Immunology: understanding our body’s defences
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Immunology: understanding our body’s defences
Immunology plays a critical role in medicine, helping scientists understand allergies, autoimmune disorders, and how the immune system fights infections and cancer. Dr Peter Bretscher, Emeritus Professor of Biochemistry, Microbiology and Immunology at the University of Saskatchewan in Canada, has dedicated his career to researching how the immune system operates and how it can be employed to improve health. Through his work, he addresses fundamental questions about how the immune system recognises invaders, avoids attacking our own bodies, and determines the best way to defend against threats.
Talk like an immunologist
Antibody — a protein produced by the immune system that binds to a specific antigen to neutralise or destroy pathogens
Antigen — a molecule, often found on the surface of a pathogen, that the immune system recognises and targets
Autoimmunity — a condition in which the immune system attacks the body’s own tissues, mistaking them for harmful invaders
Pathogen — a harmful organism, such as a bacterium, virus, fungus or parasite, that can cause disease
Self-antigen — a molecule naturally present in the body that the immune system typically learns to tolerate to prevent attacking its own tissues
Imagine a world without vaccines, where even a minor infection could turn deadly. The science of immunology has transformed medicine and saved countless lives by developing effective vaccination against many infectious diseases. Current research holds promise for preventing and treating cancer, allergies and autoimmune disorders such as type 1 diabetes and multiple sclerosis, and those infectious diseases not contained by standard vaccination.
“The immune system is a collection of mechanisms, present in vertebrates, that has evolved to attack foreign invaders,” explains Dr Peter Bretscher, Emeritus Professor of Biochemistry, Microbiology and Immunology at the University of Saskatchewan. “Though immunity was recognised by the ancient Greeks, immunology only became a science when, in the mid- to late 1800s, Louis Pasteur in France and Robert Koch in Germany established the germ theory of infectious disease.” Pasteur’s groundbreaking work led to new ways of vaccinating, using weakened pathogens to train the immune system to remember and respond more effectively to an invader. Today, immunology is more relevant than ever. Whether it is through innovative cancer therapies or life-saving vaccinations, the study of immunology proves that understanding our body’s defences is key to shaping a healthier future.
What are the big questions in immunology?
Immunologists are driven by two fundamental questions: why does the immune system sometimes attack the body it is meant to protect, and how does it decide which tools to use against a foreign invader?
The first question addresses autoimmunity, which occurs when the immune system mistakenly targets the body’s own molecules. “Most people do not suffer from autoimmunity,” says Peter. “The occasional occurrence of autoimmunity shows we have the potential to generate immunity against self-molecules, called self-antigens.” Normally, foreign antigens – molecules from harmful invaders like bacteria or viruses – provoke an immune response, while self-antigens prevent it. But how does the immune system differentiate between these two outcomes?
The second question explores how the immune system determines its method of attack. It has a variety of tools at its disposal, from antibodies that neutralise pathogens to specialised cells that directly destroy infected cells, referred to as cell-mediated immunity. How the immune system decides which response to deploy is critical to understanding and treating diseases like cancer, where only cell-mediated immunity is effective. “We refer to these two questions as ‘To Be or Not To Be?’ and, ‘If To Be, What To Be?’” says Peter.
What is the significance of distinct classes of immunity?
The immune system’s ability to distinguish self from non-self is only part of the story. Equally important is how it decides how to respond to different threats. “There are two main classes of immunity, those mediated (accomplished) by antibody molecules and those mediated by cells,” explains Peter. These distinct approaches allow the immune system to deal with a wide variety of invaders, from viruses and bacteria to cancer. “However, only cell-mediated immunity is effective against cancer and, for example, those pathogens that cause tuberculosis and AIDS,” says Peter. “Also, the consequences of any immunity directed against self-antigens depends on the class of immunity expressed. For example, cell-mediated immunity is often more damaging than the production of antibodies.”
How does autoimmunity arise?
