I hate to break it to you, but I’m afraid you have a potentially life-threatening disease; in fact you have quite a few. Aren’t you fortunate that you have the most sophisticated protection system ever devised fighting to keep you healthy? If I took away your immune system right now you most likely would not live to read my next post. What would kill you would be the everyday bacteria, viruses and fungi that are, quite literally, on everything you touch, eat, drink or breathe, and are trying to use up the precious resource that is your body as your read this now. Luckily for you, I’m not going to take your defences away, but I will try and give you a deeper understanding and appreciation of this incredible system and what we know about how it works.
The innate immune system - stone-age defences
Broadly speaking, the mammalian immune system is split into two branches: innate and adaptive. The innate immune system is what’s left over from earlier stages in our evolution and is basically a way of making ourselves a tough place for pathogens to survive. This is done in a number of ways of varying sophistication. One simple mechanism is inflammation at an area of infection. In inflammation, innate immune cells (a branch of white blood cells known as non-lymphocytic leukocytes) such as macrophages or dendritic cells detect fragments of pathogens that are common for many species, things like components of the bacterial cell wall or particles of viral DNA. This detection is achieved by receptors present at the surface and in the interior of these cells that have developed alongside pathogens throughout our evolutionary history and so are well-tuned to detect them. The activation of these receptors by pathogenic components causes the cells to release a whole host of pro-inflammatory molecules - one well-known example is histamine, which causes vasodilation and hence inflammation, and is why you will have probably taken anti-histamines if you suffer from allergies.
Other aspects of the innate immune system are somewhat more sophisticated as they either actively destroy pathogens or ‘opsonise’ them, which is a way of flagging them up to the rest of the immune system. The complement system is a good example of both of these as it is a collection of proteins that float around in the blood and bind to specific common pathogenic components on invading bugs. These can then either directly damage the pathogen, as in the case of the well-named ‘membrane attack complex’ or act as signals to other immune cells to destroy the pathogen, such as with the ‘classical’ complement pathway.
The adaptive immune system - the sharpshooter of immunity
That’s all very impressive but a little, let’s say, unevolved for us. Don’t get me wrong, the innate immune system is important and without it you would be in some discomfort from warts, parasites and the like, but you’d most likely still be alive. It’s also very important in the early stages of your life, as in early infancy the other ‘adaptive’ branch of the immune system is still developing. However, when it really comes to sophisticated defence against disease, the adaptive immune system is where the real effects are seen.
The adaptive immune system is, as you might expect, adaptive. While the innate system relies on bits of pathogens that are common to many species, the adaptive immune system is able to pick details on individual pathogens and launch attacks specifically against that bug. This has the advantage of allowing a finely-tuned response to infection that is not only more effective at clearing the pathogen, but also does so without the collateral damage that comes hand in hand with mechanisms such as inflammation. This system is reserved only for higher organisms as it originally began to arise in jawed vertebrates about 450 million years ago, and the mammalian system that we enjoy is pretty much as good as it gets! The fact that we’re not all dead or dying is primarily down to the adaptive immune system, and those unfortunate enough to be born without it usually don’t live to see their first birthday despite modern medical intervention.
So how does this amazing system work? Well, what makes the adaptive immune system adaptive is a group of receptors that are expressed on the surface of the adaptive immune cells (called ‘lymphocytes'). Lymphocytes are, broadly speaking, either T or B cells - in future posts I will go into more detail about how these two cell types cooperate to generate an immune response, but for now just knowing their names is enough. Every B cell in your body expresses a different B cell receptor (BCR) at its surface, and every T cell, surprise, surprise, has its own T cell receptor (TCR). Each BCR or TCR has a different structure and so is able to recognise a different set of components, which are generally referred to as ‘antigens’, and can be anything from proteins to DNA to carbohydrates. These antigens may be from pathogens, they may be from your own body, or they may not exist anywhere in nature because TCRs and BCR are not designed with anything specific in mind, they are generated at random in the hope that they will recognise something useful on the surface of a pathogen.
This process of TCR and BCR design occurs early on in the life of a T or B cell, when it is developing in either the thymus or bone marrow (hence T and B). The genes responsible for encoding the TCR or BCR are chopped up and stuck back together at random (a process known as VDJ recombination) while little random inserts are sometimes stuck in for fun. If, as is the case for most combinations, the way that the genes have been stuck together does not make a functional protein, then the process is repeated until it does. Once the cell has a TCR or BCR that is able to get to the cell surface in tact, the cell undergoes a series of selection mechanisms that cause any cell whose receptor recognises antigens from your own body (so-called ‘self’ antigens) to kill itself, which is about 99% of them! The 1% or so that get through are sent to adaptive immune centres, such as lymph nodes, where they will wait for an opportunity to protect you against infection.
In my next featured post I will be talking about how T and B cells work once their TCR or BCR recognises antigen from a pathogen, and how the whole system is interconnected and interwoven to give an effective, rapid and long-lasting response. Later in this series of posts I will present some of the important questions that we have about how this system works and what is being done to answer these questions.
The next post in this series is found here.
The next post in this series is found here.
(Photo is a scanning electron microscope image of two macrophages - rights belong to Steve Gschmeissner and the Science Photo Library)