A Conversation on Immunity

Over the last few decades, our knowledge surrounding human health and disease has advanced significantly, changing the landscape of modern medicine and our understanding of what it means to be “well”.

The COVID-19 pandemic forced daily routines to a sudden halt when numerous lockdowns were enforced around the globe. As humanity faced empty diaries and often solitude, opportunity arose to reflect on the habits and activities that typically occupy day-to-day life. Coupled with external narratives on the importance of keeping healthy to protect ourselves against the SARS-CoV-2 virus, for many, this experience prompted a new-found prioritization of “self-care” – finding new ways to look after our bodies and our minds.

The pandemic occurred at an interesting time for the healthcare system and medical establishment more generally. Global life expectancy has increased from 67.2 years in 2000 to 73.5 years in 2019, according to the latest report of the Global Burden of Diseases. While we may be living longer, human beings face ever-growing challenges such as the burden of chronic diseases and the mental health crisis. Consequently, modern medicine has started to shift focus from treating diseases as and when they occur, to disease prevention, or maintaining “wellness”.

Add the growing traction of the wellness industry – now estimated to be worth $4.5 trillion – into the equation and it’s arguable that, right now, humans have never been so invested in our health. Or perhaps more specifically, the tangible aspects of health – factors that we can aim to control to prevent disease.

A key component of staying healthy is the correct functioning of the immune system, the complex network of cellular processes and interactions that protect our bodies against foreign substances. Over recent decades, research published by scientists in the field of immunology has demonstrated direct links between dysregulation of the immune system and disease development. Excessive immune responses can result in conditions such as Crohn’s disease or asthma. Auto-immune diseases where the immune system fails to differentiate between foreign and “self” cells – such as rheumatoid arthritis – can majorly impact quality of life. The immune system is now even considered to be a major contributor in the pathology of Alzheimer’s disease, and some research has explored the impact of viral infections on the development of psychiatric symptoms.

There is an ever-growing amount of information shared daily on what we can do to maintain a healthy immune system. The source of such information varies, from academic journals, podcasts, blogs to social media. With the marketing of products claiming to “boost” or “hack” the immune system, it can be hard to cut through the noise and decipher what is backed by scientific evidence, and what is misinformation.

Dr. Jenna Macciochi is a lecturer in immunology at the University of Sussex, where her research centers on understanding the role that nutrition and lifestyle play in human immunity. In addition to her academic career, Dr. Macciochi is an established author. Her first book, Immunity: The Science of Staying Well was published in 2020, and her second book, Your Blueprint for Strong Immunity was published earlier this year. Collectively, Dr. Macciochi’s writing and academic research aims to “set the record straight” on the science underpinning human health and immunity, making this information accessible and actionable.

For this month’s feature article, Technology Networks sat down with Dr. Macciochi to ask: how can we really stay well? What has immunological research taught us about the effects of modern lifestyle on our bodies and what are some of the latest breakthroughs in this field?

Molly Campbell (MC): Why did you become so interested in immunology, and how did this evolve into your current research focus?   

Jenna Macciochi (JM): I was very interested in in health and disease as a child. I grew up on a farm, and my mum worked in food in catering, so there was always a big emphasis on how illness can be prevented at the dinner table. We cooked from scratch and grew a lot of our food ourselves. Living on a farm allows you see the circle of life, and I think I became very preoccupied as a child in understanding what made people stay well, and why some people got sick.

I went to the University of Glasgow, where I had wonderful lecturers who I found very inspiring, and the institute had a very small immunology program within the medical school, meaning you got to know your cohort very well. We had a great group of academics teaching us and I finally got some of the answers to the questions that I had about health and disease. From there, I was hooked.

I love how the immune system weaves into every aspect of our body in health and disease; it’s not just about protection against infection, or how to develop vaccines, but there are other components such as allergies, autoimmune diseases or cancer, the gut microbiome, etc.

In my 20s, I hit burnout for the first time. I realized that I had all this knowledge about the immune system and how to stay well, but I wasn’t applying it to my own life. That’s when I really started to follow my interests surrounding diet, lifestyle and the tangible things that we have at our fingertips to help us stay well. From there, I wanted to make the science accessible and actionable for us all, because I think there is a big disconnect between knowing what can make us well and applying it.

MC: Considering the landscape of human life and society now, why is immunology such an interesting research field to work in?

JM: Immunology branched off from an older line of science – microbiology. This is a research field that emerged when we first discovered microbes, tiny organisms that we can’t see but that can cause us to get sick. Prior to that, many sicknesses were attributed to miasma, or “bad air”; we didn’t have the tools to visualize microbes, so we couldn’t see them or analyze them. When those tools became available, we could finally see and study microbes. As a result, microbiology was founded.

Much later, we realized that some people were missing parts of their immune system, and as a result microbes could take over and make people sicker, or sick more often. That’s when the field started to discover white blood cells – our immune cells – and from there, immunology became its own discipline.

