Molecular Basis of Tolerance and Immunity to Antigens.

Molecular Immunology

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.

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Heterogeneity in Tuberculosis.

Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), results in a range of clinical presentations in humans. Most infections manifest as a clinically asymptomatic, contained state that is termed latent TB infection (LTBI); a smaller subset of infected individuals present with symptomatic, active TB. Within these two seemingly binary states, there is a spectrum of host outcomes that have varying symptoms, microbiologies, immune responses and pathologies. Recently, it has become apparent that there is diversity of infection even within a single individual. A good understanding of the heterogeneity that is intrinsic to TB — at both the population level and the individual level — is crucial to inform the development of intervention strategies that account for and target the unique, complex and independent nature of the local host–pathogen interactions that occur in this infection. In this Review, we draw on model systems and human data to discuss multiple facets of TB biology and their relationship to the overall heterogeneity observed in the human disease.

Read more: Heterogeneity in Tuberculosis.

Figure 1: A classical tuberculosis granuloma. The hallmark tuberculosis
granuloma is a highly organized collection of immune cells that aggregate
around a central necrotic core.

Source: NATURE REVIEWS IMMUNOLOGY

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Can Vitamin D Really Stop You Getting Cold And Flu?

Have you had a cold, flu or even pneumonia in the last year? You're not alone - in fact you're among 70% of the UK population.

But a new study claims that three million people could be spared the sniffles if they took vitamin D pills.

That's more than the number of people who are stopped from getting the flu after having the vaccine.

The people behind the new study want vitamin D to be added to food so that everyone gets enough.

Read more: Can Vitamin D Really Stop You Getting Cold And Flu?

Source: bbc.co.uk/newsbeat

Boosting the Immune System to Effect Repairs and Fight Disease

Applications from Regenerative Medicine to Gene Therapy to Antiviral Therapeutics Emphasize Self-Healing

Therapeutic interventions of various kinds try to improve the body’s capacity to defend, repair, and even cure itself. Interventions that attempt to enhance self-healing span cell-based therapy, gene therapy, small molecule drugs, biologics, and tissue engineering.

Advances in each of these areas are being followed by Allied Market Research, which has concluded that stem cell technologies look especially promising. For example, stem cell technologies are set to revolutionize the human ability to produce neural cells in abundance.

Read more: Boosting the Immune System to Effect Repairs and Fight Disease

Source: genengnews

Take This Vitamin And You Will NEVER Get Another Bite From A Mosquito Again!

Ah… summer. Longer days, sunny skies, sandy beaches… and mosquitoes. Lots and lots of mosquitoes.

For some, this isn’t too big of a deal, as mosquito repellent has been on the market since 1956.

But, if you’re like me at all and you not only want to stop smelling like the burnt remains of a chemical plant after using repellent, but also are scared of the adverse effects of DEET in sprays and are more prone to getting bit (seriously though, mosquitoes seemed to love me and only me at parties), then taking Vitamin B1 could be your saving grace.

Vitamin B1 (also known as thiamine) is an essential vitamin your body needs. It can be found in foods such as yeast, oatmeal, brown rice, asparagus, kale, liver and eggs and is important in fighting stress and boosting immunity.

Read more: Take This Vitamin And You Will NEVER Get Another Bite From A Mosquito Again!

Source: SimpleCapacity

Breast-Feeding May Reduce Asthma Symptoms For At-Risk Infants

A new study provides further evidence of the health benefits of breast-feeding, after finding infants with a genetic susceptibility for asthma development are less likely to experience symptoms of the condition if they are breast-fed.

Asthma is estimated to affect around 8.6 percent of children and adolescents in the United States, making it one of the most common chronic childhood diseases.

Asthma symptoms are the same for children as for adults; these include wheezing, coughing, breathing problems, and chest tightness. However, because children have smaller airways, symptoms may be more severe.

As a result, asthma is the third leading cause of hospital stays and a leading cause of missed school days for children in the U.S.

While the precise causes of asthma remain unclear, studies have suggested the respiratory condition may arise as a result of environmental and genetic factors.

Read more: Breast-Feeding May Reduce Asthma Symptoms For At-Risk Infants

Breast-feeding may reduce respiratory symptoms for children genetically susceptible to asthma
development.

Source: medicalnewstoday

Liver Cancer Risk Influenced By Blood Selenium Levels

The risk of developing liver cancer may be significantly higher for people who have low levels of the nutrient selenium in their blood, suggests a new study published in the American Journal of Clinical Nutrition.

