Immune system modeling

A purified neutral exopolysaccharide (EPS) designated as EPS0142 was obtained from Lactobacillus plantarum JLK0142. EPS0142 consisted of glucose and galactose in an approximate molar ratio of 2.13:1.06 and had a molecular weight of 1.34 × 105  Da. The FT-IR spectrum showed that EPS0142 had a typical polysaccharide absorption pattern. 1 H NMR and 13 C NMR spectra analysis showed the presence of N-acetylated sugar residues. EPS0142 had no toxic effects on RAW 264.7 cells and significantly improved their phagocytic activity and NO secretion in vitro...

Inflammatory bowel disease (IBD) is associated with a number of immune-mediated extra-intestinal manifestations. Over half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid- and dextran sulfate sodium-induced models of colitis...

Vitamin D deficiency and up-regulated TNFα-related signals are reported to be involved in abnormalities including intestinal hyper-permeability, bacterial translocation, systemic/portal endotoxemia, intestinal/adipose tissue/hepatic inflammation, and hepatic steatosis in nonalcoholic steatohepatitis (NASH). This study aims to explore the molecular mechanisms and effects of chronic calcitriol [1,25-(OH)2D3, hormonal form of vitamin D] on gut-adipose tissue-liver axis abnormalities using a high-fat diet (HFD)-fed rat model of NASH...

BACKGROUND: Although both chronic lung disease and HIV are inflammatory diseases common in sub-Saharan Africa, the relationship between systemic inflammation and lung function among people living with HIV (PLWH) in sub-Saharan Africa is not well described. METHODS: We measured lung function (using spirometry) and serum high sensitivity C-reactive protein, IL-6, sCD14 and sCD163 in 125 PLWH on stable antiretroviral therapy and 109 age and sex-similar HIV-uninfected controls in rural Uganda...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is still lack of commercially viable treatment currently. Pien Tze Huang (PZH), a traditional Chinese medicine, has been proved to have anti-inflammatory, neuroprotective, and immunoregulatory effects. This study investigated the possible therapeutic effects of PZH on experimental autoimmune encephalomyelitis (EAE) rats, a classic animal model of MS. Male Lewis rats were immunized with myelin basic protein (MBP) peptide to establish an EAE model and then treated with three doses of PZH...

Objectives: The interaction between HIV and the immune system gives rise to a complex dynamical system. We therefore investigate whether delayed viral rebound after antiretroviral therapy (ART) interruption (ATI) may be due to an individual's viral-immune state being in a region of relative stability, and if so, how this can be extended. Methods: Using a mathematical model duplicating plasma viral levels, HIV DNA and immune homeostatic dynamics for individuals on ART commenced at either primary (PHI) or chronic (CHI) HIV infection, we investigate whether latent reservoir reductions and perturbations in other infected and uninfected memory CD4+ T cell subsets can delay viral rebound...

Inflammation is a hallmark of different central nervous system (CNS) pathologies. It has been linked to neurodegenerative disorders as well as primary and metastatic brain tumors. Microglia, the brain-resident immune cells, are emerging as a central player in regulating key pathways in CNS inflammation. Recent insights into neuroinflammation indicate that blood-borne immune cells represent an additional critical cellular component in mediating CNS inflammation. The lack of experimental systems that allow for discrimination between brain-resident and recruited myeloid cells has previously halted functional analysis of microglia and their blood-borne counterparts in brain malignancies...

Immune synapse (IS) formation by T lymphocytes constitutes a crucial event involved in antigen-specific, cellular and humoral immune responses. After IS formation by T lymphocytes and antigen-presenting cells, the convergence of secretory vesicles toward the microtubule-organizing center (MTOC) and MTOC polarization to the IS are involved in polarized secretion at the synaptic cleft. This specialized mechanism appears to specifically provide the immune system with a fine strategy to increase the efficiency of crucial secretory effector functions of T lymphocytes, while minimizing non-specific, cytokine-mediated stimulation of bystander cells, target cell killing and activation-induced cell death...

BACKGROUND: A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. HYPOTHESIS/OBJECTIVES: To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation...

Sepsis-induced myocardial injury is a well-known cause of mortality. The cholinergic anti-inflammatory pathway (CHAIP) is a physiological mechanism by which the central nervous system regulates immune response through the vagus nerve and acetylcholine; the α7-nicotinic acetylcholine receptor (α7nAChR) is the main component of CHAIP; GTS-21, a synthetic α7nAChR selective agonist, has repeatedly shown its powerful anti-inflammatory effect. However, little is known about its effect on LPS-induced myocardial injury...

