Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle

Neuronal activity within the central nervous system (CNS) strictly depends on homeostasis and therefore does not tolerate uncontrolled entry of blood components. It has been generally believed that under normal conditions, the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB) prevent immune cell entry into the CNS. This view has recently changed when it was realized that activated T cells are able to breach the BBB and the BCSFB to perform immune surveillance of the CNS. Here we propose that the immune privilege of the CNS is established by the specific morphological architecture of its borders resembling that of a medieval castle. The BBB and the BCSFB serve as the outer walls of the castle, which can be breached by activated immune cells serving as messengers for outside dangers. Having crossed the BBB or the BCSFB they reach the castle moat, namely the cerebrospinal fluid (CSF)-drained leptomeningeal and perivascular spaces of the CNS. Next to the CNS parenchyma, the castle moat is bordered by a second wall, the glia limitans, composed of astrocytic foot processes and a parenchymal basement membrane. Inside the castle, that is the CNS parenchyma proper, the royal family of sensitive neurons resides with their servants, the glial cells. Within the CSF-drained castle moat, macrophages serve as guards collecting all the information from within the castle, which they can present to the immune-surveying T cells. If in their communication with the castle moat macrophages, T cells recognize their specific antigen and see that the royal family is in danger, they will become activated and by opening doors in the outer wall of the castle allow the entry of additional immune cells into the castle moat. From there, immune cells may breach the inner castle wall with the aim to defend the castle inhabitants by eliminating the invading enemy. If the immune response by unknown mechanisms turns against self, that is the castle inhabitants, this may allow for continuous entry of immune cells into the castle and lead to the death of the castle inhabitants, and finally members of the royal family, the neurons. This review will summarize the molecular traffic signals known to allow immune cells to breach the outer and inner walls of the CNS castle moat and will highlight the importance of the CSF-drained castle moat in maintaining immune surveillance and in mounting immune responses in the CNS.

Immunologic privilege in the central nervous system and the blood-brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood-brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.

Luxurious Merovingian Textiles Excavated from Burials in the Saint Denis Basilica, France, 6th-7th century

A new examination of the textile fragments found in the Merovingian burials in the basilica of Saint Denis, near Paris, has recently underscored the diversity of fabrics used to make garments in which members of the royal court were buried. Among them, some woolens of fine quality had been dyed with indigotin. The most astonishing fibre found belongs to a mixed textile (not skin) with beaver fibers and wool. Silks contained shellfish purple and in one case kermes? Two dyestuffs associated with royalty and privilege. Along with this was large number of gold threads, probably produced locally and that were used in tablet-woven borders or for embroideries. In addition, several figured silks, of oriental origin, testify to the importance of this "foreign" material and the taste for textiles woven with complex techniques and probably what had originally had beautiful designs. Although none of these designs have been preserved and many colors have been greatly damaged, the technical characteristics of the remnants indicate proveniences as far as Byzantium, Sassanid Persia and the Chinese court. Such precious textiles show the high social status and political power of the Merovingian court, a testament to their ability to access such luxurious and costly textiles through diplomacy and/or trade with other powerful empires. The examination of these rare textiles along with other fine silks and luxury objects from the same period found in France expand our view of the fundamental role of textiles in the political sphere of this early period of European history.

The Personal Foundations of Political Tolerance towards Immigrants

In this paper, we expand previous research on the psychological foundations of attitudes towards immigrants by evaluating the role of the Big Five personality traits with regard to the formation of political tolerance. Following the literature, we elaborate tolerance as a sequential concept of rejection and acceptance to uncover differentiating effects of personality on both immigrant-specific prejudices as well as on the assignment of the right to vote as a pivotal political privilege to this group. Using a representative sample of the Swiss population, with its distinctive history related to the immigration issue, our two-step Heckman selection models reveal that extroverts and people who score low in agreeableness exhibit negative attitudes towards immigrants. At the same time, only openness to experience is significantly connected to the likeliness of granting immigrants the right to vote.