As a field, immunology is therefore relatively new. We’re discovering more and more, all the time – it evolves rapidly. In 2018, the Nobel Prize in Physiology and Medicine was awarded to James Allison and Tasuku Honjo for their discovery of cancer immunotherapy. Twenty years ago, the idea that the immune system could be involved in cancer, and the concept of weaponizing that same system to treat cancer, would not have been on anybody’s radar.

We now have data on the immune system going awry in patients with clinical depression, and other mental health problems. If we can go upstream and fix what's going on in their immune system, we can fix some of the depressive symptoms that they're experiencing. To me, that is mind blowing. There’s not a single condition documented that doesn't involve the immune system to some degree, which I think has so much potential for public health and the many disease risks that we are challenged with in today’s world.

MC: Could you pinpoint key breakthroughs that you think have helped the immunology research field flourish?

JM: The cancer immunotherapy breakthrough is incredible. In addition, the discovery of how we are all immunologically unique is fascinating – the genes that differ most between us are those attributed to different aspects of the immune system. Susumu Tonegawa won the 1987 Nobel Prize for his research exploring the genes that recombine in a unique way to make each of our individual antibodies and receptors for T cells. Even though we have a specific amount of DNA in our cells, we can make a limitless number of different antibodies and T cell receptors. Before, nobody could really figure out why that was. It is a finding that is especially relevant today when we look at how different individuals respond to SARS-CoV-2 infection. There is so much clinical variability, not just in COVID-19, but in other infectious diseases too.

The link between the immune system and mental health is another breakthrough in my opinion. Poor mental health is a growing problem, and the physical aspect of it is becoming increasingly clear. Bringing immunology and mental health research together is going to be extremely useful for tackling the growing challenges we face when treating mental health conditions.

We also can’t ignore the fact that vaccines are literally training our immune system against pathogens, and the developments that have occurred in this space. When the first vaccines were rolled out, we eradicated smallpox from the face of the planet. We are living among pathogens that might have killed our grandparents, or great grandparents, and we have a line of defence against them. Vaccines really have changed the face of public health. 

MC: Could you talk about the research methods that are adopted in immunology – how do we study the immune system?

JM: It is difficult to study the immune system, and this has hindered a lot of progress within the field. Our white blood cells aren’t just found in the blood; they exist all over the body, so if you take a blood sample from an individual, you’re not promised a holistic picture of what their entire immune system is doing. White blood cells are going to congregate at the body’s barriers – where we’re most likely to be exposed to pathogens or toxins – such as the oral cavity, the air ways, the digestive tract and underneath the skin. Of course, you can’t necessarily obtain biopsies from all of these different parts of the body to figure out what the immune system is doing in that specific location.

A lot of laboratories in immunology research will use animal model systems. This provides the opportunity to study a complete mammal and look at the immune system as a whole. But there are of course limits here too when you consider species differences, and the fact you still cannot obtain samples from specific locations of the body while studying the immune system in vivo.

MC: What can we do to help our immune system and improve our health more generally?

JM: That's something that we've all become quite cognizant of with the global pandemic situation. I love the phrase “the time to fix the roof is when the sun is shining”.  Many people will come to me when they’ve fallen ill and ask, “How do I get better?” The two main things your immune system requires are time and energy. It can take five days for your body to produce the highly specific antibodies that you need to fight against a pathogen. Resting allows your energy resources to be directed towards this process. Many people don't want to hear that. They want to know what vitamins and minerals they can take to get back on the road to recovery.

I think this can reflect the modern world. Time really is a big factor in any healing process. An immune response is energetically costly; your basal metabolic rate can rise by 10–15% when you have a fever.

We want to think about diet and lifestyle as preventative measures. How you enter the process of an infection will hopefully determine how well your body copes and responds to get rid of that infection, to a certain degree.

When we look at diet, how much we sleep and how much we move our bodies each day, these are all fundamentals that are tangible and that we can control. It’s important to explore how we can “bump them up a notch or two”, rather than making drastic changes and redesigning our lives – this just becomes a barrier to being consistent. Ultimately, consistency is what we are aiming for.

MC: There are so many “health myths” and pieces of misinformation circulating. Are there any examples of health myths that you would like to “set the record straight” on?

JM: The first one is around “boosting” your immune system. There is no scientific way in which we can do that. When your immune system is “switched on”, it makes you feel quite lousy. When you have a fever or a flu and you feel unwell, that’s because of inflammation in your body that occurs as part of your immune response to make your body hostile for pathogens. It can result in collateral damage on your own tissue, so we only want it to happen in a short-term, controlled way. Half of your immune system is therefore designed to turn this mechanism off when we don’t need it. It’s therefore not that you want to “boost” your immune system, but rather, you want it to be balanced.

There is also a lot of misinformation surrounding fasting and the effect it can have on your immune system, such as “resetting” it. In fact, those that would likely benefit from an “immune system reset” are not able to fast safely for a prolonged period.

