If you are old enough to remember London’s Burning (if not, it’s still shown on the Drama channel) you will recall that each programme would build toward the main event – a fire that was the culmination of every episode. Despite the show being about a single theme – fire – you never knew just what kind of fire it would be until the first engine on the scene radioed back to the control room with the initial assessment, hence the title above. It is also a rather good metaphor to describe the power of your immune system.
The immune system is our built-in biological defence system, an intricate ecosystem of organs, cells and proteins that exist solely to protect the body. In simple terms, it consists of two parts: the innate and the acquired or adaptive.
You are born with your innate immune system and it is always on, 24/7. Cells called immature dendritic cells are constantly on the lookout for invasive microbes, such as those of a virion, using pattern recognition to identify pattern associated molecular patterns. When they detect a pattern that suggests all is not good (their pattern recognition is particularly adept at spotting nucleic acids, present in viral RNA or DNA sequences), they ‘break glass’ and the fire alarm goes off. Proteins called cytokines are released that mark the target and dial 999,
Dendritic cells have limited fire-fighting capacity themselves but like the extinguisher on the wall or a sprinkler system, they have a go at attacking the fire as best they can, using a process known as phagocytosis. This is where a host cell engulfs an invasive microbe, breaks it down and destroys it. As soon as they go from patrol mode to active mode, dendritic cells change from immature to mature. They then leave the scene of the fire and head off toward either a lymph node or the spleen. There, they become antigen presenting cells, presenting the control room with information on just what it’s up against, in the form of the bits left over – the antigens – from what they engulfed at the site of the fire.
While this is going on, back at the fire, fire-fighting cells that were in the area are piling in, with a whole range of cells including mast cells, macrophages and neutrophils all attacking the pathogen. Natural killer cells also turn up, targeting host cells that have been infected. This process is self-reinforcing as certain cells release chemokines, which are essentially invitations to more of their friends to come join the party.
Not wanting to be left out, the complement system lends a hand, effectively turning up with one of those high volume pumps that can make sure as much water can be directed at the base of the fire as quickly as possible. In addition to inflammation* and phagocytosis, the complement system also attempts to poke holes in the pathogen cells, through something called membrane attack complex.
*When an insect bite or sting swells up & goes red really quickly, that is the innate immune system cordoning off the area and sending in neutrophils to act as the rapid response team. The pain component of inflammation (the others being heat, redness and swelling) is actually the sensation of neutrophils and other cells flooding to the site and beginning to go to work, with the redness component down to mast cells releasing histamine to dilate the local blood vessels.
This whole process goes on for up to 3-4 days. The response is the same regardless of the pathogen as the innate immune system isn’t antigen-specific. This doesn’t mean that is can’t destroy specific antigens – it depends upon many factors, including in the case of SARS-CoV-2 the viral dose. At low viral dose, the innate system is more than capable of taking it on and overcoming it without the help of the adaptive immune system. This is why many people can have SARS-CoV-2 without knowing or with mild symptoms.
It is no coincidence that after a similar period of 3-4 days, the adaptive immune system starts to activate. Unlike the innate system, the adaptive system is normally dormant. Once activated, it tells the innate immune system to prepare to stand down, as it is ready to take it from here.
It is equally no coincidence that SARS-CoV-2’s reaches peak viremia just before the adaptive immune system starts to get going and the infection cycle is firmly on the wane when the system kicks in fully.
Remember those now-mature dendritic cells that turned up at lymph nodes and the spleen, carrying bits of antigen? They have been joined by other antigen presenting cells, in order to give the control room as much detail as possible: multiple 999-calls have been received and the first unit has radioed in from the scene. Knowing what it needs to fight this particular fire – the antigen – the adaptive immune system now starts to issue orders to white blood cells called lymphocytes.
There are two main types of lymphocytes; B and T cells: B cells are tasked with the humoral response, which is dealing with antigens circulating in the body but outside of cells. Think of the flames and embers you see coming out of a burning building. To do this, B cells release antibodies, which hunt down antigens and deactivate them (antibody cancels out antigen). T cells are tasked with the cellular response, which is dealing with infected cells. Think of the fire inside of a burning building.
Some of these T cells have been active at the site of the fire so already know what they are dealing with but others don’t: these are raw or naïve T cells and these coded with the blueprint of the antigen. This programming effectively activates them as well as provides them with their specific target. the adaptive immune system is very specific in the details it gives to B and T cells: they are programmed to recognise ‘non-self’ and differentiate it from ‘self’ to remove the risk of attacking healthy host cells. What’s more, lymphocytes are also instructed to replicate themselves when they encounter an antigen, something called clonal selection. This means that there is an increasing number of lymphocytes, each new one a clone of its progenitor and armed with the same instructions.
The main T cells are effector or cytotoxic, meaning they are toxic to other cells, destroying them by breaching their membrane in a process called lysis, In addition you have helper T cells and regulatory T cells that manage the adaptive response and aim to make it as efficient as possible. There are even hunter killer T cells, which use a different method of detecting the antigen to cytotoxic T cells but are equally effective.
On top of this, the immune system checks its records to see if it has encountered this antigen before: if so there will be memory T cells present in the body. These are effector T cells that are survivors from previous missions, kept on just in case they were ever needed again. Memory T cells can hang around for several years (memory B cells for decades and memory cells are closely related to vaccines), as when the adaptive immune response is drawing to a close and the pumps on scene are damping down, it embarks on immunological memory: this is telling the diseased/dead cell-eating phagocytes to leave some now-redundant B and T cells alone when they are cleaning out the system post-infection.
This incredibly condensed and simplified introduction to the immune system outlines just how fantastic it is, as well as how complex and efficient. It is the product of millions of years of evolution. It is not invincible – far from it – but it is also very resilient in the face of most pathogens.
The most effective, powerful and best defence against any infection in general and SARS-CoV-2 in particular is you. You and your pretty amazing immune system.