The Role of the Spleen in Lymphocyte Migration

In all species studied so far it was found that more lymphocytes migrate to the spleen than to all the lymph nodes together. Specific molecules on lymphocytes and endothelial cells regulate their entry into lymph nodes, but none of the known molecules play a role in homing to the spleen. The splenic compartments, comprising the red pulp, marginal zone, periarterial lymphatic sheath (PALS) and follicles, all show different kinetics for migrating lymphocytes. By combining 51Cr lymphocyte labeling with morphometry and two color immunohistochemistry, the migratory route of lymphocyte subsets can be followed through the spleen and absolute numbers of lymphocytes calculated in each compartment. T lymphocytes home preferentially to the PALS and B lymphocytes home not only to follicles but also in large numbers to the marginal zone and red pulp. CD4+ and CD8+ lymphocytes migrate similarly at early time points, but at 24 hours CD4+ lymphocytes are preferentially found in the PALS with CD8+ lymphocytes in the red pulp and marginal zone. The functional significance of the different routes of lymphocytes through the spleen has yet to be defined in relationship to specific immune functions and regulatory factors on splenic lymphocyte homing

What is the clinical relevance of different lung compartments?

The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense

Carbon radio recombination lines from gigahertz to megahertz frequencies towards Orion A

Context. The combined use of carbon radio recombination lines (CRRLs) and the 158 $\mu$m-[CII] line is a powerful tool for the study of the energetics and physical conditions (e.g., temperature and density) of photodissociation regions (PDRs). However, there are few observational studies that exploit this synergy. Aims. Here we explore the relation between CRRLs and the 158 $\mu$m-[CII] line in light of new observations and models. Methods. We present new and existing observations of CRRLs in the frequency range 0.15--230 GHz with ALMA, VLA, the GBT, Effelsberg 100m, and LOFAR towards Orion~A (M42). We complement these observations with SOFIA observations of the 158 $\mu$m-[CII] line. We studied two PDRs: the foreground atomic gas, known as the Veil, and the dense PDR between the HII region and the background molecular cloud. Results. In the Veil we are able to determine the gas temperature and electron density, which we use to measure the ionization parameter and the photoelectric heating efficiency. In the dense PDR, we are able to identify a layered PDR structure at the surface of the molecular cloud to the south of the Trapezium cluster. There we find that the radio lines trace the colder portion of the ionized carbon layer, the C$^{+}$/C/CO interface. By modeling the emission of the $158$~$\mu$m-[CII] line and CRRLs as arising from a PDR we derive a thermal pressure $>5\times10^{7}$ K cm$^{-3}$ and a radiation field $G_{0}\approx10^{5}$ close to the Trapezium. Conclusions. This work provides additional observational support for the use of CRRLs and the 158 $\mu$m-[CII] line as complementary tools to study dense and diffuse PDRs, and highlights the usefulness of CRRLs as probes of the C$^{+}$/C/CO interface.Comment: 18 pages, 16 figures, accepted for publication in A&

The N-terminal domains of syntaxin 7 and vti1b form three-helix bundles that differ in their ability to regulate SNARE complex assembly

The SNAREs syntaxin 7, syntaxin 8, vti1b, and endobrevin/VAMP8 function in the fusion of late endosomes. Although the core complex formed by these SNAREs is very similar to the neuronal SNARE complex, it differs from the neuronal complex in that three of the four SNAREs contain extended N-terminal regions of unknown structure and function. Here we show that the N- terminal regions of syntaxin 7, syntaxin 8, and vti1b contain well folded a-helical domains. Multidimensional NAIR spectroscopy revealed that in syntaxin 7 and vti1b, the domains form three-helix bundles resembling those of syntaxin 1, Sso1p, and Vam3p. The three-helix bundle domain of vti1b is the first of its kind identified in a SNARE outside the syntaxin family. Only syntaxin 7 adopts a closed conformation, whereas in vti1b and syntaxin 8, the N-terminal domains do not interact with the adjacent SNARE motifs. Accordingly, the rate of SNARE complex assembly is retarded about 7-fold when syntaxin 7 contains its N-terminal domain, whereas the N-terminal domains of vti1b and syntaxin 8 have no influence on assembly kinetics. We conclude that three-helix bundles represent a common fold for SNARE N- terminal domains, not restricted to the syntaxin family. However, they differ in their ability to adopt closed conformations and thus to regulate the assembly of SNARE complexes

