Your Body's Defense Against COVID-19

Why do some people get seriously ill from COVID-19 and others show slight or no symptoms? The simple answer is that right now scientists and disease experts aren’t exactly sure, but one fact seems clear: The health of your immune system is a substantial factor in how each person reacts to a COVID-19 viral infection.

With that fact in mind, let’s examine several recent and new studies about the immune system.

In a new study, researchers for the first time have found individual cells that cause autoimmune disease from patient samples. They also uncovered how these cells ‘go rogue’ by evading checkpoints that normally stop immune cells from targeting the body’s own tissues.

The findings could have big implications for the diagnosis and treatment of autoimmune disease. The research was led by researchers at the Garvan Institute of Medical Research.

There are more than 100 different autoimmune diseases.

A recent study by Johns Hopkins Medicine researchers has demonstrated that in mice -- and probably humans as well -- one biological mechanism may play a key role in protection from such attacks, known as autoimmune responses, which are a hallmark of diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes.

The researchers detailed their study in a paper published in late February in the journal PLOS Biology.

"Short protein fragments, known as peptides, that come from bacteria, viruses and other pathogens act as antigens to trigger our immune system to remove the invaders, a process that depends on other proteins acting and interacting in a specific sequence of events," says Scheherazade Sadegh-Nasseri, Ph.D., professor of pathology at the Johns Hopkins University School of Medicine and senior author of the paper. "In our mouse study, we have shown that a specific disruption in this regimen can redirect the immune system to turn against a healthy body -- something that we believe also is likely occurring in humans."

In their effort to identify this disruption, the researchers relied on the fact that for a mammal's immune system to trigger a response, antigenic peptides must be exposed, or "presented," to immune cells known as T lymphocytes, or T cells. This is achieved when the protein fragments attach to a molecule called major histocompatibility complex II, or MHC II, that sits on the surface of a white blood cell known as an antigen presenting cell, or APC.

Immature T cells are biologically attracted to these presented antigens, which are called epitopes. If the T cell has a receptor on its surface with a shape that conforms to the antigen -- akin to fitting a key into a lock -- it latches on and triggers the T cell's maturation into what is called a helper T cell (also known as a CD4 T cell).

These cells then kick the immune response into high gear, helping to fight the internal war against foreign invaders by activating other immunity soldiers -- B cells, macrophages and "killer" T cells -- to secrete antibodies, digest and destroy microbes, and remove infected cells, respectively.

Once activated, the immune system remembers the antigen for a faster response to future attacks by the same infectious agent.

The immune system and Parkinson’s

A new study co-led by scientists at the La Jolla Institute for Immunology (LJI) adds increasing evidence that Parkinson's disease is partly an autoimmune disease. In fact, the researchers report that signs of autoimmunity can appear in Parkinson's disease patients years before their official diagnosis.

The research could make it possible to someday detect Parkinson's disease before the onset of debilitating motor symptoms -- and potentially intervene with therapies to slow the disease progression.

The study, published in the April issue of Nature Communications, was co-led by LJI professor Alessandro Sette, Dr. Biol. Sci, and Professor David Sulzer, Ph.D., of the Columbia University Medical Center.

Scientists have long known that clumps of a damaged protein called alpha-synuclein build up in the dopamine-producing brain cells of patients with Parkinson's disease. These clumps eventually lead to cell death, causing motor symptoms and cognitive decline.

"Once these cells are gone, they're gone. So if you are able to diagnose the disease as early as possible, it could make a huge difference," says LJI research assistant professor Cecilia Lindestam Arlehamn, Ph.D., who served as first author of the new study.

A 2017 study led by Sette and Sulzer was the first to show that alpha-synuclein can act as a beacon for certain T cells, causing them to mistakenly attack brain cells and potentially contribute to the progression of Parkinson's. This was the first direct evidence that autoimmunity could play a role in Parkinson's disease.

