How do immune cells ‘evolve’ to protect us?
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How do immune cells ‘evolve’ to protect us?
Your immune system is constantly updating to protect you from harmful diseases, but how does it do this? At Western University in Canada, Dr Steven Kerfoot and his team of immunologists are studying the interactions between B cells and T cells in the immune system and exploring how malfunctions can lead to the development of autoimmune diseases.
Talk like an immunologist
Antibody — a B cell receptor that is no longer attached to a B cell
Antigen — a foreign substance that triggers an immune response, such as a part of a virus or bacterium protein
Autoimmune disease — a disease that occurs when the immune system mistakenly identifies molecules on a healthy cell as antigens and attacks them
B cell — a type of white blood cell that recognises antigens (each B cell recognises a unique antigen)
B cell receptor — the part of a B cell that binds to antigens directly
Multiple sclerosis (MS) — an autoimmune disease caused when myelin is damaged, with symptoms including fatigue, difficulty walking and vision problems
Myelin — the protective substance that surrounds nerve axons
T cell — another type of white blood cell that recognises antigens, but cannot bind to them directly, so other cells have to ‘show’ the antigen to T cells
“We all have an immune system to protect us from things that are trying to infect us,” says Dr Steven Kerfoot, an immunologist at Western University. Whenever you develop a cold or pick up a new infection, B cells and T cells in the immune system share the job of identifying the harmful antigen. They can then attack it, or direct other immune cells to attack the invader. Steven and his team are researching how B cells and T cells interact with each other as the immune response to a new antigen develops.
How do B cells and T cells fight infections?
“B cells work by binding directly to an antigen using a feature on their surface called a B cell receptor,” explains Steven. “They can also produce multiple copies of the B cell receptor which, once released to float around the body, are called antibodies.” But at first, a B cell does not know if the antigen it recognises is something it should attack or not. To find out, it must bind to the antigen and show it to a T cell that also recognises the same antigen. In this way, T cells and B cells that recognise the same antigen form a partnership to guide the development of the immune response to the new target.
“You have millions of B cells, and each recognises its own antigen,” explains Steven. In the same way that each basketball player defends against a specific player on the other team, each B cell is responsible for defending against a specific antigen. For the immune system to work effectively, the B cell receptors and antibodies must stick to the antigen very strongly. The problem is, at the start of the immune response they usually do not stick very well, so to become effective, B cells must ‘evolve’ each time the body encounters a new threat.
How do B cells ‘evolve’?
The first step in B cell ‘evolution’ happens when a B cell meets a new antigen. At first, it will not be good at binding to this unknown antigen, but it immediately begins to replicate itself to create identical clones. “Each of the clones then begins to mutate its gene for producing the B cell receptor,” explains Steven. As with all mutations, some are advantageous and some are disadvantageous. “This means you end up with some B cells that are better at binding to the new antigen and some that are worse.”
Once the B cell clones have mutated, the race is now on, as only the B cells that are most effective at binding to the antigen and carrying it to the T cells will survive. “All the new B cells essentially have a massive fight to the death!” says Steven. “Those that can’t grab the antigen will die.”
The most effective B cells will survive and replicate, producing a new generation of clones, which again mutate themselves. And of these new mutations, some will be even more effective at binding to the antigen and will therefore go on to replicate themselves. In this way, over a period of 10 to 14 days after exposure to a new antigen, B cells ‘evolve’ to become ever more effective at binding to it. “Once your immune system has ‘evolved’ B cells that can fight that particular antigen, the next time you get infected (or the first time, if your initial introduction to the antigen was through a vaccine) your B cells will be ready to produce effective antibodies straight away,” says Steven.
What research is the Kerfoot Lab conducting?
“In my lab, we’re interested in the interactions between B cells and T cells,” says Steven. “Once a B cell has captured an antigen, it needs to take it to a T cell and receive a signal to acknowledge it as a ‘successful’ mutation, which can then go on to produce antibodies and replicate itself.”