We hear a lot about how we need to be eating “superfoods” to be well. In fact, we need to look at our dietary patterns holistically, not through a reductionist lens whereby one or two nutrients or fruits will satisfy our bodies and provide the nutrition that we need.

MC: Do you think that society knows what constitutes a healthy lifestyle and how we can take care of ourselves? Has this been influenced or impacted by the global pandemic?

JM: I think, unfortunately, we’ve lost touch with that.

We have concepts such as green prescribing happening in the United Kingdom, where an increasing number of GPs prescribe going outside for a walk, in nature. It really makes me think – when did we get to a point where we had to be told to do something as simple as that as part of our holistic health care?

We sometimes remove naturally occurring fiber from foods – which is incredibly important for our gut microbes – and then add synthetic fibers. Or we substitute a meal with a drink or a shake that’s advertised as being “healthy” but is probably more expensive and less nutrient-dense than a cooked meal. 

The aggressive marketing of food that is advertised as “healthy” because it contains one or two ingredients that are loosely linked to our well-being is problematic. It has gotten people really confused, and almost pathologized the feeling of being full after a meal, so many people now snack throughout the day rather than eating balanced meals.

Many of us also sit at a computer all day and then believe that we can undo this by spending a short amount of time at the gym. In fact, research tells us that we must break up sedentary time in addition to doing physical activity that increases our heart rate. We narrow down human movement requirements to these contrived pockets of time that we spend at the gym, but we need to think more about how we can move throughout the day and in lots of different ways.

Overall, we’re in a strange place. This becomes very clear to me when I speak to people of my parents’ generation; they often haven’t lost touch with the fundamentals. They cook at home, they know that they have to get fruit and vegetables in their diet, but they can have treats. They have a great relationship with food and movement – all the inputs that our immune system needs to keep well over the long term. Unfortunately, a lot of younger generations don’t have this anymore, and behaviors that negatively impact our immune system have become “the norm”. It means you have to work really hard to go against this, and develop habits that may be considered “unusual” to stay well.

MC: Could you talk about some of the key challenges that you encounter in your work? How do you envision overcoming them?

JM: There are quite a lot of challenges when measuring your immune system comprehensively. A lot of immunology research involves piecing together different tests modalities to create what I call an “immunobiography”. Your immune system is a product of your life in many ways, and how your life shifts and evolves over time, so we rely a lot on patient narratives and work to fit these different pieces together, which can be challenging.

I also think that we need to look at improving microbiome testing so that it can become more useful. The microbiome is a huge aspect of immunology research. Right now, we can look at stool samples and gauge an idea of what’s going on in the body, almost like a snapshot. But we are limited in how much that actually tells us and informs us about an individual’s health in a preventative way, rather than just reaching the stage of testing when intervention is required. I think tools that are evolving, such as machine learning and the ability to analyze large data sets, will collectively allow us to dive deeper and unpick more.

MC: In your opinion, what impact is the wellness industry having on our understanding of health and illness?

JM: I think that in some ways, the wellness industry can be beneficial because it encourages healthy behaviors to become a lifestyle for many people. It can encourage new activities and hobbies, and foster friendship groups and communities.

However, it can also encourage people to find themselves in situations where they feel that they can’t enjoy certain aspects of life because it goes against what the wellness industry prescribes. An example might be going out to eat pizza with a friend. Some people may choose to avoid that experience because they believe that the pizza is terrible for them. However, that time with your friend, the socialization and the activity in itself might overall be very good for you.

I think that there is a huge problem with the marketing aspect of the industry, which encourages people to buy products and drives consumerism and can adversely affect the environment. It can also exclude individuals from certain social economic backgrounds.

As a researcher, it's interesting to see more and more academics using social media channels and sharing information, which I think is fantastic. I get to learn about other fields that I'm interested in and collaborate with people to communicate science. However, sometimes messages can get overblown or taken out of context. Many people apply the information they learn from these sources to their lives to a tee, without understanding that science is constantly evolving, and new publications are released which can challenge information we previously thought to be correct. Without an understanding of the publication process and scientific training, the nuances of these processes may not be appreciated. 

MC: What do you envision the next 10 years will look like in terms of how people look at their health and the focus of immunology research?

JM: I think there will be a real shift towards personalized health, which we’re starting to see more and more. An example is the impact our genetics and environment can have on our ability to digest and process food – a field known as nutrigenomics. Identical twins, given the same meal, can produce very different blood sugar responses. Why is that? Considering these individual factors, it’s clear that we can’t have blanket guidelines – they need to be tailored.

I think that health psychology will play a huge role in how we look at health over the years to come. We have public health guidance, information and tips on what people should be eating and should be doing to take care of themselves, but people aren’t always doing that. Why? Because of how our lives are constructed. We’re often busy, stressed or tired. We’re bombarded with hyperpalatable foods that are tricky to resist. Health psychology, exploring ways in which to help people take action and live healthier lives, will definitely play an increasingly important role.

Dr. Jenna Macciochi was speaking to Molly Campbell, Senior Science Writer for Technology Networks.