535,456 research outputs found
Has HIV evolved to induce immune pathogenesis?
Human immunodeficiency virus (HIV) induces a chronic generalized activation of the immune system, which plays an important role in the pathogenesis of AIDS. This ability of the virus might either be an evolved (adaptive) trait or a coincidental side effect of jumping to a new host species. We argue that selection favours the ability of HIV to induce immune activation at the local sites of infection (e.g. lymph follicles) but not at the systemic level. Immune activation increases the supply of susceptible target cells; however, mutations that increase systemic immune activation benefit all virus variants equally and are therefore selectively neutral. We thus conclude that the generalized immune acti- vation that is probably responsible for pathogenesis is probably not directly under selection
Activation of effector immune cells promotes tumor stochastic extinction: A homotopy analysis approach
In this article we provide homotopy solutions of a cancer nonlinear model
describing the dynamics of tumor cells in interaction with healthy and effector
immune cells. We apply a semi-analytic technique for solving strongly nonlinear
systems - the Step Homotopy Analysis Method (SHAM). This algorithm, based on a
modification of the standard homotopy analysis method (HAM), allows to obtain a
one-parameter family of explicit series solutions. By using the homotopy
solutions, we first investigate the dynamical effect of the activation of the
effector immune cells in the deterministic dynamics, showing that an increased
activation makes the system to enter into chaotic dynamics via a
period-doubling bifurcation scenario. Then, by adding demographic stochasticity
into the homotopy solutions, we show, as a difference from the deterministic
dynamics, that an increased activation of the immune cells facilitates cancer
clearance involving tumor cells extinction and healthy cells persistence. Our
results highlight the importance of therapies activating the effector immune
cells at early stages of cancer progression
miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice
Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ~22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation
Chapter Five. Systematic review results by biomarker classifications
5.1 Markers of Absorption and Permeability Overview
5.2 Markers of Absorption
5.3 Markers of Permeability
5.4 Markers of Digestion
5.5 Markers of Intestinal Inflammation and Intestinal Immune Activation
5.6 Markers of Systemic Inflammation and Systemic Immune Activation
5.7 Markers of Microbial Drivers
5.8 Markers of Nonspecific Intestinal Injury
5.9 Markers of Extra-Small Intestinal Function
5.10 Relationships Between Markers of EED, Including Histopathology
5.11 Relationships between EED Biomarkers and Growth or Other Outcomes of Interesthttps://digitalcommons.wustl.edu/tropicalenteropathybook/1006/thumbnail.jp
The microglial "activation" continuum: from innate to adaptive responses
Microglia are innate immune cells of myeloid origin that take up residence in the central nervous system (CNS) during embryogenesis. While classically regarded as macrophage-like cells, it is becoming increasingly clear that reactive microglia play more diverse roles in the CNS. Microglial "activation" is often used to refer to a single phenotype; however, in this review we consider that a continuum of microglial activation exists, with phagocytic response (innate activation) at one end and antigen presenting cell function (adaptive activation) at the other. Where activated microglia fall in this spectrum seems to be highly dependent on the type of stimulation provided. We begin by addressing the classical roles of peripheral innate immune cells including macrophages and dendritic cells, which seem to define the edges of this continuum. We then discuss various types of microglial stimulation, including Toll-like receptor engagement by pathogen-associated molecular patterns, microglial challenge with myelin epitopes or Alzheimer's β-amyloid in the presence or absence of CD40L co-stimulation, and Alzheimer disease "immunotherapy". Based on the wide spectrum of stimulus-specific microglial responses, we interpret these cells as immune cells that demonstrate remarkable plasticity following activation. This interpretation has relevance for neurodegenerative/neuroinflammatory diseases where reactive microglia play an etiological role; in particular viral/bacterial encephalitis, multiple sclerosis and Alzheimer disease
HIV-1 Tat exacerbates lipopolysaccharide-induced cytokine release via TLR4 signaling in the enteric nervous system
The loss of gut epithelium integrity leads to translocation of microbes and microbial products resulting in immune activation and drives systemic inflammation in acquired immunodeficiency syndrome (AIDS) patients. Although viral loads in HIV patients are significantly reduced in the post-cART era, inflammation and immune activation persist and can lead to morbidity. Here, we determined the interactive effects of the viral protein HIV-1 Tat and lipopolysaccharide (LPS) on enteric neurons and glia. Bacterial translocation was significantly enhanced in Tat-expressing (Tat+) mice. Exposure to HIV-1 Tat in combination with LPS enhanced the expression and release of the pro-inflammatory cytokines IL-6, IL-1β and TNF-α in the ilea of Tat+ mice and by enteric glia. This coincided with enhanced NF-κB activation in enteric glia that was abrogated in glia from TLR4 knockout mice and by knockdown (siRNA) of MyD88 siRNA in wild type glia. The synergistic effects of Tat and LPS resulted in a reduced rate of colonic propulsion in Tat+ mice treated with LPS. These results show that HIV-1 Tat interacts with the TLR4 receptor to enhance the pro-inflammatory effects of LPS leading to gastrointestinal dysmotility and enhanced immune activation
Determinants of a transcriptionally competent environment at the GM-CSF promoter
Granulocyte macrophage-colony stimulating factor
(GM-CSF) is produced by T cells, but not B cells,
in response to immune signals. GM-CSF gene
activation in response to T-cell stimulation requires
remodelling of chromatin associated with the
gene promoter, and these changes do not occur in
B cells. While the CpG methylation status of the
murine GM-CSF promoter shows no correlation with
the ability of the gene to respond to activation, we
find that the basal chromatin environment of the
gene promoter influences its ability to respond to
immune signals. In unstimulated T cells but not B
cells, the GM-CSF promoter is selectively marked
by enrichment of histone acetylation, and association
of the chromatin-remodelling protein BRG1.
BRG1 is removed from the promoter upon activation
concomitant with histone depletion and BRG1
is required for efficient chromatin remodelling and
transcription. Increasing histone acetylation at
the promoter in T cells is paralleled by increased
BRG1 recruitment, resulting in more rapid chromatin
remodelling, and an associated increase in GM-CSF
mRNA levels. Furthermore, increasing histone
acetylation in B cells removes the block in chromatin
remodelling and transcriptional activation
of the GM-CSF gene. These data are consistent
with a model in which histone hyperacetylation
and BRG1 enrichment at the GM-CSF promoter,
generate a chromatin environment competent
to respond to immune signals resulting in gene
activation
Fibronectin in immune responses in organ transplant recipients.
The immune response to an organ allograft involves perpetuation of T cell infiltration and activation. Advances in understanding the mechanisms of T cell activation have placed particular emphasis on the interactions between the T-cell receptor and antigen presenting cells, with little reference to the fact that in vivo activation occurs in the physical context of extracellular matrix proteins (ECM). Indeed, the possibility that ECM proteins may have a determining role in lymphocyte adhesion and tissue localization and function is now becoming more appreciated in view of growing evidence indicating that integrins and other T cell antigens bind ECM components, with some of these components exerting synergistic effects on T-cell activation. This review focuses on the importance of interactions between lymphocytes and fibronectin, a prominent ECM component, for cell migration and function in organ allograft recipients. It explores novel therapeutic approaches based on the assumption that fibronectin represents an active element in the process of T cell activation in the immune cascade triggered by organ transplantation
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