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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Pre-Med and Key Requirements for a Medical School !

What is pre-med? When people say that they’re pre-med, what does that actually mean? If you’re planning to attend a med-school and become a doctor, it’s important that you understand the definition of pre-med and what you should be doing as a pre-med student.

Read on to learn what it really means to be a pre-med, what you should be focusing on to get into med school, and what the best majors for pre-meds are and why.

What Does Pre-Med Mean?

“Pre-med” is the term people use to show that they want to go to a med-school and are taking the classes they need to get there. It’s primarily used by college students. There isn’t actually a major called “pre-med;” pre-med is just a term to let people know you have plans to be a doctor. You can be a biology major and a pre-med, a Spanish major and a pre-med, etc.

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Know Blood Tests During Pregnancy !

Pregnancy Blood Tests:

As part of your antenatal care you’ll be offered several blood tests. Some are offered to all women, and some are only offered if you might be at risk of a particular infection or inherited condition.

All the tests are done to check for anything that may cause a problem during your pregnancy or after the birth, or to check that your baby is healthy, but you don’t have to have them if you don’t want to.

Talk to your midwife or doctor and give yourself enough time to make your decision. They should also give you written information about the tests. Below is an outline of all the tests that can be offered.

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Thyroid Hormone Transporters — Functions and Clinical Implications

Thyroid Hormone Transporters

Thyroid hormones regulate many metabolic and developmental processes, including key having functions in the brain, and mutations in a transporter specific for thyroid hormone leads to severe neurological impairment. This review article attempts to discuss the physiological importance and clinical implications of thyroid hormone transport, with a particular focus on brain development.

The thyroid hormones, T4 (3,5,3′,5′tetraiodo-L-thyronine) and T3 (3,5,3′tri-iodo-L-thyronine; also known as tri-iodothyronine) are iodinated amino acids produced and secreted by the thyroid gland. These hormones regulate many developmental and metabolic processes. The nuclear T3 receptors are ligand-modulated transcription factors encoded by two genes, THRA and THRB. These genes encode several receptor proteins, of which three (thyroid hormone receptor α1, thyroid hormone receptor β1 and thyroid hormone receptor β2) interact with T3, which results in tissue-specific and developmentally-dependent transcriptomic changes. In the developing cerebral cortex, 500–1,000 genes are directly or indirectly affected by thyroid hormones. In addition, both T4 and T3 perform nongenomic, extranuclear actions. For example, T3 might interact with a plasma-membrane-associated thyroid hormone receptor α variant, and with cytoplasmic thyroid hormone receptor β, while T4 interacts with integrin αvβ3 and activates diverse signalling pathways such as the phosphoinositide 3-kinase pathway and mitogen-activated protein kinase pathways.

Metabolism of thyroid hormones includes the processes of deiodination, deamination, decarboxylation, sulphation and glucuronidation, which have been extensively reviewed elsewhere. The most relevant pathway for the discussion in this Review is deiodination, a process that activates or inactivates thyroid hormones. Deiodinases are selenoproteins that catalyze the removal of specific iodine atoms from the phenolic or tyrosyl rings of the iodothyronine molecule. Type 1 iodothyronine deiodinase and type 2 iodothyronine deiodinase (DIO1 and DIO2, encoded by the DIO1 and DIO2 genes, respectively) have phenolic, or 'outer' ring, activity and convert T4 to T3. In extrathyroidal tissues, this pathway generates ∼80% of the total body pool of T3. Type 3 iodothyronine deiodinase (DIO3, encoded by the DIO3 gene) and DIO1 have tyrosyl, or 'inner' ring, activity and convert T4 and T3 to the inactive metabolites 3,3′5′-triiodo-L-thyronine (rT3) and 3,3′-diiodo-L-thyronine (T2), respectively; rT3 is then further metabolized by DIO1 to T2.