The team is looking at the properties of antigens to understand how changing the quality of the antigen might impact the interaction between B cells and T cells. This involves creating new hybrid antigens and introducing them to genetically modified mice with B cells and T cells that have been programmed to recognise different parts of antigens. “We can ‘mix and match’ different B cells and T cells by engineering hybrid antigens so that the B cells will recognise one part of the antigen and the T cells will recognise another,” says Steven. “By changing the combinations, we’re trying to understand how that impacts the immune response.”
As a master’s student in the Kerfoot Lab, Eden Kemal was involved in designing and making these new hybrid antigens and measuring the outcome of the B cell response. “I discovered that we can improve a bad B cell response by putting a strong T cell in charge of it,” she says.
The team is also studying what happens when the signals between B cells and T cells do not work as they should. Some B cells mistakenly identify molecules on healthy cells in the body as antigens and attack them, leading to autoimmune diseases. For example, if B cells attack myelin in the brain, it causes multiple sclerosis (MS). “In this case, the signals between B cells and T cells aren’t very good, and we’re trying to understand why this is,” says Steven.
PhD student Yi-Han Chen is studying the interactions between these malfunctioning B cells and T cells. “My findings indicate that the immune system might have a previously unrecognised mechanism which limits these harmful B cells,” he says. “This is something we’re excited to explore further.”
These projects give the Kerfoot Lab plenty to study, and the team is looking forward to seeing what they discover next!
Dr Steven Kerfoot
Department of Microbiology and Immunology, Western University, Canada
Field of research: Immunology
Research project: Investigating interactions between B cells and T cells and how they control B cell immune responses
Funders: Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institutes of Health Research (CIHR)
Website: kerfootlab.com
Reference
https://doi.org/10.33424/FUTURUM629
Students at work in the Kerfoot Lab.
A student takes care of cells in a bio safety cabinet in the lab.
All images © Steven Kerfoot
About immunology
Immunology is the study of the immune system. “The immune system is a finely tuned system,” says Yi-Han. “It protects us from infections but, when it goes out of balance, it can also harm our own bodies. Understanding how it works is not only fascinating but also important for improving human health.”
What does a day in the lab involve?
“A typical day in the lab often starts with data analysis from previous experiments, which helps me plan my next steps,” says Yi-Han. “On days when I conduct experiments, I usually start early since many procedures take several hours to complete.” Yi-Han also spends time ensuring that the mice involved in the lab’s experiments are healthy and well-cared for. “Working with animals and doing hands-on experiments is a privilege as it gives us a powerful way to understand how the immune system works.” During her master’s project, Eden’s days in the lab involved harvesting cells from mice, staining them so she could observe certain markers, and imaging them to view the cellular architecture.
The joys of being an immunologist
“The most rewarding part of working in the Kerfoot Lab was collaborating and engaging in the scientific process with other lab members,” says Eden. “It’s amazing to see a final product come together that was only possible due to shared knowledge.” For Yi-Han, studying immunology is rewarding because it provides opportunities to constantly learn and grow as a scientist. “During my PhD, I have developed several new scientific techniques to study B cells,” he says.
The importance of immunologists was globally recognised with the development of the COVID-19 vaccine, which changed the course of the worldwide pandemic and saved over 20 million lives in the first year after its release. Working as an immunologist is an incredibly rewarding career, with the opportunity to contribute towards the development of new vaccines for infectious diseases and new treatments for autoimmune diseases and cancers, improving the lives of countless people.
Pathway from school to immunology
During high school, study biology and chemistry. Other science subjects will also be useful, as well as subjects that will develop your communication skills, such as English.
To become a research immunologist, study immunology, microbiology, biochemistry or biology at university. To become a clinical immunologist, you will need to study a medical degree and then specialise in immunology during your practical training.
Look for opportunities to gain hands-on research experience. This could be as a student researcher in a university immunology lab or through summer schools.
Explore careers in immunology
Some research immunologists, like Steven, conduct scientific experiments in a lab to learn more about the immune system, while others use this knowledge to develop new vaccines against infectious diseases and treatments for problems with the immune system.
