Thermal imprinting modifies adult stress and innate immune responsiveness in the teleost sea bream

The impact of thermal imprinting on the plasticity of the hypothalamic-pituitary-interrenal (HPI) axis and stress response in an adult ectotherm, the gilthead sea bream (Sparus aurata, L.), during its development was assessed. Fish were reared under 4 thermal regimes, and the resulting adults exposed to acute confinement stress and plasma cortisol levels and genes of the HPI axis were monitored. Changes in immune function, a common result of stress, were also evaluated using histomorphometric measurements of melanomacrophages centers (MMCs) in the head kidney and by monitoring macrophage-related transcripts. Thermal history significantly modified the HPI responsiveness in adult sea bream when eggs and larvae were reared at a higher than optimal temperature (HT, 22 degrees C), and they had a reduced amplitude in their cortisol response and significantly upregulated pituitary pomc and head kidney star transcripts. Additionally, after an acute stress challenge, immune function was modified and the head kidney of adult fish reared during development at high temperatures (HT and LHT, 18-22 degrees C) had a decreased number of MMCs and a significant downregulation of dopachrome tautomerase. Thermal imprinting during development influenced adult sea bream physiology and increased plasma levels of glucose and sodium even in the absence of an acute stress in fish reared under a high-low thermal regime (HLT, 22-18 degrees C). Overall, the results demonstrate that temperature during early development influences the adult HPI axis and immune function in a teleost fish.project Lifecycle EU-FP7 [222719]FCT- Foundation for Science and Technology [CCMAR/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Differential and Temporal Immunomodulation of alpha4 Integrins on CD4+ Memory Cells by Bordetella pertussis and Bordetella parapertussis

Pertussis, caused by Bordetella pertussis (B. pertussis), is reemerging worldwide due to vaccine inefficacy. The hallmarks of infection are extreme lymphocytosis and delayed recovery, which are partially associated with pertussis toxin. Lymphocytes migrate to infected tissues using trafficking receptors. Specific combinations of these lymphocyte trafficking receptors are identified for skin and gut but are not well established for lung. This study focused on the effect of pertussis toxin on lung-associated trafficking receptors and tested the hypothesis that pertussis toxin alters dendritic cell imprinting of lung trafficking receptors on T cells, thus delaying resolution of the infection. B. pertussis-infected mice were compared with pertussis toxin-deficient strains. Imprinting of trafficking receptors on allogeneic T cells by dendritic cells derived from Bordetella-infected mice was analyzed by flow cytometry. Mice infected with Bordetella strains showed an increase in mature dendritic cells on day 5 post-infection. Despite their mature phenotype, dendritic cells from B. pertussis infection, were compromised in their ability to imprint lung trafficking receptors on allogenic T cells. These results indicated a pertussis toxin-dependent defect in dendritic cell imprinting of lung trafficking receptors on T cells. In conclusion, this study provides important data for future vaccine development against respiratory pathogens

Developmental Systems Theory as a Process Theory

Griffiths and Russell D. Gray (1994, 1997, 2001) have argued that the fundamental unit of analysis in developmental systems theory should be a process – the life cycle – and not a set of developmental resources and interactions between those resources. The key concepts of developmental systems theory, epigenesis and developmental dynamics, both also suggest a process view of the units of development. This chapter explores in more depth the features of developmental systems theory that favour treating processes as fundamental in biology and examines the continuity between developmental systems theory and ideas about process in the work of several major figures in early 20th century biology, most notable C.H Waddington

Immunopathogenesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. The majority of evidence, derived from genetics, tissue analyses, models, and clinical studies, points to an immune-mediated etiology associated with stromal tissue dysregulation that together propogate chronic inflammation and articular destruction. A pre-RA phase lasting months to years may be characterized by the presence of circulating autoantibodies, increasing concentration and range of inflammatory cytokines and chemokines, and altered metabolism. Clinical disease onset comprises synovitis and systemic comorbidities affecting the vasculature, metabolism, and bone. Targeted immune therapeutics and aggressive treatment strategies have substantially improved clinical outcomes and informed pathogenetic understanding, but no cure as yet exists. Herein we review recent data that support intriguing models of disease pathogenesis. They allude to the possibility of restoration of immunologic homeostasis and thus a state of tolerance associated with drug-free remission. This target represents a bold vision for the future of RA therapeutics

