Cell and DNA

Can Genetics affect how well we accept Transplants?

What are the different types of transplant?

When most people think of transplantation, they are usually thinking of a ‘solid’ organ transplant.  This is the process of taking a working organ from someone who can either survive without it or who has died recently (but their organs are fine) and putting it inside someone else who needs it. Liver, kidney and heart transplants are examples of these.

Another transplant type that is talked about less often is the transplantation of bone marrow. You may have heard of stem cell transplants (there are several types). A bone marrow transplant is a type of stem cell transplant. This is because the marrow contains the cells that make up your blood and immune system. The medical community calls this type of transplant a ‘Haematopoietic Stem Cell Transplant’ or HSCT. Haematopoietic means ‘the forming of blood cells’.

Who needs a HSCT?

Most people who need a bone marrow transplant have either got a problem with their immune system or their red blood cells. Often people with leukaemia (too many white blood cells that often don’t work properly) need to have their bone marrow replaced so they can produce normal white blood cells. Other reasons for needing a HSCT could be due to a condition called aplastic anaemia (where your bone marrow doesn’t make new blood cells) or sickle cell anaemia (where the red blood cells that are produced are misshapen). There are many more reasons for needing a HSCT and it has become a very important procedure.

What are the common complications of HSCT?

A HSCT is a very advanced procedure that can have a lot of complications. The main reason it’s so difficult to replace bone marrow is due to the immune system. Before you can insert the new bone marrow stem cells, you have to make sure that all the old bone marrow has been removed. The reason for needing to do this is because the new immune system from the transplant can start to attack your body. This causes a condition known as graft vs host disease (GVHD) where essentially the new immune system can’t tell the difference between your body’s cells and infectious pathogens like bacteria and viruses. This is different from a transplant rejection which is the opposite (your body rejects the new immune system).

One of the most dangerous periods of a HSCT is when the old bone marrow has just been removed and the new bone marrow hasn’t been put in yet or started to develop the white blood cells needed to fight pathogens. At this point, you don’t have an immune system and a common cold could kill you. This is why doctors put these patients in a ‘clean room’, where there is a much lower risk of infection.

What role do genetics play in our immune system?

The reason we all look different to each other and family members can look similar is due to our genetic profiles. Our DNA has coding parts and non-coding parts. It’s the coding parts that we see, for instance the gene that codes for blue eyes or brown. However, the biggest and most frequent genetic differences between humans isn’t actually in the coding part of our DNA, it’s in the part that scientists used to call ‘junk DNA’ – the non-coding part.

Recently, the medical community is realising that junk DNA isn’t really as useless as previously thought and often evolves into functional coding DNA. Scientists believe that non-coding DNA has a purpose as we have kept it in our genome throughout evolution.

Recent discoveries have shown us how our different genetic makeup can affect our immune systems. Some people may have better genes to fight off infections but also have an overactive immune system that can make transplant rejection occur more frequently.

To make matters even more complicated, scientists have found a link between the bacteria in our gut and our genes. We all have different levels of bacteria in our digestive systems. Most of this is helpful bacteria that can help us digest food easier and even provide us with more nutrients. ‘Good bacteria’ is often referred to as mutualistic as we help it and it helps us. We also have ‘commensal’ bacteria is our digestive system that don’t hurt us or help us. Having said that, commensal bacteria can become dangerous if the delicate level of bacterial balance is disturbed.

One of the first drugs given to transplant patients are antibiotics. As we mentioned earlier, getting an infection with no immune system is life threatening and so doctors give these patients antibiotics just in case. The problem with this is that it can kill all bacteria (both good, commensal and bad), which causes the bacterial balance of your gut to go wrong. Ironically, sometimes getting rid of the good bacteria can make way for bad bacteria (if they are more antibiotic resistant) as there’s less competition. Studies have shown that bacteria that take this opportunity (also known as opportunistic infections) can cause GVHD, infections and organ failure.

The balance of your gut’s bacteria is mostly determined by your environment, but recently it’s been discovered that your genetics can also play a role in the bacterial balance. Your immune system (which genes play a major role in) can control how many nutrients are available and the secretion of certain antibodies (see this article on antibodies), which in turn affects the chemical and physical makeup of the bacteria in your digestive system.

