Why a mother's immune system doesn’t reject the fetus

Researchers at NYU School of Medicine have made an important discovery that partially answers the long-standing question of why a mother’s immune system does not reject a developing fetus as foreign tissue.

“Our manuscript addresses a fundamental question in the fields of transplantation immunology and reproductive biology, namely, how do the fetus and placenta, which express antigens that are disparate from the mother, avoid being rejected by the maternal immune system during pregnancy?” explained lead investigator Adrian Erlebacher, MD, PhD, associate professor of pathology and a member of the NYU Cancer Institute at NYU Langone Medical Center. “What we found was completely unexpected at every level.”

The researchers discovered that embryo implantation sets off a process that ultimately turns off a key pathway required for the immune system to attack foreign bodies. As a result, immune cells are never recruited to the site of implantation and therefore cannot harm the developing fetus.

The study, funded by grants from the National Institutes of Health and the American Cancer Society, appears in the June 8 issue of Science.

A central feature of the body’s natural immune defense against transplanted foreign tissues and pathogens is the production of chemokines as a result of the local inflammatory response.

The chemokines recruit various kinds of immune cells, including activated T cells, which accumulate and attack the tissue or pathogen. The chemokine-mediated recruitment of activated T cells to sites of inflammation is an integral part of the immune response.

During pregnancy however, the foreign antigens of the developing fetus and the placenta come into direct contact with cells of the maternal immune system, but fail to evoke the typical tissue rejection response seen with organ transplants.

Several years ago, Erlebacher and his research team found that T cells, poised to attack the fetus as a foreign body, were somehow unable to perform their intended role.

The finding prompted the researchers to wonder if perhaps there was some sort of barrier preventing the T cells from reaching the fetus.

They turned their attention to studying the properties of the decidua, the specialized structure that encases the fetus and placenta, and there, in a mouse model, they found new answers.

The research team has discovered that the onset of pregnancy causes the genes that are responsible for recruiting immune cells to sites of inflammation to be turned off within the decidua. As a result of these changes, T cells are not able to accumulate inside the decidua and therefore do not attack the fetus and placenta.

Specifically, they revealed that the implantation of an embryo changes the packaging of certain chemokine genes in the nuclei of the developing decidua’s stromal cells.

The change in the DNA packaging permanently deactivates, or “silences,” the chemokine genes.

Consequently, the chemokines are not expressed and T cells are not recruited to the site of embryo implantation.

Also of note, the observed change in the DNA packaging was a so-called ‘epigenetic’ modification, meaning a modification that changes gene expression without the presence of a hereditable gene mutation.

“These findings give insight into mechanisms of fetal-maternal immune tolerance, as well as reveal the epigenetic modification of chemokine genes within tissue stromal cells as a modality for limiting the trafficking of activated T cells,” Dr. Erlebacher said.

“It turns out that the cells that typically secrete the chemoattractants to bring the T cells to sites of inflammation are inhibited from doing so in the context of the pregnant uterus. The decidua appears instead as a zone of relative immunological inactivity.”

Inappropriate regulation of this process, Dr. Erlebacher explained, could cause inflammation and the accumulation of immune cells at the maternal-fetal interface, which could lead to complications of human pregnancy, including preterm labor, spontaneous abortion and preeclampsia.

Erlebacher and his team will next look to see if these epigenetic modifications are also present within the human decidua, and whether the failure to generate them appropriately is associated with complications of human pregnancy.

He explained that the study’s findings also raise the possibility that the same kind of mechanism could enhance a tumor’s ability to survive inside its host. The findings could have implications for autoimmune diseases, organ transplantation and cancer, as well as pregnancy.

“This is a very exciting finding for us because it gives a satisfying explanation for why the fetus isn’t rejected during pregnancy, which is a fundamental question for the medical community with clear implications for human pregnancy,” Dr. Erlebacher said.

“It also reveals a new modality for controlling T cell trafficking in peripheral tissues that could provide insight into a myriad of other conditions and diseases.”

Toxoplasma Gondii: How your cat could be making you ‘crazy’

It’s long been known that a microbe found in cat's can harm people with weakened immune systems, such as people with AIDS.

It’s also been known that pregnant women should avoid cat litter so they don’t catch the microbe, lest they pass it on to their babies, causing brain damage in the infants or even death.

The microbe in question is Toxoplasma gondii (T. gondii or Toxo for short).

New research from an unconventional scientist is showing that in certain circumstances, the microbe can alter our basic personalities, making us more or less outgoing, trusting and fearful, and even making us more prone to schizophrenia, car crashes and suicides.

The circumstances that create this possibility are as follows;

• We have to be infected by the microbe
• Our bodies will eventually overcome it, 
• But the parasite can lay dormant,
• and the danger lies in whether it lodges or travels to our brain cells

The researcher, the Czech evolutionary biologist Jaroslav Flegr, claims that when you consider all its impacts, “Toxoplasma might even kill as many people as malaria, or at least a million people a year.”

Read more of this article here: How your cat could be making you ‘crazy’

Can Playing Maternal Voice and Heartbeat Sounds Benefit Premies?

Nearly five years ago, Amir Lahav became a parent of twins born prematurely at 25 weeks. They weighed just over 1 pound each.

Welcoming two newborns into the family certainly changed his life, but as a neuroscientist, it also ended up changing the course of his research.

Lahav studies how the brain processes sounds, and worked primarily with neurologically impaired adults, but with the birth of his twins, his paternal instinct kicked in.

