Search results for " immune system"
showing 10 items of 893 documents
Mechanisms of immunosenescence
2009
Abstract On April 7,8, 2009 a Symposium entitled "Pathophysiology of Successful and Unsuccessful Ageing" took place in Palermo, Italy. Here, the lectures of G. Pawelec, D. Dunn-Walters and. G. Colonna-Romano on T and B immunosenescence are summarized. In the elderly, many alterations of both innate and acquired immunity have been described. Alterations to the immune system in the older person are generally viewed as a deterioration of immunity, leading to the use of the catch-all term immunosenescence. Indeed, many immunological parameters are often markedly different in elderly compared to young people, and some, mostly circumstantial, evidence suggests that retained function of both innat…
Tolerogenic Dendritic Cells for Regulatory T Cell Induction in Man.
2015
Dendritic cells are (DC) highly specialized professional antigen-presenting cells (APC) that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively we…
New Insight into Immunity and Immunopathology of Rickettsial Diseases
2011
Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the generaRickettsia,Orientia,Ehrlichia, andAnaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecularRickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene exp…
IL-2 Expression in Activated Human Memory FOXP3(+) Cells Critically Depends on the Cellular Levels of FOXP3 as Well as of Four Transcription Factors …
2012
The human CD4(+)FOXP3(+) T cell population is heterogeneous and consists of various subpopulations which remain poorly defined. Anergy and suppression are two main functional characteristics of FOXP3(+)Treg cells. We used the anergic behavior of FOXP3(+)Treg cells for a better discrimination and characterization of such subpopulations. We compared IL-2-expressing with IL-2-non-expressing cells within the memory FOXP3(+) T cell population. In contrast to IL-2-non-expressing FOXP3(+) cells, IL-2-expressing FOXP3(+) cells exhibit intermediate characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR, and Helios. Besides lower levels of FOXP3, they also have higher levels…
Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space
2019
Immunodominant T cell epitopes preferentially targeted in multiple individuals are the critical element of successful vaccines and targeted immunotherapies. However, the underlying principles of this "convergence" of adaptive immunity among different individuals remain poorly understood. To quantitatively describe epitope immunogenicity, here we propose a supervised machine learning framework generating probabilistic estimates of immunogenicity, termed "immunogenicity scores," based on the numerical features computed through sequence-based simulation approximating the molecular scanning process of peptides presented onto major histocompatibility complex (MHC) by the human T cell receptor (T…
γδ T Cells Cross-Link Innate and Adaptive Immunity in Mycobacterium tuberculosis Infection
2011
Protective immunity against mycobacterial infections such asMycobacterium tuberculosisis mediated by interactions between specific T cells and activated antigen presenting cells. To date, many aspects of mycobacterial immunity have shown that innate cells could be the key elements that substantially may influence the subsequent adaptive host response. During the early phases of infection, innate lymphocyte subsets play a pivotal role in this context. Here we summarize the findings of recent investigations onγδT lymphocytes and their role in tuberculosis immunity.
Memory CD8+ T Cell Protection From Viral Reinfection Depends on Interleukin-33 Alarmin Signals
2019
Memory CD8+ cytotoxic T lymphocytes (CTLs) can protect against viral reinfection. However, the signals driving rapid memory CTL reactivation have remained ill-defined. Viral infections can trigger the release of the alarmin interleukin-33 (IL-33) from non-hematopoietic cells. IL-33 signals through its unique receptor ST2 to promote primary effector expansion and activation of CTLs. Here, we show that the transcription factor STAT4 regulated the expression of ST2 on CTLs in vitro and in vivo in primary infections with lymphocytic choriomeningitis virus (LCMV). In the primary antiviral response, IL-33 enhanced effector differentiation and antiviral cytokine production in a CTL-intrinsic manne…
Macrophage: SHIP of Immunity
2014
Immunology. Why does it exist? Two words. Cure disease. People get diseases. “Test tubes” do not. People fund immunologists for solutions to their health problems. But, immunologists often study leukocytes in test tubes – the laboratory – away from diseases. Why? Because much can be learned from analyzing cellular biochemistry and behaviors in vitro that cannot be ascertained when leukocytes are in animals. At the same time, isolated leukocyte reactions often do not reflect how the immune system operates as a unit. So, it is critical to verify in vitro observations in vivo. Among leukocytes, macrophages are the central initiating and directing element in immune systems, and serve this role …
Apoptotic-like Leishmania exploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination
2015
Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed--in contrast to viable parasites--that apoptotic-like parasites enter an LC3(+), autophagy-like compartment. The compartm…
Reduced CD27−IgD− B Cells in Blood and Raised CD27−IgD− B Cells in Gut-Associated Lymphoid Tissue in Inflammatory Bowel Disease
2019
The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD. Here we analyzed B cells in blood of patients with Crohn's disease (CD) and ulcerative colitis (UC) with a range of disease activities. We analyzed the frequencies of known B cell subsets in blood and observed a consistent reduction in the proportion of CD27−IgD− B cells expressing all Ig isotypes in the blood in IBD (independent o…