Even more shockingly, pathogenic or ‘bad’ bacteria can also play a role in what proteins your body expresses and can attempt to change cell pathways to allow themselves to spread leading to a bigger infection. Recent discoveries have shown that even commensal bacteria can do this. This is why the correct balance of bacteria in the gut is so important to lower the risk of GVHD.

A diagram showing how bone marrow transplants can affect the bacteria in your digestive system. Dysbiosis is another word for the wrong levels of bacteria.

So what does this all mean?

For patients that need a bone marrow transplant, more focus needs to be made on the gut, as this may play an important role on how well they accept the new transplant.

This article tells us that, with this new information, we should consider treatments that help our gut bacteria stay balanced. These can include probiotics, diet changes, bioengineered bacteria, more precise antibiotics or a faecal transplant (yes poop contains a lot of good bacteria too!). With the introduction of artificial intelligence, techniques could be developed where clinical information and bacterial balances are compared with each other to come up with a strategy for addressing infections in HSCT patients.

 

Reference: https://www.frontiersin.org/articles/10.3389/fmicb.2018.02317/full

Journal: Frontiers in Microbiology, Volume 9, Article 2317, 02 October 2018

Authors: J. Luis Espinoza, Yohei Wadasaki and Akiyoshi Takami

Copyright: Open Access

 

 

 

Bacteria

Could the Bacteria in your stomach cause Parkinson’s disease?

What is Parkinson’s disease and how does it affect you?

Parkinson’s disease is the second most common neurodegenerative condition (which means the destruction of nerve and brain cells) in the world. It causes your body to shake (the medical community call this tremors) and bradykinesia (which means slow movement). Doctors looking at movement call this ‘motor function’. Parkinson’s affects the brain by decreasing the amount of Dopamine available. Dopamine is one of the chemicals that your brain needs for its cells to communicate with each other. Cells that produce dopamine die in those with Parkinson’s disease. Another problem that Parkinson’s disease can cause, it the creation of ‘Lewy bodies’. These are abnormal protein deposits that can block cells in the brain from communicating with each other

A neuron located in the brain. Parkinson’s Disease can cause Lewy Bodies to deposit in these cells – these are shown in red

 

The cause of Parkinson’s is thought to be genetic based, however in reality, most cases are caused by something in our environment. The environmental cause of Parkinson’s has been hard to locate, however research has shown that it more than likely begins in the stomach.
Often an early symptom of Parkinson’s begins with stomach issues like over salivating, constipation, feeling sick and incontinence which then develops into motor issues causing problems with walking and tremors.
This study looked into a specific type of pathogenic bacteria called Helicobacter Pylori. This bacteria has chronically infected half of the world population and can lead to stomach ulcers and cancer.

How could H. Pylori cause Parkinson’s disease?

This authors in this study came up with 4 possible ideas for how H. Pylori could cause Parkinson’s:

  1. Toxins produced by the bacteria
  2. Disturbing the delicate balance of bacteria in your gut
  3. Inflammation in the gut that crosses into the brain (via the gut-brain axis – as your brain can influence your gut and your gut can influence your brain)
  4. Manipulation of how drugs move around your body. H. Pylori could affect how Levodopa (a chemical that can be turned into Dopamine) is absorbed by the body

What did they discover?

The key findings were:

  1. People who have Parkinson’s disease are 1.5 to 3 times more likely to be infected with H. Pylori than those who don’t have the disease
  2. Parkinson’s patients who are infected with H. Pylori are show worse motor functions than those who aren’t infected
  3. Removing H. Pylori from infected Parkinson’s patients improved their motor function over those who didn’t get their H. Pylori removed
  4. Removing H. Pylori improved Levodopa absorption in Parkinson’s patients compared to those who didn’t have it removed

This article has shown that there is clearly a link between your stomach and Parkinson’s disease, particularly if you are infected with the stomach dwelling H. Pylori bacteria. The mechanisms that these bacteria take to cause or contribute to Parkinson’s disease is still unclear and more research needs to be done focusing on the H. Pylori toxins, inflammation, Levodopa absorption and the carefully regulated bacterial balance in your gut.

 

Reference: https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd181327

Journal: Journal of Parkinson’s Disease, Volume 8, Issue 3, 14 May 2018

Author: David J. McGeea, Xiao-Hong Lub and Elizabeth A. Disbrowb

Copyright: Open Access

Pollution

Air pollution’s effect on our blood vessels

Is air pollution that bad? Are cardiovascular diseases a big problem?