• Many proteins can mediate thyroid hormone transport, but only mutations in genes encoding MCT8, MCT10 and OATP1C1 have pathophysiological effects attributed to this process

• MCT8 mutations lead to Allan–Herndon–Dudley syndrome, which is characterized by truncal hypotonia and results in spastic quadriplegia, lack of speech, severe intellectual deficit and altered thyroid hormone concentrations

• MCT8 deficiency impairs the transfer of thyroid hormones across the blood–brain barrier

• Mct8-deficient mice lack neurological impairment possibly due to the presence of Oatp1c1, a T4 transporter, but levels of OATP1C1 in the primate blood–brain barrier are very low

• Histopathological studies of patients with mutations in MCT8 support the concept that defective thyroid hormone action in the brain during development leads to the neurological syndrome

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Serum Iron Test: High, Low, and Normal Ranges !

Serum Iron Test

Having too much or too little iron in the blood can cause serious health problems.

If a doctor suspects that a person does not have a healthy amount of iron in their blood, they may order a serum iron test.

In this article, learn more about the uses of a serum iron test. We also explain the normal ranges of iron in the blood and the treatment options for people whose iron levels are too high or too low.

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H2Oh! Water is actually two liquids disguised as one.

H2Oh!

Earth's most precious liquid is weird, and if it wasn't we would die. Now experiments have uncovered its secret: it's not one liquid, it's two

“WATER is very strange,” says Anders Nilsson. He should know: he has been studying the stuff for most of his working life. His claim may be hard for the rest of us to swallow – after all, what could be more ordinary than water? Its behaviour is so familiar, its appearance so commonplace, that we are tricked into assuming that it is more or less the same as everything else. But water is uniquely weird. If it weren’t, none of us would be here to notice.

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For example, if water weren’t densest at around 4°C rather than as ice, lakes and rivers would freeze from the bottom up, slowly killing their inhabitants. If it weren’t so spectacularly good at absorbing heat, the planet would have boiled over long ago. And if its molecules, barrelling through membranes or darting down veins, weren’t so good at sweeping other chemicals along, plants and animals would die of malnutrition.

Scientists have been plumbing the depths of water’s strangeness since at least the time of Galileo, to no avail. But now, thanks to the work of Nilsson and others, we might be on the verge of understanding why it behaves the way it does. Their explanation is as strange and wonderful as the stuff itself: water isn’t one liquid, but two.

On one level, it’s no surprise that water comes in multiple forms. It exists in three phases, as a solid, liquid or gas, depending on the temperature and pressure where you find it. At sea level, water turns to steam at 100°C, but at altitude, where the atmospheric pressure is reduced, you can get …

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What is a free PSA test and what is it for?

Free PSA Test

"The free prostate-specific antigen test, known as the free PSA test, is used to help detect signs of prostate cancer. The test measures the level of unbound prostate-specific antigen in the blood, which can help doctors to diagnose issues like inflammation of the prostate or cancer."

Free PSA tests are often used alongside other PSA tests to confirm a diagnosis or test results. Free PSA tests can also be used instead of a biopsy if the doctor suspects prostate cancer, but a biopsy may still be needed.

This article examines when a free PSA test is used, how it differs from a total PSA test, and what the results mean.

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Nipah Virus -Infection, Symptoms, Diagnosis & Treatment !

Viruses

Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis. Given the relatedness of NiV to Hendra virus, bat species were quickly singled out for investigation and flying foxes of the genus Pteropus were subsequently identified as the reservoir for NiV (Distribution Map).

In the 1999 outbreak, Nipah virus caused a relatively mild disease in pigs, but nearly 300 human cases with over 100 deaths were reported. In order to stop the outbreak, more than a million pigs were euthanized, causing tremendous trade loss for Malaysia. Since this outbreak, no subsequent cases (in neither swine nor human) have been reported in either Malaysia or Singapore.

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Microbes That Cause UTIs Use Hooks to Hold On While We Pee

Microbes

Urinary tract infections are typically caused by a bacterium that somehow manages to creep its way into the bladder, despite the intense pressures exerted by urination. It turns out these microbes use hooks to cling on in desperation while we pee.

As anyone who has ever had a UTI knows, such infections are supremely uncomfortable. They are caused by the intestinal bacterium Escherichia coli,which makes its way from from the urethra to the bladder. Nearly one in every two women will experience a UTI at some point during her life, but men can get them too (though less frequently).

Scientists have wondered how these microbes are capable of withstanding urinary flow, but new research from the University of Babel and ETH Zurich shows these tiny critters have evolved a rather clever trick in the form of built-in grappling hooks.

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