He approached the chief of newborn medicine at Brigham and Women’s Hospital in Boston, where the babies lay in incubators.

“Could I put a recording of my wife's voice in there?” Lahav asked, convinced that hearing their mother’s soothing tones would improve the babies’ development. The answer: It's certainly worthwhile.

Using his computer, Lahav recorded his wife’s voice telling the babies they’re fighters and urging them to be strong.

He also included some soothing piano music, figuring it could prove relaxing for preemies. Then he tinkered with the sound to make it resemble what a baby would hear in utero.

While we hear through air, babies in the womb process sound through fluid so what passes as hearing consists of more low-frequency vibrations. (Think about slipping beneath the surface of the bath as someone talks to you, or try speaking while putting a finger in each ear.) “It’s as if babies are living in a micro-subwoofer,” explains Lahav.

The twins seemed to like the recordings, and doctors and nurses in the neonatal intensive care unit (NICU) were intrigued.

Moreover, it proved therapeutic for Lahav and his wife. “It was not a controlled trial,” says Lahav, “but just a crazy father trying to do something because especially in the case of premature babies, you feel very helpless.”

Once his twins left the hospital, Lahav returned to thank the chief for letting him experiment.

One thing led to another, and they found themselves in a serious conversation about prematurity and how the focus of neonatal medicine has changed from saving the lives of these babies, doctors have grown expert at keeping preemies alive, to helping them grow into healthy children.

Studies have shown that premature infants are at greater risk of having low IQ and developing metabolic or chronic conditions in young adulthood that can shorten their lives.

Could keeping them bathed in mom’s comforting sounds lower the incidence of some of these adverse effects on their health? Lahav wound up with a job offer to find out.

Read more: Can Playing Maternal Voice and Heartbeat Sounds Benefit Premies?

Malaria treatment: Impact on disease risk for babies

The UK NHS Information Video is very good at explaining Malaria infections and preventative actions you can take, but it does not go into details of how it affects young women, pregnant women and young breast-feeding mothers.

Recent research has indicated that Mothers who receive treatment for malaria infection could pass on lower levels of natural immunity to their babies.

Edinburgh University experts found mice treated with malaria infection drugs before they became pregnant passed on fewer antibodies to their young.

Full-blown malaria gives the immune system the chance to produce protective antibodies to pass on.

However, it is thought the drug treatment shortens the process.

The mothers benefit while children's immunity is decreased, putting them at greater risk.

The researchers said their results highlighted the need to look at how treatment might be tailored most effectively for women and their babies.

Malaria affects millions of people worldwide, mainly in developing countries. One child dies from the disease in Africa every minute.

Dr Vincent Staszewski, of Edinburgh University's school of biological sciences, said: "How an infection plays out in an individual can impact on the immunity of the next generation.

"Some treatments against disease before or during pregnancy might be beneficial for maternal health but impair infant survival."

The study, published in Proceedings of the Royal Society B, was funded by the Wellcome Trust and the Royal Society.

China Institute for the Examination of Foetal Remains

A visitor looks at foetus specimens at the "Mysterious Life" museum of Dalian Hoffen Bio-Technique in Dalian, Liaoning province.

Founded by Dr Sui Hongjin in 2004, the company produces, preserves and exhibits plastinated biotic specimens of human and animals.

The specimens, including whole bodies as well as individual organs and transparent body slices, have been meticulously dissected and preserved to allow visitors to view muscular, nervous, circulatory, respiratory and digestive systems. According to Sui, the bodies are legally collected from medical universities.

Picture: REUTERS/Sheng Li

Growing brain is particularly flexible

The brain is continuously changing. Neuronal structures are not hard-wired, but are modified with every learning step and every experience. Certain areas of the brain of a newborn baby are particularly flexible, however.

In animal experiments, the development of the visual cortex can be strongly influenced in the first months of life, for example, by different visual stimuli.

Nerve cells in the visual cortex of fully-grown animals divide up the processing of information from the eyes: Some “see” only the left eye, others only the right. Cells of right or left specialisation each lie close to one another in small groups, called columns.

The researchers showed that during growth, these structures are not simply inflated — columns do not become larger but their number increases. Neither do new columns form from new nerve cells. The number of nerve cells remains almost unchanged, a large part of the growth of the visual cortex can be attributed to an increase in the number of non-neuronal cells.

These changes can be explained by the fact that existing cells change their preference for the right or the left eye. In addition, another of the researchers’ observations also points to such a restructuring: The arrangement of the columns changes. While the pattern initially looks stripy, these stripes dissolve in time and the pattern becomes more irregular.

“This is an enormous achievement by the brain — undertaking such a restructuring while continuing to function,” says Wolfgang Keil, scientist at the Max Planck Institute for Dynamics and Self-Organization Göttingen and first author of the study.

“There is no engineer behind this conducting the planning, the process must generate itself.” The researchers used mathematical models and computer simulations to investigate how the brain could proceed to achieve this restructuring.

On the one hand, the brain tries to keep the neighbourhood relations in the visual cortex as uniform as possible. On the other, the development of the visual cortex is determined by the visual process itself — cells which have once been stimulated more strongly by the left or right eye try to maintain this particular calling.

The researchers’ model explains the formation of columns by taking both these tendencies into account. The scientists showed that when the tissue grows and the size of the columns is kept constant, the columns in the computer model change exactly as they had observed in their experimental studies on the visual cortex of the cat: The stripes dissolve into a zigzag pattern and thus become more irregular. In this way, the researchers provide a mathematical basis which realistically describes how the visual cortex could restructure during the growth phase.