The new findings shed light on the timeline of T cell reactivity and disease progression. The researchers looked at blood samples from a large group of Parkinson's disease patients and compared their T cells to a healthy, age-matched control group. They found that the T cells that react to alpha-synuclein are most abundant when patients are first diagnosed with the disease. These T cells tend to disappear as the disease progresses, and few patients still have them ten years after diagnosis.

The researchers also did an in-depth analysis of one Parkinson's disease patient who happened to have blood samples preserved going back long before his diagnosis. This case study showed that the patient had a strong T cell response to alpha-synuclein ten years before he was diagnosed with Parkinson's disease. Again, these T cells faded away in the years following diagnosis.

"This tells us that detection of T cell responses could help in the diagnosis of people at risk or in early stages of disease development, when many of the symptoms have not been detected yet," says Sette. "Importantly, we could dream of a scenario where early interference with T cell responses could prevent the disease from manifesting itself or progressing."

Exercise and the immune system

Being in isolation without access to gyms and sports clubs should not mean people stop exercising, according to a new study from researchers at the University of Bath. Keeping up regular, daily exercise at a time when much of the world is going into isolation will play an important role in helping to maintain a healthy immune system.

The analysis, published in the international journal Exercise Immunology Review, involving leading physiologists Dr James Turner and Dr John Campbell from the University of Bath's Department for Health, considers the effect of exercise on our immune function.

Over the last four decades, many studies have investigated how exercise affects the immune system. It is widely agreed that regular moderate intensity exercise is beneficial for immunity, but a view held by some is that more arduous exercise can suppress immune function, leading to an 'open-window' of heightened infection risk in the hours and days following exercise.

In a benchmark study in 2018, this 'open window' hypothesis was challenged by Dr Campbell and Dr Turner. They reported in a review article that the theory was not well supported by scientific evidence, summarizing that there is limited reliable evidence that exercise suppresses immunity, concluding instead that exercise is beneficial for immune function.

They say that, in the short term, exercise can help the immune system find and deal with pathogens, and in the long term, regular exercise slows down changes that happen to the immune system with aging, therefore reducing the risk of infections.

In a new article, published this month, leading experts, including Dr Turner and Dr Campbell, debated whether the immune system can change in a negative or positive way after exercise, and whether or not athletes get more infections than the general population. The article concludes that infections are more likely to be linked to inadequate diet, psychological stress, insufficient sleep, travel and importantly, pathogen exposure at social gathering events like marathons -- rather than the act of exercising itself.

Author Dr James Turner from the Department for Health at the University of Bath explains: "Our work has concluded that there is very limited evidence for exercise directly increasing the risk of becoming infected with viruses. In the context of coronavirus and the conditions we find ourselves in today, the most important consideration is reducing your exposure from other people who may be carrying the virus. But people should not overlook the importance of staying fit, active and healthy during this period. Provided it is carried out in isolation -- away from others -- then regular, daily exercise will help better maintain the way the immune system works -- not suppress it."

Co-author, Dr John Campbell added: "People should not fear that their immune system will be suppressed by exercise placing them at increased risk of Coronavirus. Provided exercise is carried out according to latest government guidance on social distancing, regular exercise will have a tremendously positive effect on our health and wellbeing, both today and for the future."

Regular moderate intensity aerobic exercise, such as walking, running or cycling is recommended, with the aim of achieving 150 minutes per week. Longer, more vigorous exercise would not be harmful, but if capacity to exercise is restricted due to a health condition or disability, the message is to 'move more' and that 'something is better than nothing'. Resistance exercise has clear benefits for maintaining muscles, which also helps movement.

During the outbreak of COVID-19, the researchers underline the importance of maintaining good personal hygiene when exercising, including thoroughly washing hands following exercise. To give the body its best chance at fighting off infections, they suggest in addition to doing regular exercise, people need to pay attention to the amount of sleep they get and maintain a healthy diet, that is energy balanced to account for energy that is used during exercise.

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