Autoimmunity occurs when the immune system attacks the body’s own tissues. Central to this process are cross-reactive antigens – when both foreign invaders and the body’s own cells share structural features. Antibodies, which are highly specific, normally bind only to the exact antigens they are designed to target. However, when two antigens – let us call them R and Q – are similar in structure, antibodies that bind to R might also bind to Q. “For example, an infection with group A streptococci bacteria can sometimes lead to rheumatic heart disease,” explains Peter. “In this condition, the immune system produces antibodies to fight the bacteria, but some of these antibodies also bind to similar molecules in heart tissue, causing the immune system to attack the heart.”
What are the key achievements in immunology?
In recent decades, immunologists have made significant progress, particularly in understanding how the immune system produces antibodies and how it avoids attacking the body’s own cells. One of the field’s most important achievements is the development of The Clonal Selection Theory in the 1950s. This theory revolutionised our understanding of how the immune system recognises and responds to foreign invaders while preventing the production of antibodies against most self-antigens.
“The theory proposes that each immune cell is programmed to produce just one unique antibody,” says Peter. “When these cells first emerge, they are destroyed if they interact with self-antigens, ensuring that most of the body’s own tissues aren’t attacked.” However, if these cells do not encounter particular self-antigens, not present in the organ where the immune cells are generated, they remain alive and are ready to be activated when exposed to foreign invaders. When a pathogen is detected, the immune system selects the specific cells that can recognise it, allowing those cells to multiply rapidly and produce large quantities of antibodies. This theory has been crucial in explaining how the immune system can respond so effectively to infections.
Reference
https://doi.org/10.33424/FUTURUM559
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Despite its success, The Clonal Selection Theory is not the complete answer to all questions in immunology. While it provides a solid foundation for understanding how the immune system recognises foreign invaders, there are still many unknowns. For example, how exactly does the immune system decide which response to deploy in different situations (such as for cancer) where the type of response (antibody- or cell-mediated) is critical? How can we better prevent autoimmunity and improve treatments for diseases like multiple sclerosis, and autoimmune diabetes, AIDS and tuberculosis? These are just some of the ongoing challenges that researchers like Peter are working to address.
About immunology
Immunology is the study of the immune system, the body’s natural defence against infectious diseases. The field explores how the immune system protects us from harmful pathogens like bacteria (that cause, for example, tuberculosis), viruses (that cause, for example, AIDS) and fungi, while maintaining tolerance to the body’s own tissues. Immunology is also central to understanding how the body protects against cancer, and how autoimmune disorders and allergies can be prevented and treated.
Immunology has advanced significantly since its inception in the late 19th century. Today, immunologists investigate questions such as how the immune system distinguishes between self and non-self, why it sometimes attacks the body, and how it decides the best strategy to combat invaders. These insights have paved the way for groundbreaking treatments, including immunotherapy for cancer and vaccines for infectious diseases.
One of the most exciting aspects of immunology is its universality. “The attribute of universality means the immune system can produce antibodies to all foreign substances, even those not previously encountered,” says Peter. “How can this be? The miracle required is illustrated by a parallel question: how can a key shop have all the keys to all the locks, some of which have yet to be invented?” The answers to these questions, developed over decades, have transformed our understanding of biology and medicine. And for those entering the field, the rewards are both intellectual and practical.
“Today, immunology is a more established field,” says Peter. “We are seeing that basic understanding allows us to imagine and find ways to prevent and treat diverse immune system-related diseases in the most delicate and unobtrusive means. It is happening!”
A Spiral Approach for Understanding Contemporary Immunology
“Science progresses in steps of understanding. Concepts developed at one stage are used as building blocks or modified in the next,” explains Peter. “The subject of immunology is about 250 years old. The best way to gain an understanding of our sophisticated view today is by tracing how the simplest ideas first arose and then had to be modified in view of further observations. I have written a one-, a ten- and a twenty-page document, reflecting successive stages of understanding. I think successively studying this ‘spiral immunology’ is the most effective way of getting to grips with contemporary issues of the subject. I hope you enjoy these and would love to hear what you think about this approach to a contemporary science.”
You can read Peter’s spiral immunology articles and message him via the comment box at the bottom of this page.
Pathway from school to immunology
To pursue a career in immunology, take courses in biology, chemistry and physics to gain a solid foundation for understanding the basic principles of science. Mathematics is also important, as it is often used in data analysis and modelling in immunological research.