It’s long been known that air pollution contributes to global warming and can affect our lungs. This article shows us that air pollution may go one step further and actually affect our cardiovascular system too!

 

The first graph (A) shows the risk factors for diseases leading to death around the world between 1990 and 2015. You can see that high blood pressure is still the biggest risk factor for death around the globe. The second graph (B) shows the number of deaths due to PM2.5. PM2.5 is basically a complicated way of saying very very small particles (smaller than dust or pollen) – take a look at the picture below. Some definitions for graph A: Tracheal and Bronchial refer to the breathing tubes of the lungs (dark blue), Ischaemic means a restriction of blood flow causing less oxygen to be able to get where it’s supposed to go (light blue), Cerebrovascular refers to the blood vessels of the brain (red), Chronic Obstructive Pulmonary Disease, also known as COPD refers to a group of lung conditions that cause trouble breathing (purple) and lower respiratory tract infections are lung infections like Pneumonia (green).

So what we can see here is that clearly deaths due to an increase in PM2.5 pollution are increasing. PM2.5 particles are particularly bad as they can penetrate deep into your lungs when you breathe them in as they’re so small.

 

 

What has air pollution got to do with our blood vessels?

This study looked into endothelial cells (or the endothelium part of a blood vessel). These are a thin layer of cells on the inside of our blood vessels that have direct contact with our blood. Whilst pollution has been shown to affect our cardiovascular system in many different ways, one of the critical steps that leads to the risk factors described above are changes to the endothelium. These cells are involved in the constriction or relaxation of our blood vessels (scientists call this vascular tone). They are also important in injury repair.

 

How do our endothelial cells go wrong?

So now we know that air pollution containing very small particles of pollutants (carbon monoxide, nitrogen dioxide and many others) are increasing the number of PM2.5 related deaths – how does it actually affect our cardiovascular system?

One of the main causes of damage to our blood vessels is through a process called oxidative stress. This process happens when reactive oxygen species are present in our lungs and blood stream. These are highly reactive chemicals (they are also found in bleach and in our own immune system to kill pathogens). These reactive chemicals can damage our blood vessels and mutate our DNA.

This article explains that we have evidence of air pollution causing the production of reactive oxygen species in in vitro cell culture (testing cells in the lab), animal and human studies. Animal studies have also shown that if you remove the mechanism that causes reactive oxygen species (in this case pollution), endothelial and blood vessel health starts to get better. Other studies showed that certain air pollutants can get into the central nervous system (the brain and spinal cord) and affect your blood pressure and metabolism. Our body’s immune system can also become affected as it attempts to clear the pollutants and reactive oxygen species from our body, meaning less availability to fight off infections.

What does this all mean?

Whilst it is widely known that pollution affects our lungs and contributes to global warming, this article has shown that pollution could also affect our blood vessels, metabolism, blood pressure and immune system. This article argues that with the increasing population and life expectancy causing an increase in energy and transportation requirements, more research should be done to protect millions of at risk people from cardiovascular diseases caused by pollution. Pollution’s direct influence on global warming will also have an impact on health as temperatures rise and carbon dioxide levels increase.

 

Reference: https://academic.oup.com/eurheartj/article/39/38/3543/5074161

Journal: European Heart Journal, Volume 39, Issue 38

Authors: Thomas Münzel, Tommaso Gori, Sadeer Al-Kindi, John Deanfield, Jos Lelieveld, Andreas Daiber and Sanjay Rajagopalan

Copyright: Open Access

 

Female Male symbols

Sex Hormones and their effect on your immune system

What is a hormone?

A hormone is a chemical produced by the body that can control and regulate the activity of certain cells or organs. An example of a non-sex specific hormone is vasopressin. This hormone is released by the pituitary gland (which is found on the underside of your brain) when we are dehydrated in order to preserve water. This hormone travels in the blood from your head to your kidneys where it acts on kidney cells to instruct them to hold onto more water.

What are sex hormones?

Sex hormones are chemicals that tend to affect sexual development and reproduction. Most people think that men produce testosterone and women produce oestrogen and progesterone. However, both sexes actually produce all 3, but in varying amounts.