Clinical immunologists are medical doctors who diagnose and treat patients who have problems with their immune system, such as autoimmune diseases, allergies or an inability to fight infections.
CareerExplorer provides information about the pathways to becoming a research or clinical immunologist and what the different careers could involve: careerexplorer.com/careers/immunologist/how-to-become
Meet Yi-Han
Yi-Han Chen is a PhD student in the Kerfoot Lab.
As a teenager, I was fascinated by the idea of exploring the unknown. I immersed myself in books about history and geography, imagining the places and cultures I hadn’t yet visited. Now, I explore the unknown through science!
I was inspired to study immunology by the revolutionary success of cancer immunotherapy. The idea of harnessing the immune system’s natural ability to target cancer cells fascinated me. Eager to learn more, I joined an immunology lab during my final year of university in Taiwan. That hands-on experience solidified my interest in the immune system and its potential, leading me to pursue graduate studies in immunology.
During the COVID-19 pandemic, my interest in immunology deepened further. Vaccination is the most effective way to protect against the virus, and I found my interest shifting to how immune protection is built and maintained. I was fortunate to find the Kerfoot Lab in Canada as the lab’s focus aligned perfectly with my growing interest, and I believe Dr Kerfoot’s mentorship will shape me into a confident and capable researcher.
After completing my PhD, I hope to pursue a postdoctoral fellowship in the fast-moving field of biomedical science. Working in the Kerfoot Lab has prepared me for this path. By designing experiments, developing new techniques and troubleshooting complex problems, I’ve gained technical experience and scientific confidence. These skills will help me navigate future challenges and grow as a researcher.
In my free time, I enjoy taking pictures. Photography helps me discover stories in everyday life and has greatly improved my storytelling skills. I also enjoy playing tennis. The rhythm of striking the ball back and forth is very satisfying, and it’s a great way to clear my mind and stay active.
Yi-Han’s top tips
1. Stay curious and passionate about science.
2. Seize every opportunity to explore and learn.
3. Never stop asking questions – each one brings you a step closer to becoming a skilled and competent researcher.
Meet Eden
Eden Kemal is now a medical student, having previously worked in the Kerfoot Lab as an undergraduate and master’s student.
At school, biology was always my favourite subject. I loved learning how the human body works. Outside of school, I enjoyed spending time outdoors, especially cycling to nearby parks with my friends. I also enjoyed volunteering in different settings (including at summer festivals, a daycare centre and hospital gift shops), as it gave me the chance to meet new people and hear about their diverse life experiences.
I was first exposed to the world of immunology as a second-year undergraduate student when I joined the Kerfoot Lab as a work-study student. Hands-on experience in an immunology lab allowed me to deepen my interest in the immune system. During my four years in the lab, I was fortunate to learn from senior students, the lab manager, Heather, and Dr Kerfoot.
Working in the Kerfoot Lab helped prepare me for medical studies, and I am now at medical school. I came to understand the value of learning from mistakes, and I learnt how to approach problems with a resilient and growth mindset. I truly learnt that just because something doesn’t work the first time, it doesn’t mean you have failed. Instead, it presents an opportunity to learn something new. This mindset is critical in medicine, where challenges are always present and resilience is key. Learning how to seek help from others, reflect on mistakes, and adapt to new approaches has helped me grow both as a researcher and future physician.
In my free time, I love gardening with my family and taking care of my indoor plants. I also enjoy crafting clay pottery, exploring new cafés and going thrifting.
Eden’s top tips
1. Be curious and open-minded about science.
2. Science is such a broad field, so try different activities, classes and opportunities to find out what really sparks your interest. Once you discover what excites you, learning becomes so much more enjoyable.
Do you have a question for Steven, Eden or Yi-Han?
Write it in the comments box below and they will get back to you. (Remember, researchers are very busy people, so you may have to wait a few days.)
Learn more about the immune system and how scientists develop vaccines:
futurumcareers.com/how-can-we-develop-more-effective-vaccines
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