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

We describe extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data. Most importantly, we develop methods that allow for linkage between loci. The new model accounts for the correlations between linked loci that arise in admixed populations (“admixture linkage disequilibium”). This modification has several advantages, allowing (1) detection of admixture events farther back into the past, (2) inference of the population of origin of chromosomal regions, and (3) more accurate estimates of statistical uncertainty when linked loci are used. It is also of potential use for admixture mapping. In addition, we describe a new prior model for the allele frequencies within each population, which allows identification of subtle population subdivisions that were not detectable using the existing method. We present results applying the new methods to study admixture in African-Americans, recombination in Helicobacter pylori , and drift in populations of Drosophila melanogaster . The methods are implemented in a program, structure , version 2.0, which is available at http://pritch.bsd.uchicago.edu.

/pdf/inference-of-population-structure-using-multilocus-genotype-4p91nh3fvr.pdf

Inference of Population Structure Using Multilocus Genotype Data: Linked Loci and Correlated Allele Frequencies

Dominant markers such as amplified fragment length polymorphisms (AFLPs) provide an economical way of surveying variation at many loci. However, the uncertainty about the underlying genotypes presents a problem for statistical analysis. Similarly, the presence of null alleles and the limitations of genotype calling in polyploids mean that many conventional analysis methods are invalid for many organisms. Here we present a simple approach for accounting for genotypic ambiguity in studies of population structure and apply it to AFLP data from whitefish. The approach is implemented in the program structure version 2.2, which is available from http://pritch.bsd.uchicago.edu/structure.html.

/pdf/inference-of-population-structure-using-multilocus-genotype-19wwjas2e3.pdf

Inference of population structure using multilocus genotype data: dominant markers and null alleles

Matrix Metalloproteinases: Regulators of the Tumor Microenvironment

Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.

Neutrophil recruitment and function in health and inflammation

Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.

http://science.sciencemag.org/content/sci/303/5663/1532.full.pdf

Neutrophil extracellular traps kill bacteria

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.

/pdf/traces-of-human-migrations-in-helicobacter-pylori-4hiosqhau5.pdf

Traces of human migrations in Helicobacter pylori populations

Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1462-5822.2005.00659.x

Ulrike Reichard

Papers

Neutrophil extracellular traps kill bacteria

Traces of human migrations in Helicobacter pylori populations

Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms

Salmonella typhi, the causative agent of typhoid fever, is approximately 50,000 years old.