To recap from last time, we learned that:
(1) Immune cells are all derived from a common precursor stem cell in the bone marrow.
➪ Many myeloid cells make up the innate immune system.
➪ Many lymphocytes make up the adaptive immune system.
(2) Innate immune cells are the frontline responders when holding off any invading microbe.
(3) Adaptive immune cells are stronger reinforcements that:
➪ Combat a specific pathogen.
➪ Are responsible for “immunological memory”.
(4) B cells and T cells are adaptive lymphocytes that express a B cell receptor (BCR) or T cell receptor (TCR) on their surface.
Today, we’re going to cover the different combat tactics of B cells and T cells! Just like any effective battalion, your adaptive immune system possesses ranged, assist, and melee fighters.
The following sections will describe:
(1) The development of B cells, and their role in producing antibody.
(2) The development of T cells, and their roles in helping B cells and killing infected cells.
B cells are ranged fighters, as they are responsible for making antibodies.
As explained previously, B cells express a B cell receptor (BCR) on their surface. The BCR is shaped a lot like a “Y”. The top “V” part of the “Y” is called the variable fragment, and the bottom tail is called the constant fragment.
The variable fragment is responsible for binding to molecules made by pathogens. In a healthy individual, the variable fragment will recognize only these foreign antigens, and not molecules that are made in your own body.
It is important to remember that:
(1) Each individual B cell can forge only one type of variable fragment.
(2) All B cells in your body have a unique variable fragment in their BCR.
I’m going to make one distinction here. The unique variable fragments from two B cells can bind to two completely different antigens. However, they can also bind to two different sites on the same antigen, called epitopes. The following diagram makes this a lot more clear:
When an antigen binds to the variable fragment, the function of the constant region is to send a signal down to the B cell and alert that a pathogen is nearby. The B cell will then make lots of copies of itself. This is called clonal expansion. The B cells will then “level up” into plasma cells. The plasma cell will push its BCR production into overdrive, and release these BCRs from its surface. These discharged BCRs are what we know as antibodies!
Antibodies can be useful in many ways:
(1) Antibodies can bind to virus particles and prevent them from entering cells.
(2) The constant region can be recognized by innate immune cells such as neutrophils, which will “eat” and “digest” antibody-coated virus particles.
To summarize:
(1) B cells express a BCR on their surface, which has variable and constant fragments.
➪ The variable fragment of the BCR will bind to foreign antigens.
➪ The constant fragment of the BCR will signal to the B cell to clonally expand.
(2) After clonal expansion, B cells will “level up” into plasma cells.
(3) The plasma cells will release their BCRs as antibodies.
(4) Antibodies function by:
➪ Stopping viruses from entering cells.
➪ Encouraging neutrophils to eat viral particles.
Next up: how do T cells protect us?
T cells come in many flavours, and they can help B cells or kill infected cells.
As explained previously, T cells express a T cell receptor (TCR) on their surface. You can think of a TCR as a single “arm” that is found on the variable fragment of an antibody. Similar to B cells, each individual T cell can forge only one type of TCR.
The unique TCRs from two T cells can bind to two completely different antigens. Alternatively, these TCRs can also bind to two different epitopes on the same antigen. Upon activation, T cells will clonally expand, just like B cells.
However, T cells are much pickier than B cells! They can’t recognize just any old antigen lying around. They need the antigen to be presented to them on a special protein called MHC. Dendritic cells are really good at doing this and have high levels of MHC on their surface, so they are called professional antigen-presenting cells. However, many of your normal body cells are also capable of presenting antigens on MHC.
You may have noticed that the T cells in the above diagram are coloured a little differently, one in light green and the other in dark green. This is because there are several flavours of T cells, but today I will be focusing on just two.
Firstly, we have the CD4 T cells, also called helper T cells. Fitting with their name, helper T cells will not directly act upon viral particles or infected cells, but will boost the function of other innate and adaptive immune cells. For example, a special class of helper T cells is responsible for stimulating B cells to develop into plasma cells.
Helper T cells will also assist in the activation of a second flavour of T cells. These are called CD8 T cells or cytotoxic T lymphocytes (CTLs). CTLs will directly kill infected cells.
To summarize:
(1) T cells express a TCR on their surface that will only recognize antigens presented on MHC.
(2) Upon activation, T cells will clonally expand.
(3) There are two main flavours of T cells.
➪ Helper T cells will assist in the activation of B cells and cytotoxic T lymphocytes (CTLs).
➪ CTLs will directly kill infected cells.
Whew! That was a lot of information. Now that we’ve browsed through the battle tactics of the adaptive immune system, we can finally get to the meat and potatoes. In the next edition of Sidebar, I’ll be discussing how vaccines work, and the different types of vaccines we have made so far to combat viruses. We will then move on to current SARS-CoV-2 vaccine efforts.
In the near future, I hope to cover the principles of SARS-CoV-2 antibody testing. I also believe that there is a lot of interest in the interplay between pregnancy, antibodies, and SARS-CoV-2 infection. I will be collaborating with William Ding, another COVID-19 Demystified author, to soon publish another fascinating article on transplacental antibody transfer. Stay tuned!
References
- Chaplin, D. D. Overview of the immune response. J Allergy Clin Immunol 125, S3–23 (2010).
- Marshall, J. S., Warrington, R., Watson, W. & Kim, H. L. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol 14, 49 (2018).
- Murphy, K. & Weaver, C. Janeway’s Immunobiology. (Garland Science, Taylor & Francis Group, LLC, 2017).