“The most valuable traits a student needs, to be a successful researcher, are curiosity and passion,” says Peter. “If you have those for any subject, immerse yourself in that subject.”
At university, a degree in biology, biochemistry, microbiology or a related field is a common starting point. Courses in molecular biology, genetics and cell biology are particularly relevant.
Many universities and research institutes offer opportunities for high school students to work in laboratories, gaining hands-on experience in scientific research, including immunology-related projects.
Explore careers in immunology
Careers in immunology are diverse, ranging from academic research and clinical trials to biotechnology and pharmaceutical development. Immunologists work on developing vaccines, creating therapies for autoimmune diseases, and improving treatments for allergies and cancer. They are also involved in public health initiatives, such as designing strategies to combat pandemics.
“People are different, with different gifts. That is why specific advice is often less valuable than giving encouragement for self-directed exploration and discovery,” says Peter. “Explore Immunopaedia and see which items particularly intrigue you.” Such websites provide excellent resources, offering educational materials and updates on research opportunities in immunology.
According to Talent.com, the average immunology salary in Canada is $98,000 per year.
Q&A
Meet Peter
What experiences have shaped your career?
I was fascinated by physics and philosophy as a teenager. I was overwhelmed by the power of ideas in physics to provide compelling insights into nature. I was fascinated by theory and dreamt of the possibility of making theories myself. I studied physics at Cambridge University in the UK. However, I did not feel confident during my undergraduate studies that I could ever make significant theories in physics; I thought I might be able to do so in biology. So, I enrolled in a PhD programme at the Cambridge Laboratory of Molecular Biology. This was a pioneering laboratory. During my studies, I became very interested in theoretical aspects of immunology. I availed myself of an invitation, on a notice board outside the office of Francis Crick, the co-discoverer of the structure of DNA, to discuss science. A few discussions ensued, and I never looked back.
What has motivated your research choices?
Wise researchers choose research questions that are approachable. I chose the most basic questions that I thought approachable, concerning how immune responses are regulated, namely the mechanistic basis of self/non-self discrimination and of immune class regulation. There was much information, pertinent to these questions, that was not accounted for by any framework when I entered the field in the late 1960s, so I had great fun in trying to develop such frameworks. These frameworks appear to have more than stood the test of time.
How do you overcome challenges in your work?
There are usually more paths offered in life than we imagine when we find ourselves challenged. If we manage to keep our long-term passion alive, we will usually find, eventually, that we have the resilience to transcend challenges.
What are your proudest career achievements?
I remember the first time we showed that infection with a few pathogenic organisms generated both an exclusive cell-mediated response and, in time, a ‘cell-mediated imprint’. This pathogen could only be contained by a cell-mediated response, not by antibody. We used animal models to test our idea. Two months after exposure to a few organisms, we challenged the animals with a high number of organisms that, in naïve animals, rapidly generated a predominant antibody response and progressive disease. Our exposed animals generated a sustained cell-mediated response and contained the pathogen. We had demonstrated a basically conceived strategy to vaccinate against pathogens uniquely susceptible to cell-mediated attack. Was this the solution to vaccination against cancer, AIDS and tuberculosis? Exciting! Human trials will, in the end, provide a definite answer.
What are your aims for the future?
I feel we, as members of contemporary society and, in my case, as an immunologist, have been adversely affected by the information overload. We tend to think we do not know enough to realise our aspirations! I am occupied by the question of how we can give life meaning under these circumstances. Doing scientific research has reinforced my faith in our ability to see the big picture and in the value of doing so. Only by seeing a big picture can I be motivated to realise my aspirations.
Peter’s top tips
1. Pay attention to what is needed to keep your curiosity and passion alive.
2. There are always external pressures indicating what you must do to be successful. When you feel such pressures, slow down rather than speed up.
3. Consider what is required to maintain your integrity and your ability to make your unique contribution.
Do you have a question for Peter?
Write it in the comments box below and Peter will get back to you. (Remember, researchers are very busy people, so you may have to wait a few days.)
Learn more about immunology and vaccinology:
www.futurumcareers.com/how-can-we-develop-more-effective-vaccines
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