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Showing posts with label Pathogens. Show all posts
Showing posts with label Pathogens. Show all posts

Tuesday, June 4, 2019

Molecular Basis of Tolerance and Immunity to Antigens.



The intestinal immune system has to discriminate between harmful and beneficial antigens. Although strong protective immunity is essential to prevent invasion by pathogens, equivalent responses against dietary proteins or commensal bacteria can lead to chronic disease. These responses are normally prevented by a complex interplay of regulatory mechanisms. This article reviews the unique aspects of the local microenvironment of the intestinal immune system and discuss how these promote the development of regulatory responses that ensure the maintenance of homeostasis in the gut.



The intestinal immune system is the largest and most complex part of the immune system. Not only does it encounter more antigen than any other part of the body, but it must also discriminate clearly between invasive organisms and harmless antigens, such as food proteins and commensal bacteria. Most human pathogens enter the body through a mucosal surface, such as the intestine, and strong immune responses are required to protect this physiologically essential tissue. In addition, it is important to prevent further dissemination of such infections. By contrast, active immunity against non-pathogenic materials would be wasteful, and hypersensitivity responses against dietary antigens or commensal bacteria can lead to inflammatory disorders such as Coeliac Disease and Crohn's Disease, respectively. As a result, the usual response to harmless gut antigens is the induction of local and systemic immunological tolerance, known as oral tolerance. In addition to its physiological importance, this phenomenon can be exploited for the immunotherapy of autoimmune and inflammatory diseases, but it is also an obstacle to the development of recombinant oral vaccines. For these reasons, there is great interest in the processes that determine the immunological consequences of oral administration of antigen. To some extent, this discrimination between harmful and harmless antigens also occurs in other parts of the immune system, as it partly results from inherent properties of the antigen and associated adjuvants. Nevertheless, it has been proposed that there are also specific features of mucosal tissues that favour the induction of tolerance, the production of immunoglobulin A antibodies and, to a lesser extent, T helper 2 (TH2)-cell responses. Several features of mucosal tissues might contribute to these effects, including a unique ontogeny and anatomical patterning, specialized cells and organs that are involved in the uptake of antigen, distinctive subsets of antigen-presenting cells (APCs) and several unusual populations of B and T cells. In addition, the migration of lymphocytes to the intestine is controlled by a series of unique adhesion molecules and chemokine receptors.

This review article discusses the anatomical factors which determine the special nature of small intestinal immune responses, and the unique processes and cells involved in the uptake and presentation of antigen to T cells in the gut. In particular, it focuses on the local factors that determine the behaviour of APCs and T cells in the gut and discuss recent evidence that challenges the conventional dogma that Peyer’s patches are the only site for the initiation of mucosal immunity and tolerance.

It also focuses on the small intestine, as this tissue has been studied in most detail and it contains the largest proportion of immune cells in the gut. However, the reader should be aware that each compartment of the intestine, from the oropharynx to the stomach and to the rectum, has its own specializations, which might have individual effects on immune regulation in response to local antigens.
  • The intestinal immune system is an anatomically and functionally distinct compartment, in which a careful distinction must be made between harmful antigens, such as invasive pathogens, and harmless antigens, such as dietary proteins or commensal bacteria.
  • The default response to harmless antigens is the induction of tolerance. A breakdown in this physiological process can lead to disease.
  • Immune responses and tolerance in the gut are initiated in organized lymphoid organs, such as the Peyer's patches and mesenteric lymph nodes (MLNs). The mucosa contains effector or regulatory cells that migrate there selectively, from the MLNs, in the lymph and bloodstream under the control of α4β7 integrins and the chemokine receptor CCR9.
  • Pathogens might enter the intestinal immune system through M cells in the follicle-associated epithelium of the Peyer's patches, whereas soluble antigens might gain access predominantly through the normal epithelium that covers the villus mucosa.
  • Peyer's patches, lamina propria and MLNs contain unusual populations of dendritic cells (DCs), some of which are characterized by the production of interleukin-10 (IL-10) and which polarize T cells to an IL-4-, IL-10- and transforming growth factor-β (TGF-β)-producing 'regulatory' phenotype.
  • Genetically determined factors, together with luminal bacteria, might act on epithelial and stromal components of the intestinal mucosa to produce a local microenvironment that is dominated by the constitutive production of prostaglandin E2 (PGE2), TGF-β and IL-10. Under physiological conditions, this favours the differentiation of regulatory DCs and T cells, which leads to systemic tolerance and/or immunoglobulin-A production.

Thursday, November 9, 2017

Gut Bacteria And The Brain: Are We Controlled By Microbes?

Although the interaction between our brain and gut has been studied for years, its complexities run deeper than initially thought. It seems that our minds are, in some part, controlled by the bacteria in our bowels.


The gut has defenses against pathogens, but, at the same time, it encourages the survival and growth of "healthy" gut bacteria.

