,且高危组的NLR水平均高于中危组和低危组（q=11.132、6.494,均P<0.001）,中危组的NLR水平高于低危组（q=5.709,P<0.001）。结论 NLR为PCa的独立危险因素,与患者的危险度分级有关,与PSA和年龄联合检测可有效预测PCa。     

Association between KIR genes and dust mite sensitization in a Brazilian population

Background

Killer cell immunoglobulin-like receptors (KIRs), found on the surface of natural killer (NK) cells, play a key role in controlling the innate response. Such response depends on a series of cellular interactions between these receptors and HLA activating/inhibiting ligands. Atopic diseases have been associated with genes that regulate cytokine production and HLA genes, which may either protect or predispose to hypersensitivity.

Immunogenetic factors in early immune control of human immunodeficiency virus type 1 (HIV-1) infection: Evaluation of HLA class I amino acid variants in two African populations

Immune control of HIV-1 infection depends heavily on cytotoxic T-lymphocyte responses restricted by diverse HLA class I molecules. Recent work has uncovered specific amino acid residues (AARs) that seem to dictate the extent of immune control in African Americans, which prompted us to test these emerging hypotheses in seroconverters (SCs) from southern and eastern Africa. Based on data from 196 Zambians and 76 Rwandans with fully resolved HLA alleles and pre-therapy HIV-1 viral loads (VL) in the first 3- to 36-month of infection (>2300 person-visits), four AARs of primary interest (positions 63, 97, 116 and 245 in the mature HLA-B protein) were found to explain 8.1% and 15.8% of variance in set-point VL for these cohorts (P?=?.024 and 7.5?×?10^?6, respectively). Two AARs not reported previously (167S in HLA-B and 116F in HLA-C) also showed relatively consistent associations with VL (adjusted P?=?.009–.069), while many population-specific associations were also noted (false discovery rate <0.05). Extensive and often strong linkage disequilibrium among neighboring AAR variants called for more extensive analyses of AAR haplotypes in diverse cohorts before the structural basis of antigen presentation can be fully comprehended.     

PRAME peptide‐specific CD8+ T cells represent the predominant response against leukemia‐associated antigens in healthy individuals

Antigen‐specific T cells isolated from healthy individuals (HIs) have shown great therapeutic potential upon adoptive transfer for the treatment of viremia in immunosuppressed patients. The lack of comprehensive data on the prevalence and characteristics of leukemia‐associated antigen (LAA)‐specific T cells in HIs still limits such an approach for tumor therapy. Therefore, we have investigated T‐cell responses against prominent candidates comprising Wilms’ tumor protein 1 (WT1), preferentially expressed antigen in melanoma (PRAME), Survivin, NY‐ESO, and p53 by screening PBMCs from HIs using intracellular IFN‐γ staining following provocation with LAA peptide mixes. Here, we found predominantly poly‐functional effector/effector memory CCR7^?/CD45RA^+/?/CD8⁺ LAA peptide‐specific T cells with varying CD95 expression in 34 of 100 tested HIs, whereas CD4⁺ T cells responses were restricted to 5. Most frequent LAA peptide‐specific T cell responses were directed against WT1 and PRAME peptides with a prevalence of 20 and 17%, respectively, showing the highest magnitude (0.16% ± 0.22% (mean ± SD)) for PRAME peptides. Cytotoxicity of PRAME peptide‐specific T cells was demonstrated by specific killing of PRAME peptide‐pulsed T2 cells. Furthermore, the proliferative capacity of PRAME peptide‐specific T cells was confined to HIs responsive toward PRAME peptide challenge corroborating the accuracy of the screening results. In conclusion, we identified PRAME as a promising target antigen for adoptive leukemia therapy.     

催乳素对子宫腺肌症发病影响的实验研究

目的探讨催乳素(PRL)在子宫腺肌症(adenomyosis,AM)发病机制中的临床意义。方法采用时间分辨荧光免疫法检测63例AM患者手术前、后血清PRL水平和血清CA125水平。同时,随机抽取63例同期手术治疗的子宫肌瘤患者作为对照组。结果AM组患者术前血清PRL和CA125均值分别为(53.17±15.62)ng/ml和(49.67±12.84)U/L,明显高于子宫肌瘤组的(14.23±3.76)ng/ml和(10.34±2.98)U/L,各组均数间差异有统计学意义(P<0.01)。术后2个月,AM组患者血清PRL和CA125均值分别降为(14.78±4.77)ng/ml和(9.13±1.91)U/L,较术前明显下降,各组均数手术前后其差异具有极显著统计学意义(P<0.01)。对照组患者其手术前、后PRL和CA125均值变化较小,各组均数差异无统计学意义(P>0.05)。结论与CA125相比,PRL在AM发病中起着更为重要的作用,PRL和CA125的联合检测有助于对AM的诊断和治疗的监测。     

CD31和Ki-67在大肠癌组织中的表达和相关性研究

目的 :探讨 CD31和 Ki- 6 7在大肠癌组织中的表达的意义和二者之间的相关性。方法 :采用免疫组化染色检测 CD31和 Ki- 6 7在 4 8例大肠癌标本中的表达。结果 :1CD31随着大肠癌分化程度的降低其表达率呈上升趋势。 2CD31表达与大肠癌的分化程度浆膜浸润和淋巴结转移有关。 3Ki- 6 7的表达与大肠癌的分化程度有关。 4 CD31和 Ki-6 7表达呈显著正相关。结论 :检测 CD31和 Ki- 6 7在大肠癌中的表达有助于了解病变的发展阶段和预后评估 ;CD31和Ki- 6 7表达呈正相关 ,CD31过度表达区域 ,Ki- 6 7表达率也增高 ,推测两者在大肠癌的增殖调控以及发生、发展中有协同作用。     

前列腺弱回声灶和PSAD对前列腺癌的诊断价值

目的:探讨前列腺内局限性弱回声灶与PSAD的关系,以提高对前列腺癌的早期检出率。方法:采用直肠超声法。结果:检出前列腺弱回声灶65例,范围0.5～2.0cm~2,84.61％位于移行区。病检证实前列腺癌(PCa)35例(53.84％),前列腺上皮内瘤(PIN)13例(20％),结节增生17例(26.15％)。以PSA10ng/ml和PSAD0.1为界值,对PCa和PIN的敏感性是52％和85％,特异性90％和56％,阳性预测值90％和71％。结论:前列腺弱回声灶和PSAD较单一指标能提高对前列腺癌的检出率。