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

Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

/pdf/the-blockade-of-immune-checkpoints-in-cancer-immunotherapy-j2cp4ba5s9.pdf

The blockade of immune checkpoints in cancer immunotherapy

A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.

/pdf/re-epithelialization-and-immune-cell-behaviour-in-an-ex-vivo-3lsvtwo6xm.pdf

Re-epithelialization and immune cell behaviour in an ex vivo human skin model.

Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. However, as we discuss here, recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues. These advances in our understanding have implications for the development of therapeutic strategies that are targeted to modify particular subpopulations of monocytes.

https://courses.washington.edu/conj514/readings/heinecke_reading4.pdf

Monocyte and macrophage heterogeneity

Matrix Metalloproteinases: Regulators of the Tumor Microenvironment

Ubertragbare spongiforme Enzephalopathien (Prionen-Erkrankungen) sind neurodegenerative Erkrankungen des Gehirns. Dazu gehoren Jakob-CreutzfeldErkrankung (CJD), Gerstmann-Straussler-ScheinkerKrankheit und Kuru beim Menschen, bovine spongiforme Enzephalopathie (BSE) beim Rind und Traberkrankheit (Scrapie) beim Schaf. Prionen-Erkrankungen zeichnen sich durch Amyloidablagerungen im Interstitium des Gehirns, in dem ein proteaseresistentes Protein, PrPSc, CSc fur Scrapie nachweisbar ist, aus. Im Gegensatz zum physiologisch vorkommenden zellularen Prionen-Protein (PrPc) ist PrPSc infektios und hat bei der Ubertragung spongiformer Enzephalopathien eine entscheidende Funktion. Diese Enzephalopathien werden daher auch Prionen-Erkrankungen (Prion, PrPSc, fur proteinaceous infectious particle) genannt.

Humane und bovine Keratinozyten exprimieren Prionen-Protein in vitro und in situ

Three major arteries supplying the ulnar nerve in the cubital tunnel are commonly known. However, their vascular territories (angiosomes) have not been described yet. Contrast-enhanced ultrasound was used to identify the angiosomes of posterior ulnar recurrent artery, inferior ulnar collateral artery and superior ulnar collateral artery in 20 fresh, non-frozen human body donors. The arteries were cannulated, and physiologic blood flow was simulated. Contrast agent was applied in each vessel in a randomized sequence, and the length of the contrast-enhancing ulnar nerve segment was measured by a radiologist blinded to the sequence. The angiosome of the posterior ulnar recurrent artery overlaps both other angiosomes. It fully covers the cubital tunnel in 63.6% of specimens. In addition, collateral flow via nerve and muscle branches of the arterial anastomotic network around the elbow (rete articulare cubiti) partly maintains the intra-neural blood flow in the absence of a vascular pedicle. The posterior ulnar recurrent artery is the dominant nutrient vessel of the ulnar nerve in the cubital tunnel. A potential watershed zone exists proximal to the Osborne ligament. Knowledge of these angiosomes may advance surgery of the ulnar nerve in the cubital tunnel.

Angiosomes of the Ulnar Nerve at the Elbow: A Cadaver Trial Using Contrast-Enhanced Ultrasound.

http://www.jidonline.org/article/S0022202X22020802/pdf

136 Asymptomatic Sexually Transmitted Infections Are Commonly Detected in Austrian PrEP-Users

Vale Pandemie?

In dieser Studie wurde die Expression von VEGFR-3 und Podoplanin, zweier neuer Lymphendothel-Marker, an KS Tumor-Zellen in situ und an KS-Zellkulturen untersucht. Mittels immunhistologischer Technik konnten wir zeigen, das spindelformige Zellen in KS Fruh- und Spatstadien positiv fur VEGFR-3 und Podoplanin waren. Die nahere Charakterisierung dieser Zellpopulation durch eine Immunfluoreszenz Doppelfarbung ergab, das diese Zellen auch positiv fur CD31, aber negativ fur CD45 und CD68 waren. Im Gegensatz zu primaren KS-Tumoren, konnte in den KS-Zellkulturen keines der beiden Antigene gefunden werden. Wir schliesen daraus, das die Expression von VEGFR-3 und Podoplanin auf KS Tumor-Zellen ein erster direkter Hinweis auf deren Verwandtschaft oder sogar Abstammung vom lymphatischen Endothel ist. Die Tatsache, das KS-Zellkulturen in vitro keines dieser Antigene exprimieren, spricht fur eine Abstammung dieser Zellen von anderen als KS Tumor-Zellen.

Wolfgang Weninger

Papers

Humane und bovine Keratinozyten exprimieren Prionen-Protein in vitro und in situ

Angiosomes of the Ulnar Nerve at the Elbow: A Cadaver Trial Using Contrast-Enhanced Ultrasound.

136 Asymptomatic Sexually Transmitted Infections Are Commonly Detected in Austrian PrEP-Users

Vale Pandemie?

Kaposi Sarkome sind positiv für VEGFR-3 und Podoplanin: Ein erster direkter Beweis für die Abstammung dieses Tumors vom lymphatischen Endothel