Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells

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Losing the last feather: feather loss as an antipredator adaptation in birds

Birds often lose feathers during predation attempts, and thisability has evolved as a means of escape. Because predatorsare more likely to grab feathers on the rump and the back thanon the ventral side of an escaping bird, we predicted that theformer feathers would have evolved to be relatively looselyattached as an antipredator strategy in species that frequentlydie from predation. We estimated the force required to removefeathers from the rump, back, and breast by pulling featherswith a spring balance from a range of European bird speciesin an attempt to investigate ecological factors associated withease of feather loss during predation attempts. The force requiredto loosen a feather from the rump was less than that requiredto loosen a feather from back, which in turn was less than thatrequired to loosen a feather from the breast. The relative forceneeded to loosen rump feathers compared with feathers from theback and the breast was smaller for prey species preferred bythe most common predator of small passerine birds, the sparrowhawkAccipiter nisus. Likewise, the relative force was also smallerin species with a high frequency of complete tail loss amongfree-living birds, which we used as an index of the frequencyof failed predation attempts. The relative force required toremove feathers from the rump was smaller in species with ahigh frequency of fear screams, another measure of the relativeimportance of predation as a cause of death. Feather loss requiredparticularly little force among solitarily breeding bird speciesthat suffer the highest degree of predation. Antipredator defensein terms of force required to remove feathers from the rumpwas larger in species with a strong antiparasite defense interms of T-cell–mediated immune response. These findingsare consistent with the hypothesis that different defenses areantagonistic and that they are traded off against each other.     

Carbonic anhydrase inhibition blocks skeletogenesis and echinochrome production in Paracentrotus lividus and Heliocidaris tuberculata embryos and larvae

Carbonic anhydrases (CAs) are a family of widely distributed metalloenzymes, involved in diverse physiological processes. These enzymes catalyse the reversible conversion of carbon dioxide to protons and bicarbonate. At least 19 genes encoding for CAs have been identified in the sea urchin genome, with one of these localized to the skeletogenic mesoderm (primary mesenchyme cells, PMCs). We investigated the effects of a specific inhibitor of CA, acetazolamide (AZ), on development of two sea urchin species with contrasting investment in skeleton production, Paracentrotus lividus and Heliocidaris tuberculata, to determine the role of CA on PMC differentiation, skeletogenesis and on non‐skeletogenic mesodermal (NSM) cells. Embryos were cultured in the presence of AZ from the blastula stage prior to skeleton formation and development to the larval stage was monitored. At the dose of 8 mmol/L AZ, 98% and 90% of P. lividus and H. tuberculata embryos lacked skeleton, respectively. Nevertheless, an almost normal PMC differentiation was indicated by the expression of msp130, a PMC‐specific marker. Strikingly, the AZ‐treated embryos also lacked the echinochrome pigment produced by the pigment cells, a subpopulation of NSM cells with immune activities within the larva. Conversely, all ectoderm and endoderm derivatives and other subpopulations of mesoderm developed normally. The inhibitory effects of AZ were completely reversed after removal of the inhibitor from the medium. Our data, together with new information concerning the involvement of CA on skeleton formation, provide evidence for the first time of a possible role of the CAs in larval immune pigment cells.     

The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers

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Modulation of the immune response by Middle East respiratory syndrome coronavirus

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.     

Modelling HIV immune response and validation with clinical data

A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+T-cell help in the generation of CD8+memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients.     

Atrophy of compartments of rat lymph nodes related to an entry of lethally altered lymphocytes

Summary This paper reports the occurrence of an accumulation of lethally altered lymphocytes in the subcapsular sinus of a compartment or compartments of some lymph nodes, an unusual feature best developed in nodes of the mesenteric site in aging athymic animals. Many of these cells are rod-like. In other compartments, similar lymphocytes occurred at various depths in the nodal parenchyma. This was accompanied by the disappearance of a compartment's populations of normal lymphoid cells. The observations reveal that lymphocytes, altered in a tissue, may reach the subcapsular sinus of the draining node compartment and migrate into its parenchyma which then undergoes atrophy. The likely involvement of mast cells is discussed.This work was funded by the Medical Research Council of Canada.     

Low incidence of bronchus-associated lymphoid tissue (BALT) in chronically inflamed human lungs

The relevance of bronchus-associated lymphoid tissue (BALT) in man is still under discussion. Animal experiments indicate that the development of BALT is dependent on microbial stimulation. Therefore, the incidence of BALT was investigated retrospectively in specimens removed during surgical procedures on patients with chronic pulmonary inflammation. All these patients had severe chronic bronchitis and bronchiectasis, but BALT was found in only 8%. In patients with BALT and a malignant tumor, occlusion of a bronchus with poststenotic pneumonia was always present and BALT was observed exclusively in areas peripheral to the occlusion. In man other compartments of the lung must be responsible for the immune function of BALT found in animals. Partly presented at the Congress of the Eur. Respir. Soc, 21.- 26.9.1991 in Brussels. (Abstract: Eur Respir J. 4, Suppl. 14:217p)     

The early postnatal development of the primary immune response in TNP-KLH-stimulated popliteal lymph node in the rat

Summary The popliteal lymph nodes were removed from young rats of various ages five days after a single immunization with TNP-KLH in the hind footpads. Cryostat sections of the lymph nodes were investigated by means of enzyme and immunohistochemical techniques at the light-microscopical level.The presence and localization of anti-TNP antibody-containing cells were examined using a new technique to visualize specific antibodies. Moreover, the development of the lymph nodes following exogenous antigenic stimulation was compared with that of unstimulated lymph nodes.Specific antibody-containing cells could not be found before day 15 after birth, in rats immunized at day 10. From that time these lymphoid cells were located primarily at the border between cortex and medulla. Younger popliteal lymph nodes showed only aspecific immunoglobulin-containing lymphoid cells. With age, the number of specific antibody-containing cells tended to increase. These cells were more mature, according to morphological criteria and were located nearer the medulla.The first primary follicles were seen at day 19, as was the case in unstimulated animals. The first secondary follicles, containing germinal centers, were detected at day 23, whereas in unstimulated popliteal lymph nodes they were never found.Trapping of immune complexes could not be demonstrated before day 33 after birth. The later appearance of this phenomenon might be a consequence of the techniques applied to demonstrate specific antibody-containing cells.Abbreviations PLN popliteal lymph node - FDC follicular dendritic cell - IDC interdigitating cell - HEV high endothelial venule - TNP trinitrophenyl - KLH keyhole limpet hemocyanin - PBS phosphate-buffered saline - GCPC germinal center precursor cell - sIg surface immunoglobulin - cIg cytoplasmic immunoglobulin