Oestrogen (or Estrogen) is typically associated with women and Testosterone with men, although both sexes have both hormones.

 

Do sex hormones affect our immune systems?

Studies that go back as early as the 1940’s have shown that women tend to have better immune systems as they are better at producing antibodies. This can actually work against them as there may be a greater chance that their immune system could become overactive and start to attack healthy cells instead of the pathogens in our blood (this is called autoimmunity). If you want to know more about what an antibody is, what a pathogen is and some more information on autoimmunity, take a look at this article.

The difference between men and women’s immune responses can be directly related to the sex hormones that each gender has. This article suggests that sex hormones have an impact on the amount and type of bacteria found in the body.

How do these sex hormones affect our immune systems?

Testosterone (which is generally higher in men) has been shown to lower your immune system (also known as immunosuppression). Oestrogen on the other hand, has been shown to boost your immune system (also known as immunoenhancing).

A model of these immune system differences were put to test in mice. Scientists tested the amount of inflammation in male mice by injecting them with oestrogen and decreasing their testosterone through castration (removal of the testicles). They discovered that these mice were at greater risk of developing autoimmunity, much like what is seen in autoimmune women.

As mentioned earlier, women have a more active immune system and are more at risk of autoimmune disorders like rheumatoid arthritis or lupus. Whilst men, (who have a less active immune system) are more at risk of developing cancer as they cannot get rid of faulty cells as quickly as women can.

Why do men and women have different immune systems?

One of the reasons men and women may have different immune systems could be due to the evolution and preservation of humankind. In order for women to reproduce, it makes sense for their immune systems to be stronger so that they are healthy enough to have children.

What does this research mean for the future?

Currently there are no disease treatments that are based on the sex of a patient (unless specific to their reproductive organs). This research has highlighted that more research should be undertaken on the role of sex-specific immune responses, as one day we may be able to treat men and women differently to match their immune systems.

 

Reference: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01931/full

Journal: Frontiers in Immunology, Volume 9, August 2018

Author: Veena Taneja

Copyright: Open Access

Antibodies

Autoimmune Diseases – when our body attacks itself

How does immunity work?

When we feel ill, our body is usually fighting off germs (the medical community call them pathogens). Our body does this in many different ways. Our immune system is mostly made up of white blood cells. These cells can kill pathogens by eating them, injecting them with materials that kill them or by tagging them with antibodies. These antibodies act like little flags that notify the other white blood cells that there is a pathogen in the blood and essentially marks them as targets.

What is autoimmunity?

These antibodies are great for letting other white blood cells know where the dangers are in the body, but sometimes our antibodies can get confused and end up tagging normal parts of our own body! This is how type 1 diabetes occurs. Our cells start to attack the pancreas until it doesn’t work anymore causing our blood sugar to become unregulated. When our antibodies start to attack our own body, we call them auto-antibodies. Autoimmunity is currently treated by reducing our immune system’s strength (immunosuppressant therapy).

Whilst we know what happens during autoimmunity, we largely don’t know what causes our antibodies to turn against us. Having said that, recent research has given us a clue as to what might be causing some autoimmune diseases.

Macrophage – a white blood cell that ‘eats’ pathogens

What are commensal microbes?

Commensal microbes are essentially the ‘good’ bacteria that you find in yogurts and health drinks. These help you with digestion and can actually boost your immune system.

So what was discovered?

Blood was taken from people who have a known autoimmune disease and their antibodies were tested. It was found that these patients had antibodies that were programmed to target the good commensal bacteria. It was also found that the antibodies that attacked the good bacteria also cross reacted with human tissue and then ended up attacking healthy cells.

What does this mean/where to from here?

This research has shown that one of the causes of autoimmune diseases may be due to a bad relationship between certain people’s immune system and the ‘good’ bacteria. Getting rid of the specific type of ‘good’ bacteria that causes the body to make autoantibodies may be a new type of therapy to consider for some autoimmune diseases.

 

Reference: https://www.frontiersin.org/articles/10.3389/fmed.2018.00153/full

Journal: Frontiers in Medicine, Volume 5,  May 2018

Authors: Peilin Zhang, Lawrence M. Minardi,  J. Todd Kuenstner, Steven M. Zekan and Rusty Kruzelock

Copyright: Open Access