抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Cell signaling by receptor-tyrosine kinases

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms. In drosophila antimicrobial responses rely on two signaling pathways: the Toll pathway and the IMD pathway. In mammals there are at least 10 members of the Toll-like receptor (TLR) family that recognize specific components conserved among microorganisms. Activation of the TLRs leads not only to the induction of inflammatory responses but also to the development of antigen-specific adaptive immunity. The TLR-induced inflammatory response is dependent on a common signaling pathway that is mediated by the adaptor molecule MyD88. However, there is evidence for additional pathways that mediate TLR ligand-specific biological responses.

Toll-like receptors.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.

/pdf/myeloid-derived-suppressor-cells-as-regulators-of-the-immune-4w2mvge6zg.pdf

Myeloid-derived suppressor cells as regulators of the immune system.

Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.

https://science.sciencemag.org/content/sci/264/5164/1415.full.pdf

Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins

NF-κB-ISGF3 Transcription Factor Cooperation: Coincidence Detector or Memory Chip?

Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in the absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in the absence of tonic IFN signaling, which triggered expansion of TH17 cells and loss of splenic Treg cells. Reduction of bacterial load by antibiotic treatment averted the TH17 bias and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation.

Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome

A receptor recognition factor exists that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor may itself be a part of a transcription factor or may interact with a transcription factor to cause it to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by IFNα. Additional observations derived from studies with IFNτ are also supportive.

Receptor recognition factor and methods of use thereof

Genotypic variation in the adaptation of potatoes of several maturity classes to the specific climatological conditions of the autumn season, to the high summer temperatures and to water deficit, was studied. Late-maturing cultivars exhibited the highest yielding potential both in the spring and autumn seasons but specific compatibility of cultivars to the autumn was detected. The late-maturing cultivars were more susceptible to high temperatures than were the early ones. However, there were significant differences in susceptibility to high temperatures among cultivars of the same maturity class. Susceptibility to water deficit was similar in the various maturity classes, but there were differences in the susceptibility to drought among cultivars of the same maturity class. High yielding potential generally resulted also in acceptable tuber yields under conditions of water deficit. High temperatures in combination with a water deficit aggravated yield losses, especially in the late-maturing cultivars.

Compatibility of potatoes to contrasting seasonal conditions, to high temperatures and to water deficit: The association with time of maturation and yield potential

Potato plants (Solanum tuberosum L.) of the cultivars Alpha, Cara, Blanka, Desiree and Idit, were exposed to a transient water deficit during tuber growth. Drought stress increased the concentration of solutes as assessed by refractometry and lowered the osmotic potentials as assessed by cryoscopy in both leaf and tuber tissues of the five cultivars. Differences among cultivars, as well as between leaf and tuber tissue of the same cultivar, could indicate variability of the soluble components contributing to the osmotic potential. Differences were noted in the response of the cultivars to the environment in terms of osmotic potentials. Essentially, two types of responses were identified: transient maintenance of lower osmotic potential for 24–48 h after stress relief; and inherently high concentration of solutes and low osmotic potential. The possible advantage of sensitivity to environmental changes is also considered.

David E. Levy

Papers

NF-κB-ISGF3 Transcription Factor Cooperation: Coincidence Detector or Memory Chip?

Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome

Receptor recognition factor and methods of use thereof

Compatibility of potatoes to contrasting seasonal conditions, to high temperatures and to water deficit: The association with time of maturation and yield potential

Osmotic potential of potatoes subjected to a single cycle of water deficit