Function of C3 in a humoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells,but only stimulates immunoglobulin synthesis by antigen-specific B cells

Previous studies have shown that an optimal humoral response to a primary protein antigen requires C3 and CR2 (CD21). Sera from non-immunized donors contain natural IgM and IgG antibodies to the primary antigen keyhole limpet haemocyanin (KLH), and these have been previously shown to form immune complexes (IC) that activate the classical pathway of C, fixing iC3b/C3dg onto the KLH antigen. Such KLH IC bind to CR2 on KLH-non-specific B lymphocytes, resulting in antigen processing and MHC class II-dependent presentation to KLH-specific helper T cells. KLH IC also induce B lymphocytes to express the CD80 co-stimulatory molecule via simultaneous CR2 ligation with C3 and FcγRII (CD32) stimulation by IgG natural antibody. The current study demonstrated that KLH IC ligation to either CR2 or FcγRII resulted in activation of a second co-stimulatory molecule, LFA-1 (CD11a, CD18). The possibility of polyclonal B cell stimulation by the presentation of KLH-iC3b/C3dg by antigen-non-specific B cells was excluded by demonstration that in vitro cultivation of peripheral blood mononuclear cells (PBMC) with KLH-iC3b/C3dg elicited only anti-KLH, and did not stimulate synthesis of antibodies to hepatitis C virus (HCV) or tetanus toxoid (TT). Of greatest significance, a specific anti-KLH response was only detectable in cultures stimulated with KLH-iC3b/C3dg and not in cultures stimulated with KLH alone or KLH-IgG. Thus, iC3b/C3dg that was bound to a primary protein antigen enhanced recognition and specific immunoglobulin synthesis by antigen-specific B cells, even though the antigen was taken up and processed via CR2 by both antigen-specific and non-specific B cells.     

前后路短节段固定融合治疗腰椎纵向劈裂骨折

目的：评价前后路短节段固定融合治疗腰椎纵向劈裂骨折的临床效果和安全性。方法：回顾性分析中南 大学湘雅二医院脊柱外科2005年3月至2013年5月采用的前后路短节段固定融合治疗的13例腰椎纵向劈裂骨折患者临床 资料,对所有患者的矫正情况进行随访,采用疼痛视觉模拟量表(visual analogue scale,VAS)评分、Oswestry功能障碍指 数(Oswestry disability index,ODI)对腰椎功能进行评估。结果：随访时间为24~60个月,平均42个月;手术时间185~300 min,平均248 min;术中失血量为600~1 500 mL,平均950 mL。所有患者术后均获得功能及自我形象的改善,在Cobb 角评估方面,术后2 d,12个月和末次随访测量Cobb角较手术前均有明显改善,差异均有统计学意义(P<0.05);VAS评 分和ODI评估术后2 d,12个月和末次随访测量结果较之术前均有改善, 差异均有统计学意义(P<0.05)。术后12个月与 末次随访的评估结果相比,差异无统计学意义(P>0.05)。根据美国脊髓损伤协会(ASIA)分级标准,在末次随访时,术 前8例D级患者中6例恢复至E级,其中3例未见进一步恢复;术前2例C级中1例恢复至D级,1例恢复至E级。所有病例 骨折均获愈合,愈合时间为3~6个月,平均4.5个月;术中3例有硬膜撕裂,术中给予修补;无神经血管损伤并发症病 例。结论：短节段伤椎置钉和旋棒复位是腰椎纵向劈裂不稳定骨折较好的手术选择。     

Efficacy of Amodiaquine/Artesunate Combination Therapy for Uncomplicated Malaria in Children Under Five Years in Ghana

Background

In 2005, following several years of declining efficacy of chloroquine, the Ministry of Health recommended the use of Amodiaquine/Artesunate combination therapy for the treatment of uncomplicated malaria. A system of continuous monitoring of therapeutic responses has been established in 10 district hospitals across the country. The data gathered will enable National Malaria Control Programme (NMCP) to respond to changes in the efficacy of the new treatment in a timely manner.

Objectives

To determine the 28 day therapeutic efficacy of Amodiaquine/Artesunate (AQ/AS) combination treatment in children with uncomplicated malaria in Ghana.

Methods

Children aged 6 – 59 months attending clinic with signs/symptoms of uncomplicated malaria at 9 district hospitals (3 in each of the 3 eco-epidemiological zones of the country) were eligible for enrolment. Enrolled children were followed up after treatment for a total of 28 days to record the clinical and parasitological resolution of their malaria episode as well as any adverse drug reactions.

Results

Treatment resulted in rapid and complete cure in almost all the children; 99.3% 14 days after treatment and 93.0%, 28 days after treatment. The majority of treatment failures on D28 were seen in the 3 sites located in the forest zones (Sunyani, Bekwai and Begoro). There was no case of Early Treatment Failure at both D14 and D28 assessments. Adverse events (AE''s) were minimal, less than 4%, with the most common complaint being vomiting.

Conclusion

AQ/AS combination for uncomplicated malaria is efficacious and safe in children less than 5 years.     

Regulation of CR3 (CD11b/CD18)-dependent natural killer (NK) cell cytotoxicity by tumour target cell MHC class I molecules

Phagocyte and NK cell CR3 functions as both an adhesion molecule and an iC3b receptor mediating cytotoxic responses to microorganisms. Cytotoxic activation of iC3b receptor function requires ligation of both a CD11b I-domain site for iC3b and a lectin site located in the C-terminus of CD11b. Because tumours lack the CR3-binding polysaccharides of bacteria and fungi, iC3b-opsonized tumours do not stimulate CR3-dependent cytotoxicity. Previous studies showed that NK cells could be induced to kill iC3b-opsonized tumours with small soluble β-glucans that bound with high affinity to CR3, bypassing the absence of similar polysaccharides on tumour membranes. Because CR3 signalling requires several tyrosine phosphorylation events, it appeared possible that CR3-dependent killing of autologous tumour cells might be suppressed by NK cell inhibitory receptors for MHC class I (KIR and CD94/NKG2) whose action involves recruitment of SHP-1 and SHP-2 tyrosine phosphatases. In the current study, Epstein–Barr virus (EBV)-transformed B cells were used as targets following opsonization with iC3b. Soluble β-glucan primed CR3 for killing of iC3b-coated B cells, but autologous class I-bearing targets were 84% more resistant than class I-deficient Daudi cells. Blockade of target cell class I with a MoAb specific for a domain recognized by both KIR and CD94/NKG2 resulted in comparable killing of class I⁺ B cells. By contrast, another MoAb to class II had no effect on cytotoxicity. These data suggest that NK cell recognition of class I suppresses CR3/tyrosine kinase-dependent cytotoxicity in the same way as it suppresses cytotoxicity mediated by other tyrosine kinase-linked receptors such as FcγRIIIA (CD16).