Continuing with my sub-series on vaccines this week I am going to have a bit of a look at the theory behind how vaccines do their jobs inside us. Next week I’ll look at how they work at a community level. First it’s worth defining what it is that a vaccine is supposed to achieve after is it is administered. Once we know our end point it should be easier to identify our journey. Unfortunately this means this post will only deal with vaccines right at then end and only very briefly, this is an immunology post in disguise.
The goal of every vaccine is to induce lifelong protection for the patient from the specific nasty of interest. But in order to understand how one would receive ‘lifelong protection’ following the injection of a dead or weakened nasty, or even just the bits of one, we need to go backwards a bit and have a look at how we develop an immune response.
Now before I get into this I feel the need to reiterate a point I have made before, that time in regards to cardiac physiology. This is not a high-end medical journal, and as such I will skip over some points that, while important, may not be entirely relevant. So please don’t look at me over the top of your glasses and tsk tsk me, I’m trying to do the right thing.
Lets start at the beginning. The immune system is derived from stem cells in the bone marrow known as the haematopoietic stem cells. These cells undergo haematopoiesis to give rise to all the blood cells, red and white (and perhaps blue too, but only in the most patriotic of Americans).
If we start at the top we can see a family tree of cells that ends up with a huge variety at the bottom. In order to go from the top to the bottom we need to continually differentiate these cells into specific cell types. On the left we have the myeloid cells. Myeloid cells include our red blood cells (Erythrocytes) and platelets (Thrombocytes) and members of the innate immune system known as the granulocytes and PMN’s (polymorphonuclear neutrophils, fancy way of saying the nuclei in these cells looks funny). But for our discussions of vaccine function we need to look to the other side. The lymphoid lineage.
As an aside the ‘B’ comes from the anatomical location of B cell development, the bone marrow. ‘T’ stands for ‘thymus’, which is an organ found just above the heart and is the location for T cell maturation.
B and T cells form the heavy-duty workhorses of the immune system and each has two distinct roles. Let’s start with the B cells. B cells mature in the bone marrow and then enter your circulation as a naive B cells. In this state they don’t do very much but are primed to detect a foreign epitope. An epitope is a fancy word for shape but this shape is very important, it must fit into another specific shape determined by the B cell receptor protein – a so called ‘lock and key’. If the B cell comes into contact with the epitope that fits its ‘lock’ then the B cell goes a bit nuts. The maturing B cell undergoes huge gene expression changes and the result is that the immature B cell becomes one of two different cells, a plasma cell or a memory B cell.
Plasma cells are the source of antibodies and it is antibodies that are the active structures that fight the detected foreign invaders. To wildly generalise antibody function we could say that they act as signals to other parts of the immune system that say “OVER HERE!!! THIS SHOULDN’T BE HERE!!! DESTROY DESTROY DESTROY!!!”
The other cell is a memory B cell, guess what that does…
These cells do not become plasma cells but in many ways are similar to the immature B cell in so much as they go back to floating around in the circulation waiting to see the epitope again and once they do they can become plasma cells and more memory cells. In this way the immune system can ‘remember’ what foreign epitopes it has seen before. The difference between the immature and memory cell is that the memory cell is less flexible in regards to how many ‘keys’ will fit into its ‘lock’ but is much better at responding to any key that does fit.
Similarly T cells also undergo a maturation process in the presence of a specific epitope. After migrating from the bone marrow to the thymus and then the thymus to the blood stream the inactive T cells wait to encounter their epitope of interest but T cells need a little extra help. The epitope has to be shown to the T cell in another molecule known as the major histocompatibility complex or MHC. In any case after the T cell sees its epitope it too will mature and we get two different types of cells, memory T cells and effector T cells. Unlike B cells that have only one type of effector cell, the plasma cell, the effector T cells can be classed as either cytotoxic, helper or regulatory depending on what they end up doing. The T cells that do the killing are the cytotoxic T cells and they function by killing any cell that presents the foreign epitope inside MHC.
After all that there are three points that need to be made. B cells make plasma cells that make antibodies that attach to the outside of foreign objects and mark them for destruction. T cells make cytotoxic T cells that are guided to cells that contain foreign objects inside them and when they find these cells they tell them to die. Finally, both cells, after being activated, give rise to a sub-set of cells that ‘remember’ that the foreign epitope has been around before.
One of the advantages of remembering an experience rather than having to respond to it ‘as new’ every time is that with practice you get better. The second and subsequent times you see a particular epitope your immune response is harder, better, faster, stronger.
So after all that we can now address the question of how does a vaccine work?
Vaccines act as practice for your immune system. The first time you see the nasty your immune system is slow but each subsequent time it is better so why not have your first exposure be billed as immune system Vs. weakling rather than immune system Vs. full blown nasty.
The concept of ‘immunological memory’ is fundamental and would exist without vaccination but through vaccination we can exploit it. As well as developing a memory it’s important to develop the right kind of memory. As I mentioned above plasma (B) cells flood an area with antibodies that bind to foreign bodies and signal their attack and removal but this response is less than effective when the foreign body is hidden away inside a cell. In that case a T cell which, because of the presence of an altered MHC molecule signalling to it, can detect cells with parasites inside and then direct the death of that cell would be more effective. This accounts for the range of vaccine styles are described last week because vaccines are all about developing the right memory for the immune system to use as a foundation for all future encounters.
Bonilla FA, & Oettgen HC (2010). Adaptive immunity. The Journal of allergy and clinical immunology, 125 (2 Suppl 2) PMID: 20061006
Lefrançois L, & Obar JJ (2010). Once a killer, always a killer: from cytotoxic T cell to memory cell. Immunological reviews, 235 (1), 206-18 PMID: 20536565