The vast majority of these single-celled visitors are based in the colon, where no less than 1 trillion reside in each gram of intestinal content.

Estimating the number of bacterial guests in our gut is challenging; to date, the best guess is that 40 trillion bacteria call our intestines home - partially dependent on the size of your last bowel movement (poop's major ingredient is bacteria).




How much sway can a microbe hold? Bacterial influence over human psychology is slowly coming
into focus.

Saturday, September 3, 2016

Zika Virus — Reigniting The TORCH

The recent association between Zika virus (ZIKV) infection during pregnancy and fetal microcephaly has led to a renewed interest in the mechanisms by which vertically transmitted microorganisms reach the fetus and cause congenital disease. In this Opinion article, we provide an overview of the structure and cellular composition of the human placenta and of the mechanisms by which traditional 'TORCH' pathogens (Toxoplasma gondii, other, rubella virus, cytomegalovirus and herpes simplex virus) access the fetal compartment. Based on our current understanding of ZIKV pathogenesis and the developmental defects that are caused by fetal ZIKV infection, ZIKV should be considered a TORCH pathogen and future research and public health measures should be planned and implemented accordingly.

Zika virus (ZIKV), a member of the Flaviviridae family of RNA viruses, was first isolated in the Zika forest in Uganda in 1947.


Routes used by TORCH pathogens to overcome the placental barrier. Vertical
transmission and congenital disease induced by ZIKV.

Tuesday, June 21, 2016

Antimicrobial resistance: a collection of reviews and research papers from Nature journals

Resistance to antimicrobials is a global problem of increasing importance. Pathogens rapidly develop mutations that render current treatments ineffective. For example, resistance to carbapenems, one of the ‘last lines’ of antibiotics, is widespread and has been observed in numerous countries; resistance to artemisinin, the gold standard in malaria treatment, has also emerged. Our current arsenal of antimicrobial agents thus has a limited lifespan and new drugs are urgently needed. Tackling this resistance will require a deep understanding of microbial infections and the mechanisms through which resistance arises, as well as concerted efforts between academia and industry aimed at developing novel antimicrobial agents.

This collection consists of Reviews, Research articles, and News and Comment articles from several Nature journals, describing how antibiotic resistance emerges and detailing strategies through which new antimicrobial compounds are being discovered.



Source: nature

Sunday, June 19, 2016

Food Pathogen Detection via Handheld 'Nanoflower' Biosensor

At present, harmful pathogens in food are mostly only discovered when people get sick. Earlier detection - preferably before food reaches consumers - could prevent many cases of foodborne illness and save the cost and effort involved in food recalls. Now, a team working toward solving this problem has developed a portable biosensor based on "nanoflowers" that detects harmful bacteria.

The new technology is the work of researchers at Washington State University (WSU) in Pullman, who describe how they developed and tested it in a paper published in the journal Small.

Even tiny amounts of harmful bacteria and other microbes can give rise to serious health risks, but the available sensor technology is unable to detect them easily and quickly in small quantities.

The key challenge in solving this problem is finding a way to detect the faint chemical signals that the harmful microbes emit at the molecular level.


The nanoflower biosensor detects tiny chemical signals emitted by bacteria and amplifies them so they
can be picked up easily with a simple handheld pH meter.

Thursday, April 28, 2016

Molecular Diagnostics in the Microbiology Laboratory

A look at some of the newest generation ‘load and go’ molecular microbiology analyzers.

For decades, pathogens have been isolated and grown in blood cultures, and detected using microscopes, serology and biochemical techniques. However the last few years have seen a revolution in modern microbiology.

The above tests still form the core work of most routine microbiology labs, but modern analytical techniques such as molecular diagnostics and mass spectrometry are increasingly being incorporated, to varying degrees, in laboratories around the world.

Molecular diagnostics refers to the analysis of nucleic acid from DNA or RNA. In the clinical microbiology lab, scientists are looking for the nucleic acid of microorganisms to confirm or exclude a diagnosis.

The molecular diagnostic work undertaken in the lab can vary from a simple, manual monoplex polymerase chain reaction (PCR) based test to complex automated, multiplex testing (testing for multiple pathogens simultaneously). Some of the newest generation ‘load and go’ molecular analyzers are detailed below.

VERIS Mdx Molecular Diagnostics System
The DxN VERIS combines sample prep and sample analysis steps into a single workflow. The automation of DNA extraction, purification, assay set-up and analysis saves the user time and also prevents user error and the risk of contamination. Using real-time PCR, the system is designed for multiplex assays and uses magnetic particle separation for nucleic acid extraction and purification. The initial test menu includes Cytomegalovirus, Hepatitis B, Hepatitis C and HIV-1 ......


Microbiology has traditionally involved use of blood cultures, however molecular methods are
increasingly employed in modern laboratories;
Beckman Coulter's VERIS Mdx Molecular Diagnostics System
Source: SelectScience
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