Despite the skepticism that once prevailed among immunologists, it is now widely accepted that the normal immune system harbors a T-cell population, called regulatory T cells (Treg cells), specialized for immune suppression. It was first shown that depletion of a T-cell subpopulation from normal rodents produced autoimmune disease. Search for a molecular marker specific for such autoimmune-preventive Treg cells has revealed that the majority, if not all, of them constitutively express the CD25 molecule as depletion of CD25+CD4+ T cells spontaneously evokes autoimmune disease in otherwise normal rodents. The expression of CD25 by Treg cells has made it possible to delineate their developmental pathways, in particular their thymic development, and establish simple in vitro assay for assessing their suppressive activity. The marker and the in vitro assay have helped to identify human Treg cells with similar functional and phenotypic characteristics. Recent efforts have shown that natural Treg cells specifically express the transcription factor Foxp3 and that mutations of the Foxp3 gene produce a variety of immunological diseases in humans and rodents. Specific expression of Foxp3 in natural Treg cells has enabled their functional and developmental characterization by genetic approach. These studies altogether have provided firm evidence for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis. Treg cells are now within the scope of clinical use to treat immunological diseases and control physiological and pathological immune responses.

Regulatory T Cells

Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anat...

Pathophysiology of Sleep Apnea

Exercise Physiology: Energy, Nutrition and Human Performance

Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.

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Inflammation, Oxidative Stress, and Obesity

of antibiotics, whether there was an explicit note in the medical chart in which the physician diagnosed a true bacteremia, and the Centers for Disease Control surveillance criteria for primary bloodstream infection. Agreement between same-strain bacteremia and each definition was examined, based on the assumption that most true infections should be the result of a single strain. The study sample consisted of 42 patients and 106 isolates. Nineteen of the 42 bacteremias (45%) were the same strain. Classification of bacteremias as same-strain correlated poorly with all three clinical assessments (range of percentage agreement, 50%-57%; range of kappa statistic, 0.01-0.15). There were both false-positive and false-negative errors. Patients with three or more positive blood cultures were more likely to have same-strain bacteremia than those with only two positive cultures (11/15 [73%] vs 8/27 [30%], P=.006). Pulsed-field gel electrophoresis was more discriminating than AP PCR (percentage agreement, 83%; kappa, 0.67). The authors concluded that molecular typing correlated poorly with clinical criteria for true bacteremia, suggesting either that true bacteremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true bacteremia. Vancomycin treatment of clinically defined coagulase-negative staphylococcal bacteremia may frequently be unnecessary. FROM: Seo SK, Venkataraman L, DeGirolami PC, Samore MH. Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia. Am J Med 2000;109:697-704.

/pdf/nasal-carriage-as-a-source-of-staphylococcus-aureus-40zkf0m446.pdf

Nasal Carriage as a Source of Staphylococcus aureus Bacteremia

Background
The development of obesity and related disorders, e.g., type II diabetes (T2D), hypertension, and metabolic disturbances is strongly related to increased levels in proinflammatory cytokines (IL-1, IL-6, and TNF-α). Both IL-6 and TNF-α are secreted by adipocytes and their concentration correlates with the percentage and distribution of fat tissue in the body. Both cytokines are the main factors responsible for the induction of acute phase proteins production (e.g., CRP) and to inflammatory state.

/pdf/proinflammatory-cytokines-il-6-and-tnf-a-and-the-development-4dh73ubzzs.pdf

Proinflammatory cytokines Il-6 and TNF-α and the development of inflammation in obese subjects.

Perforin is a glycoprotein responsible for pore formation in cell membranes of target cells. Perforin is able to polymerize and form a channel in target cell membrane. Many research groups focus on the role of perforin in various diseases, immune response to bacterial and viral infections, immune surveillance and immunopathology. In addition, perforin is involved in the pathogenesis of autoimmune diseases and allogeneic transplant rejection. Natural killer (NK) cells and CD8-positive T-cells are the main source of perforin. However, CD4-positive T-cells are also able to express a low amount of perforin, when classic cytotoxicity is ineffective or disturbed.