Relationship between the unbinding and main transition temperatures of phospholipid bilayers under pressure

Using neutron diffraction and a specially constructed high pressure cell suitable for aligned multibilayer systems, we have studied, as a function of pressure, the much observed anomalous swelling regime in dimyristoyl- and dilauroyl-phosphatidylcholine bilayers, DMPC and DLPC, respectively. We have also reanalyzed data from a number of previously published experiments and have arrived at the following conclusions. (a) The power law behavior describing anomalous swelling is preserved in all PC bilayers up to a hydrostatic pressure of 240 MPa. (b) As a function of increasing pressure there is a concomitant decrease in the anomalous swelling of DMPC bilayers. (c) For PC lipids with hydrocarbon chains ≥13 carbons the theoretical unbinding transition temperature T* is coupled to the main gel-to-liquid crystalline transition temperature TM. (d) DLPC is intrinsically different from the other lipids studied in that its T* is not coupled to TM. (e) For DLPC bilayers we predict a hydrostatic pressure (>290MPa) where unbinding may occur

Expanding bubbles in Orion A: [CII] observations of M42, M43, and NGC 1977

The Orion Molecular Cloud is the nearest massive-star forming region. Massive stars have profound effects on their environment due to their strong radiation fields and stellar winds. Velocity-resolved observations of the [CII] $158\,\mu\mathrm{m}$ fine-structure line allow us to study the kinematics of UV-illuminated gas. Here, we present a square-degree-sized map of [CII] emission from the Orion Nebula complex obtained by the upGREAT instrument onboard SOFIA, covering the entire Orion Nebula (M42) plus M43 and the nebulae NGC 1973, 1975, and 1977. We compare the stellar characteristics of these three regions with the kinematics of the expanding bubbles surrounding them. The bubble blown by the O7V star $\theta^1$ Ori C in the Orion Nebula expands rapidly, at $13\,\mathrm{km\,s^{-1}}$. Simple analytical models reproduce the characteristics of the hot interior gas and the neutral shell of this wind-blown bubble and give us an estimate of the expansion time of $0.2\,\mathrm{Myr}$. M43 with the B0.5V star NU Ori also exhibits an expanding bubble structure, with an expansion velocity of $6\,\mathrm{km\,s^{-1}}$. Comparison with analytical models for the pressure-driven expansion of H\,{\sc ii} regions gives an age estimate of $0.02\,\mathrm{Myr}$. The bubble surrounding NGC 1973, 1975, and 1977 with the central B1V star 42 Orionis expands at $1.5\,\mathrm{km\,s^{-1}}$, likely due to the over-pressurized ionized gas as in the case of M43. We derive an age of $0.4\,\mathrm{Myr}$ for this structure. We conclude that the bubble of the Orion Nebula is driven by the mechanical energy input by the strong stellar wind from $\theta^1$ Ori C, while the bubbles associated with M43 and NGC 1977 are caused by the thermal expansion of the gas ionized by their central later-type massive stars

'A habitual disposition to the good': on reason, virtue and realism

Amidst the crisis of instrumental reason, a number of contemporary political philosophers including Jürgen Habermas have sought to rescue the project of a reasonable humanism from the twin threats of religious fundamentalism and secular naturalism. In his recent work, Habermas defends a post-metaphysical politics that aims to protect rationality against encroachment while also accommodating religious faith within the public sphere. This paper contends that Habermas’ post-metaphysical project fails to provide a robust alternative either to the double challenge of secular naturalism and religious fundamentalism or to the ruthless instrumentalism that underpins capitalism. By contrast with Habermas and also with the ‘new realism’ of contemporary political philosophers such as Raymond Geuss or Bernard Williams, realism in the tradition of Plato and Aristotle can defend reason against instrumental rationality and blind belief by integrating it with habit, feeling and even faith. Such metaphysical–political realism can help develop a politics of virtue that goes beyond communitarian thinking by emphasising plural modes of association (not merely ‘community’), substantive ties of sympathy and the importance of pursuing goodness and mutual flourishing