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of all or part of the digestive tract. Nutraceuticals include bioactive compounds such as polyphenols with anti-inflammatory activities, thus these products have the potential to treat chronic inflammatory diseases. We have emphasized the role of nutraceuticals in ameliorating the symptoms of IBD in rodent models of human IBD through modulation of key pathogenic mechanisms including dysbiosis, oxidative stress, increased inflammatory cytokines, immune system dysregulation, and inflammatory cell signaling pathways...

Tissue engineering and regenerative medicine, facilitated by biomaterial-based therapies, hold promise for the repair, replacement, or regeneration of damaged tissue. The success or failure of all implanted biomaterials, ranging from stainless steel total joint replacements to naturally or synthetically derived skin grafts, is predominantly mediated by macrophages, the primary cell of the innate immune system. In an effort to better assess safety and efficacy of novel biomaterials, evaluating and understanding macrophage-biomaterial interactions is a necessary first step...

Particulate matter (PM) air pollution has been associated with an increase in the incidence of chronic allergic diseases; however, the mechanisms underlying the effect of exposure to natural ambient air pollution in chronic allergic diseases have not been fully elucidated. In the present study, we aimed to investigate the cellular responses induced by exposure to natural ambient air pollution, employing a mouse model of chronic allergy. The results indicated that exposure to ambient air pollution significantly increased the number of eosinophils in the nasal mucosa...

Lymph nodes are an important part of the immune system. They filter the lymphatic fluid as it is transported from the tissues before being returned to the blood stream. The fluid flow through the nodes influences the behaviour of the immune cells that gather within the nodes and the structure of the node itself. Measuring the fluid flow in lymph nodes experimentally is challenging due to their small size and fragility. In this paper, we present high resolution X-ray computed tomography images of a murine lymph node...

OBJECTIVE: Modeling and analysis of cell population dynamics enhance our understanding of cancer. Here we introduce and explore a new model that may apply to many tissues. ANALYSES: An age-structured model describing coexistence between mutated and ordinary stem cells is developed and explored. The model is transformed into a nonlinear time-delay system governing the dynamics of healthy cells, coupled to a nonlinear differential-difference system describing dynamics of unhealthy cells...

BACKGROUND: Immunoglobulin(Ig)E-associated allergies result from misguided immune responses against innocuous antigens. CD4+ T lymphocytes are critical for initiating and perpetuating that process, yet the crucial factors determining whether an individual becomes sensitized towards a given allergen remain largely unknown. OBJECTIVE: To determine the key factors for sensitization and allergy towards a given allergen. METHODS: We here created a novel human T cell receptor(TCR) and human leucocyte antigen (HLA)-DR1 (TCR-DR1) transgenic mouse model of asthma, based on the human-relevant major mugwort (Artemisia vulgaris) pollen allergen Art v 1 to examine the critical factors for sensitization and allergy upon natural allergen exposure via the airways in the absence of systemic priming and adjuvants...

Given the many cell types and molecular components of the human immune system, along with vast variations across individuals, how should we go about developing causal and predictive explanations of immunity? A central strategy in human studies is to leverage natural variation to find relationships among variables, including DNA variants, epigenetic states, immune phenotypes, clinical descriptors, and others. Here, we focus on how natural variation is used to find patterns, infer principles, and develop predictive models for two areas: (a) immune cell activation-how single-cell profiling boosts our ability to discover immune cell types and states-and (b) antigen presentation and recognition-how models can be generated to predict presentation of antigens on MHC molecules and their detection by T cell receptors...

The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings...

Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction...

Detrimental effects of air pollution with fine dust (particulate matter ≤2.5 μm in aerodynamic diameter, or PM2.5 ) on the systemic circulation and the left heart have been studied intensely during the past decade. In comparison, knowledge regarding the effects of exposure to air pollution with PM2.5 on the pulmonary vasculature and the right heart lags far behind. A report on severe lung disease and right heart failure in coal miners was published nearly 170 years ago. However, today, we still do not have a clear picture of how the effect of air pollution on the pulmonary circulation or the right heart should be viewed from a clinical, mechanistic biological, therapeutic, or economic angle...