Selenium is a trace mineral present in soil, animal products, and plant-based foods, including seafood, Brazil nuts, organ meats, milk, and eggs.

The selenium content of food varies greatly, as it depends on how much of the element is in the plants animals consume, as well as how much is in the soil in which plants grow.

According to the National Institutes of Health (NIH), selenium is essential for human health, with beneficial roles for reproduction, the immune system, and DNA synthesis.

Studies have also shown that selenium has antioxidant properties, meaning it can protect against oxidative stress - the process by which uncharged molecules called free radicals damage cells.

Read more: Liver Cancer Risk Influenced By Blood Selenium Levels

Low blood selenium levels may put people at greater risk of liver cancer.

Source: medicalnewstoday

Immune cells self-healing brain after stroke

After a stroke, there is inflammation in the damaged part of the brain. Until now, the inflammation has been seen as a negative consequence that needs to be abolished as soon as possible. But, as it turns out, there are also some positive sides to the inflammation, and it can actually help the brain to self-repair.

"This is in total contrast to our previous beliefs", says Professor Zaal Kokaia from Lund University in Sweden.

Zaal Kokaia, together with Professor of Neurology Olle Lindvall, runs a research group at the Lund Stem Cell Center that, in collaboration with colleagues at the Weizmann Institute in Israel, is responsible for these findings. Hopefully, these new data will lead to new ways of treating stroke in the future. The study was recently published in the Journal of Neuroscience.

When stroke occurs, the nerve cells in the damaged area of the brain die, causing an inflammation that attracts cells from the immune system. Among them you find monocytes—a type of white blood cells produced in the bone marrow.

Read more: Immune cells self-healing brain after stroke

False-colored scanning electron micrograph of a blood clot. There are many red blood cells and

a single white blood cell held together in a meshwork of fibrin (brown).

Source: Anne Weston, LRI, CRUK, Wellcome Images

Disposing HIV from human immune cells with new gene-editing technique.

They've managed to shut down HIV replication permanently.

Using the much-touted CRISPR/Cas9 gene editing method, scientists have demonstrated how they can edit HIV out of human immune cell DNA, and in doing so, can prevent the reinfection of unedited cells too.

If you haven’t heard of the CRISPR/Cas9 gene-editing technique before, get ready to hear a whole lot more about it in 2016, because it’s set to revolutionise how we investigate and treat the root causes of genetic disease. It allows scientists to narrow in on a specific gene, and cut-and-paste parts of the DNA to change its function.

CRISPR/Cas9 is what researchers in the UK have recently gotten approval to use on human embryos so they can figure out how to improve IVF success rates and reduce miscarriages, and it’s what Chinese scientists were caught using in 2015to tweak human embryos on the down-low.

Earlier this year, scientists started using CRISPR/Cas9 to successfully treat a genetic disease - Duchenne muscular dystrophy - in living mammals for the first time, and now it’s showing real potential as a possible treatment for HIV in the future.

Read more: Disposing HIV from human immune cells with new gene-editing technique.

An HIV-infected T-cell.

Source: NIAID/Flickr

Mother's microbiome influence her offspring's immune system during gestation.

During gestation, a mother's microbiome shapes the immune system of her offspring, a new study in mice suggests. While it's known that a newborn's gut microbiota can affect its own immune system, the impact of a mother's microbiota on her offspring has largely been unexplored.

Here, Mercedes Gomez de Agüero et al. infected the guts of pregnant mice with E.coli engineered to dwindle over time, allowing the mothers to become germ-free again around the time they gave birth.

This temporary colonization of E.coli in the mother affected the immune system of her offspring; after birth, the offspring harbored more innate lymphoid and mononuclear cells in their intestines compared to mice born to microbe-free pregnant mothers. Similar results were seen when pregnant mothers were temporarily colonized with a cocktail of eight other microbes.

An RNA analysis of offspring born to gestation-only colonized mothers compared with controls revealed greater expression of numerous genes, including those that influence cell division and differentiation, mucus and ion channels, and metabolism and immune function.

By transferring serum from bacteria-colonized pregnant mice to non-colonized pregnant mice, the researchers found that maternal antibodies likely facilitate the transmission and retention of microbial molecules from a mother to her offspring.

Read more: Mother's microbiome influence her offspring's immune system during gestation.

Shaping of the immune system starts with the maternal microbiota.

Source: sciencedaily