Retinoic acid as a modulator of T cell immunity

Indexación: Scopus. DOAJ.Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity.http://www.mdpi.com/2072-6643/8/6/34

Memory NK cell features exploitable in anticancer immunotherapy

Besides their innate ability to rapidly produce effector cytokines and kill virus-infected or transformed cells, natural killer (NK) cells display a strong capability to adapt to environmental modifications and to differentiate into long-lived, hyperfunctional populations, dubbed memory or memory-like NK cells. Despite significant progress in the field of NK cell-based immunotherapies, some factors including their short life span and the occurrence of a tumor-dependent functional exhaustion have limited their clinical efficacy so that strategies aimed at overcoming these limitations represent one of the main current challenges in the field. In this scenario, the exploitation of NK cell memory may have a considerable potential. This article summarizes recent evidence in the literature on the peculiar features that render memory NK cells an attractive tool for antitumor immunotherapy, including their long-term survival and in vivo persistence, the resistance to tumor-dependent immunosuppressive microenvironment, the amplified functional responses to IgG-opsonized tumor cells, and in vitro expansion capability. Along with highlighting these issues, we speculate that memory NK cell-based adoptive immunotherapy settings would greatly take advantage from the combination with tumor-targeting therapeutic antibodies (mAbs), as a strategy to fully unleash their clinical efficacy

The Geometry of Stimulus Control

Many studies, both in ethology and comparative psychology, have shown that animals react to modifications of familiar stimuli. This phenomenon is often referred to as generalisation. Most modifications lead to a decrease in responding, but to certain new stimuli an increase in responding is observed. This holds for both innate and learned behaviour. Here we propose a heuristic approach to stimulus control, or stimulus selection, with the aim of explaining these phenomena. The model has two key elements. First, we choose the receptor level as the fundamental stimulus space. Each stimulus is represented as the pattern of activation it induces in sense organs. Second, in this space we introduce a simple measure of `similarity' between stimuli by calculating how activation patterns overlap. The main advantage we recognise in this approach is that the generalisation of acquired responses emerges from a few simple principles which are grounded in the recognition of how animals actually perceive stimuli. Many traditional problems that face theories of stimulus control (e.g. the Spence-Hull theory of gradient interaction or ethological theories of stimulus summation) do not arise in the present framework. These problems include the amount of generalisation along different dimensions, peak-shift phenomena (with respect to both positive and negative shifts), intensity generalisation, and generalisation after conditioning on two positive stimuli

The identification of markers of macrophage differentiation in PMA-stimulated THP-1 Cells and monocyte-derived macrophages

Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA) and 1,25-dihydroxyvitamin D3 (VD3) are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD3 and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM). Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr) increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells

Mad Dog Nativism

In his recent book, Concepts: Where Cognitive Science Went Wrong, Jerry Fodor retracts the radical concept-nativism he once defended. Yet that position stood, virtually unchallenged, for more than twenty years. This neglect is puzzling, as Fodor's arguments against concepts being learnable from experience remain unanswered, and nativism has historically been taken very seriously as a response to empiricism's perceived shortcomings. In this paper, I urge that Fodorean nativism should indeed be rejected. I argue, however, that its deficiencies are not so obvious that they can simply be taken for granted. Fodor can counter extant objections by stressing two distinctions: between historicist and counterfactual semantic theories and between explaining reference and explaining concept-acquisition. But, I argue, this victory is pyrrhic. Reformulated as objections to his account qua theory of concept-acquisition, and not qua theory of reference, analogous difficulties are fatal to the Fodorean position