Polymerized perforin molecules form channels enabling free, non-selective, passive transport of ions, water, small-molecule substances and enzymes. In consequence, the channels disrupt protective barrier of cell membrane and destroy integrity of the target cell. This review will focus on mechanisms of action and structure of perforin. Also, in this review we discuss the problem of abnormal perforin production in diseases such as: hemophagocytic lymphohistiocytosis (HLH), leukemias and lymphomas, infectious diseases and autoimmune diseases. Better understanding of the role of these molecules in health and disease will open a new field of research with possible therapeutic implications.

/pdf/perforin-an-important-player-in-immune-response-l50gjs3xnm.pdf

Perforin: an important player in immune response

Inflammation of forebrain and hindbrain nuclei controlling the sympathetic nervous system (SNS) outflow from the brain to the periphery represents an emerging concept of the pathogenesis of neurogenic hypertension. Angiotensin II (Ang-II) and prorenin were shown to increase production of reactive oxygen species and pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)) while simultaneously decreasing production of interleukin-10 (IL-10) in the paraventricular nucleus of the hypothalamus and the rostral ventral lateral medulla. Peripheral chronic inflammation and Ang-II activity seem to share a common central mechanism contributing to an increase in sympathetic neurogenic vasomotor tone and entailing neurogenic hypertension. Both hypertension and obesity facilitate the penetration of peripheral immune cells in the brain parenchyma. We suggest that renin-angiotensin-driven hypertension encompasses feedback and feedforward mechanisms in the development of neurogenic hypertension while low-intensity, chronic peripheral inflammation of any origin may serve as a model of a feedforward mechanism in this condition.

/pdf/brain-inflammation-and-hypertension-the-chicken-or-the-egg-3jxud6ukz3.pdf

Brain inflammation and hypertension: the chicken or the egg?

The prevalence of obesity in children and adolescents has been increasing worldwide. As in adults, childhood obesity is closely related to hypertension, dyslipidemia, type 2 diabetes, and insulin resistance (IR) syndrome. Moreover, obese children have been found to be at increased risk of becoming obese adults. Obese children and adolescents tend to develop serious medical and psychosocial complications and also are at greater risk morbidity and mortality in adulthood. The molecular basis of the pathogenesis of obesity-linked disorders has not been fully elucidated. Adipose tissue serves not only as an energy storage organ, but also as an endocrine organ. It releases many factors with autocrine, paracrine and endocrine functions. Adipokines such as leptin, resistin, tumor necrosis factor-α, interleukin-6, adipsin, visfatin, and adiponectin are biologically active molecules produced by adipose tissue. They play a role in energy homeostasis, and in glucose and lipid metabolism. Adiponectin level, unlike that of other adipocytokines, is decreased in obesity and increased after weight reduction. Adiponectin has been associated with both central obesity and increased visceral adipose tissue and it has anti-inflammatory, anti-atherogenic, and potent insulin-sensitizing (anti-diabetic) effects.

/pdf/adiponectin-as-a-biomarker-of-the-metabolic-syndrome-in-1q33ck64qv.pdf

Adiponectin as a biomarker of the metabolic syndrome in children and adolescents

Under normal conditions, neutrophils are restricted from trafficking into the brain parenchyma and cerebrospinal fluid by the presence of the brain–blood barrier (BBB). Yet, infiltration of the central nervous system (CNS) by neutrophils is a well-known phenomenon in the course of different pathological conditions, e.g., infection, trauma or neurodegeneration. Different studies have shown that neutrophil products, i.e., free oxygen radicals and proteolytic enzymes, play an important role in the pathogenesis of BBB damage. It was recently observed that accumulating granulocytes may release neutrophil extracellular traps (NETs), which damage the BBB and directly injure surrounding neurons. In this review, we discuss the emerging role of NETs in various pathological conditions affecting the CNS.

/pdf/the-brain-entangled-the-contribution-of-neutrophil-4dtug2esi9.pdf

Urszula Demkow

Papers

Proinflammatory cytokines Il-6 and TNF-α and the development of inflammation in obese subjects.

Perforin: an important player in immune response

Brain inflammation and hypertension: the chicken or the egg?

Adiponectin as a biomarker of the metabolic syndrome in children and adolescents

The Brain Entangled: The Contribution of Neutrophil Extracellular Traps to the Diseases of the Central Nervous System.