My name is Simi and I love immunology.

Why immunology? This is a question I ask myself every day… and admittedly even now as I write this blog. What if I told you that we encounter billions of weird, gross and potentially harmful foreign substances, better known as antigens, that want to start a war inside us. Yes… a war. What if I also told you that our body is equipped with a state-of-the-art built-in defence system to fight these invaders called the immune system. Sit back and breathe in the harmful beauty that surrounds you now, as I explain why I chose immunology.

Day and night, a specialised task force of cells called B cells patrol our bloodstream in search of invading antigens. Every antigen has a specific appearance, for example, some bacteria are covered with a molecule called lipopolysaccharide (LPS). B cells can recognise this structure, activating the production of bespoke, tailor-made proteins to neutralise the threat; these Y-shaped proteins are called immunoglobulins (or antibodies in ‘non-nerd’ terms).

Antibodies have two regions: a variable region and a constant region (Image 1). The variable region can specifically recognise and bind to invading antigens. On the other hand, the constant region, although not specific, determines how the antigen will be destroyed and is important for sounding the alarm and alerting other immune cells of the potential threat ¹. For example, it can attract hungry killing machines called white blood cells that can swallow and destroy the whole antigen (or in nerd terms: phagocytosis) in a process called opsonization.

The constant region has 5 main classes: IgM, IgD, IgG (IgG1,2,3 and 4), IgA (IgA1 and 2) and IgE; each type can be found in different parts of the body and have different functions (Image 2). Several different factors, such as cytokines (small proteins produced by cells of the immune system) can activate B cells to change the class of the constant region in a process called antibody class switching; this process can help the antibody become better at fighting the invading antigens and win the war ³.

Therapeutic antibodies (antibodies used to treat diseases) are one of the fastest-growing drug classes, with thousands currently undergoing approval. However, all of the antibodies that have been approved thus far are IgG antibodies, with none being approved of any other antibody class. This is mainly due to a lack of knowledge and research about what controls antibody class switching and the difference that this makes to the immune response overall ⁵.

This is where my project comes in. I will be working with Professor Deborah Dunn-Walters and we will be looking at (drum roll please…) antibody class switching in vitro; in vitro simply means using cells and tissues outside of their natural environment, so in my case, human B cells. What will I be doing? Well… I will be adding lots of different factors such as cytokines to these B cells to see the effect they have on class switching, or more specifically, what class of antibody is produced. Sounds simple enough right? Let’s hope so!

Antibodies are only one type of protein involved in the complicated symphony that is our immune system. Gaining a greater understanding of how these molecules work, change and interact can help develop better and more effective vaccines and drugs which could be invaluable for treating diseases more efficiently, such as IgE in skin cancers or IgA in gut-related disorders.  So why immunology? This isn’t just about microscopic molecules fighting wars, it’s about the bigger picture – the potential to change the outcomes of the treatments available today and those yet to come. Heroes come in all shapes and sizes and this time, it’s Y.

My name is Simi and I love immunology. Hopefully now you know why 🙂

Further reading and references:

1. Schroeder H, Cavacini L. Structure and function of immunoglobulins. Journal of Allergy and Clinical Immunology. 2010;125(2):S41-S52.
2. Feature: Evolution Inside Us [Internet]. BlueSci. 2019 [cited 11 December 2019]. Available from: https://bluesci.wordpress.com/2009/10/01/feature-evolution-inside-us/
3. Stavnezer J, Schrader C. IgH Chain Class Switch Recombination: Mechanism and Regulation. The Journal of Immunology. 2014;193(11):5370-5378.
4. Types of antibodies [Internet]. Ruo.mbl.co.jp. 2019 [cited 11 December 2019]. Available from: https://ruo.mbl.co.jp/bio/e/support/method/antibody-isotype.html
5. ElBakri A, Nelson P, Abu Odeh R. The state of antibody therapy. Human Immunology. 2010;71(12):1243-1250.