Role of CD4+ T Cells in the Control of Viral Infections: Recent Advances and Open Questions

CD4+ T cells orchestrate adaptive immune responses through their capacity to recruit and provide help to multiple immune effectors, in addition to exerting direct effector functions. CD4+ T cells are increasingly recognized as playing an essential role in the control of chronic viral infections. In this review, we present recent advances in understanding the nature of CD4+ T cell help provided to antiviral effectors. Drawing from our studies of natural human immunodeficiency virus (HIV) control, we then focus on the role of high-affinity T cell receptor (TCR) clonotypes in mediating antiviral CD4+ T cell responses. Last, we discuss the role of TCR affinity in determining CD4+ T cell differentiation, reviewing the at times divergent studies associating TCR signal strength to the choice of a T helper 1 (Th1) or a T follicular helper (Tfh) cell fate.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

Different durations of whole raw soybean supplementation during the prepartum period: Measures of cellular immune function in transition cows

The objective of this study was to evaluate different durations of whole raw soybean (WS) supplementation (diet rich in n-6 fatty acid) during the prepartum period on cellular immune function of dairy cows in the transition period and early lactation. Thirty-one Holstein cows were used in a completely randomized design and assigned to 4 experimental groups (G) [G90, G60, G30, and G0 (control)] supplemented with a diet containing 12% of WS from 90, 60, 30 and 0 d relative to the calving date, respectively. Cows were dried off 60 d before the expected calving date. After parturition, all cows were fed a diet containing 12% of WS until 84 DIM. Blood samples were collected before the morning feeding (d ?56 ± 2, ?28 ± 2, ?14 ± 2, ?7 ± 2, at the day of partum, 7 ± 2, 14 ± 2, 28 ± 2, and 56 ± 2 relative to parturition). Cell phenotyping and phagocytosis assays were carried out using monoclonal antibodies and flow cytometry technique. Duration of WS supplementation linearly increased the percentage of blood CD3⁺ cells, as well as increased the percentage of blood CD8⁺ cells in the postpartum period, notably in G30, whereas the lowest values were observed in G0. Further, the duration of WS supplementation linearly increased the reactive oxygen species median fluorescence intensity of CH138⁺ cells after phagocytizing Staphylococcus aureus in the postpartum period. Longer periods of WS supplementation linearly increased phagocytosis median fluorescence intensity of CH138⁺ cells in the prepartum period of cows. Duration of WS supplementation linearly increased the percentage of blood CD14⁺ cells producing reactive oxygen species when stimulated either by Staph. aureus or Escherichia coli in the postpartum period. In conclusion, longer periods of WS supplementation during late lactation and the dry period (beginning on d 90 of the expected calving date) alter the leukocyte population and improve neutrophil immune response in the postpartum period with no detrimental effects on cow performance.     

基于过程免疫力的动态电压恢复器优化配置

优质电力园区以最低成本满足用户对电能质量的特殊需求,成为解决电压暂降问题的新途径,已在国内外开展了广泛的试点应用。针对中国优质电力园区规划缺少经济高效的优化配置方法的实际情况,提出了一种基于过程免疫力的动态电压恢复器优化配置方法。基于工业过程电压暂降免疫力,以满足用户用电需求为目标,以治理设备购置费用最低为约束,采用遗传算法对园区供电质量分级制定动态电压恢复器的优化配置方案,实现工业园区电压暂降治理的经济性。对大型精密温控系统的电压暂降治理装置的优化配置方法进行仿真计算,验证了所提方法的有效性与经济性。     

基于自适应免疫遗传算法的IPPS问题研究

针对工艺规划与调度集成(Integration of Process Planning and Scheduling,IPPS)的多目标优化问题,将遗传算法基本理论与免疫应答机理相结合,并引入IPPS问题研究中,构造了融遗传算法和免疫机理为一体的自适应免疫遗传算法(Self-adaptive Immune Genetic Algorithm,SIGA)。该算法以遗传算法为主体并加入免疫算子,通过免疫系统的自适应、免疫识别、学习、记忆、激增和抑制等复杂的信息处理机理,有效地解决了规模大、约束多、目标函数非单一的IPPS问题。最后以实例进行仿真优化,验证了模型算法的正确性和有效性。     

Colostrum source and passive immunity transfer in dairy bull calves

Colostrum is essential for good neonate health; however, it is not known whether different calves absorb the nutrients from colostrum equally well. In this study, the absorption of protein, IgG, and γ-glutamyl transferase was compared in newborn dairy bull calves for 1 wk after feeding colostrum from different sources. Thirty-five Holstein-Friesian bull calves were randomly allocated into 3 groups and fed colostrum within 4 h after birth. Group A calves (n = 12) were bottle fed colostrum from their own dam for 3 d. Colostrum from these group A cows was also used as foster cow colostrum for the group B calves (n = 12), such that each group A and B calf pair received identical colostrum from each milking of the respective group A dam (10% of birth weight per day). The group C calves (n = 11) were fed 1 bottle (2 L) of pooled colostrum and transition milk (referred to as pooled colostrum), as was the standard practice on the dairy farm. The pooled colostrum was collected from the other dairy cows on the farm 0 to 4 d postpartum and stored at 4°C for less than 12 h. Blood was sampled from calves before the first feeding and at 1, 2, 3, and 7 d after birth. Levels of total solids, total protein, and IgG were higher in the dam colostrum than in the pooled colostrum. At birth, there were no differences between the calf groups for any measurements, and all calves had very low IgG levels. After receiving colostrum, the glucose, plasma γ-glutamyl transferase, serum total protein, and IgG concentrations increased significantly in all calves. There were no differences in any blood measurements at any time point between the pairs of group A and group B calves that received colostrum from the same cow except for the IgG concentration 2 d after birth. However, the group A calves had a higher total serum protein level and IgG concentration than the group C calves for all the time points after the first feeding. The group B calves had a higher IgG concentration than the group C calves on d 1, 2, and 7 after birth. Compared with groups A and B, there was no difference in the proportion of calves in group C that failed to have passive immunity transferred adequately based on the IgG threshold (<10 g/L). Thus, the calves receiving identical colostrum from the same cow had the same levels of IgG, and even the pooled colostrum provided sufficient transfer of IgG as the calves were fed within 4 h after birth.