Search results for " immune system"
showing 10 items of 893 documents
Defective Induction of COX-2 Expression by Psoriatic Fibroblasts Promotes Pro-inflammatory Activation of Macrophages
2019
Fibroblasts play an important role as members of the innate immune system through the secretion of COX-2-derived inflammatory mediators such as prostaglandin E-2 (PGE(2)). However, it has been described that dermal fibroblasts behave like mesenchymal stem cells reducing lymphocyte recruitment and dendritic cell activation through PGE(2) release. As the role of fibroblasts in psoriasis remains poorly characterized, in the present study we have evaluated the possible influence of PGE(2) derived from dermal fibroblasts as modulator of the immune response in psoriatic skin. Our results indicate that under inflammatory conditions, psoriatic fibroblasts showed defective induction of COX-2, which …
INNATE IMMUNITY AND INFLAMMATION IN AGEING: A KEY FOR UNDERSTANDING AGE-RELATED DISEASES.
2005
Abstract The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for a…
Innate Immune Cells' Contribution to Systemic Lupus Erythematosus
2019
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies against nuclear antigens, immune complex deposition, and tissue damage in the kidneys, skin, heart and lung. Because of the pathogenic role of antinuclear antibodies and autoreactive T cells in SLE, extensive efforts have been made to demonstrate how B cells act as antibody-producing or as antigen-presenting cells that can prime autoreactive T cell activation. With the discovery of new innate immune cells and inflammatory mediators, innate immunity is emerging as a key player in disease pathologies. Recent work over the last decade has highlighted the importance of innate immun…
Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages
2014
Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS), which metabolizes arginine to nitric oxide (NO) and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the…
Heat-Shock Proteins in Autoimmunity
2013
Heat shock proteins (HSPs), also known as “stress proteins,” are among the highly conserved and immunogenic proteins shared among diverse groups of microbial agents and mammals [1]. Heat and other types of stressful stimuli can increase the cellular expression of HSPs. These proteins have been categorized into different families according to their molecular mass, for example, HSP110, HSP90, HSP70, HSP60, HSP40, HSP20-30, and HSP10 [1–3]. For uniformity, guidelines for the nomenclature of various human HSP families have been proposed [4]. Under physiological conditions, the ubiquitously distributed HSPs maintain the integrity and function of other cellular proteins in stressful conditions. H…
Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4+ Foxp3+ Regulatory T Cells
2017
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly pro…
IL-12 Expands and Differentiates Human Vγ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth
2019
While IL-12 plays a key role in differentiation of protective CD4+ Th1 response, little is known about mechanisms whereby IL-12 differentiates other T-cell populations. Published studies suggest that predominant Vγ2Vδ2 T cells in humans/nonhuman primates (NHP) are a fast-acting T-cell subset, with capacities to rapidly expand and produce Th1 and cytotoxic cytokines in response to phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by Mycobacterium tuberculosis (Mtb) or others. However, whether IL-12 signaling pathway mediates fast-acting and Th1 or anti-microbial features of Vγ2Vδ2 T cells remains poorly defined. Here, we show that IL-12, but not other IL-12 fami…
Prediction of Specific TCR-Peptide Binding From Large Dictionaries of TCR-Peptide Pairs
2019
Abstract The T cell repertoire is composed of T cell receptors (TCR) selected by their cognate MHC-peptides and naive TCR that do not bind known peptides. While the task of distinguishing a peptide-binding TCR from a naive TCR unlikely to bind any peptide can be performed using sequence motifs, distinguishing between TCRs binding different peptides requires more advanced methods. Such a prediction is the key for using TCR repertoires as disease-specific biomarkers. We here used large scale TCR-peptide dictionaries with state-of-the-art natural language processing (NLP) methods to produce ERGO (pEptide tcR matchinG predictiOn), a highly specific classifier to predict which TCR binds to which…
How the knowledge of interactions between meningococcus and the human immune system has been used to prepare effective Neisseria meningitidis vaccines
2015
In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity ofNeisseria meningitidisat a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics). Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in…
Antigen-specific T cells and cytokines detection as useful tool for understanding immunity against zoonotic infections.
2012
Zoonoses include a broad range of diseases, that are becoming of great interest, due to the climate changing, that cause the adaptation of vectors to new niches and environments. Host immune responses play a crucial role in determining the outcome of infections, as documented by expansion of antigen-specific T cells during several zoonotic infections. Thus, understanding of the contribution of antigen-specific T-cell subsets in the host immune response is a powerful tool to evaluate the different immunological mechanisms involved in zoonotic infections and for the development of effective vaccines. In this paper we discuss the role of T cells in some eukaryotic and prokaryotic infectious mo…