COVID-19 Blog Series: Part 1

Fighting back: The immune system’s battle against COVID-19 

SARS-CoV-2 is the virus which causes COVID-19, a disease which I’m sure you’ll all be familiar with by now. It has tragically caused the deaths of over a million people worldwide – but not everyone who catches it gets severely ill. What is going on in the individuals who suffer from COVID-19 the most severely? The secret lies in their immune systems. 

The difficult thing our body must deal with when fighting COVID-19 is that the virus likes to hide inside our cells. Here, the virus is shielded from detection and attack by our immune system and can happily replicate itself to produce more virus. Fortunately for us, when a virus like SARS-CoV-2 invades a cell, it causes a change on the cell surface, a change that allows our immune system to notice the invaded cell is different from all the others and has a virus inside. This triggers an immune response to clear out all our cells which have become infected. 

Our immune response to a virus is split into two main sections: the innate immune response and the adaptive immune response. You can imagine them like two teams which work together to fight an infection. The innate response is the first team to jump in when we detect a virus. Immune cells that are a part of this team are on site very quickly and deploy numerous techniques to try and combat the threat straight away.  

Macrophages are a type of cell in the innate immune response. They are famous for their ability to engulf pathogens whole and ‘eat’ them, but they are also really good at sniffing out which of our cells are infected with the virus. They can use their ability to ‘eat’ to destroy virus parts or even eat up infected cells whole. Being one of the first types of immune cells on the scene, macrophages have a really helpful ability to release chemical signals known as cytokines into the surrounding area which can recruit other immune cells to the site to help battle the virus. These cytokines are particularly useful in boosting the responses of T cells, which you’ll hear about further down! Usually this is a beneficial trait of macrophages, but it can actually cause problems in an infection with SARS-CoV-2. Scientists have found that in some COVID-19 patients who have very severe symptoms, their macrophages are over-activated and are producing far too many cytokines. The big excess of cytokines means that loads of immune cells are recruited into the area and a lot of inflammation occurs which can be very dangerous, especially when this happens in the lungs. But why are these macrophages so hyperactive in COVID-19? Well, we’re not sure yet. It’s thought that perhaps when the virus infects our cells it can cause them to produce cytokines of their own. These in turn can act on macrophages to trigger their activation, causing them to pump out a load of their cytokines too and cause inflammation and the recruitment of other immune cells to the area. Investigation into what is going on with macrophages in COVID-19 is still ongoing, but there’s a real focus on this cell type in COVID-19 research, as they seem to have a substantial role to play in the disease. 

A while after the innate immune response has had chance to do its work, the adaptive immune response kicks in. This response is more specific to the virus and has a much more targeted approach to fighting it.  

The immune response against SARS-CoV-2: At the site of infection, in the lungs we see activation of macrophages (Mac) as well as neutrophils (Neu) which release inflammatory cytokines and engulf viruses. Killer T cells help by killing infected cells to help limit infection. Dendritic cells (DCs) carry bits of virus to the lymph node (you’ll feel these as swollen ‘glands’ when you are ill!) where lots of immune cells meet up. Here DCs show the T cells what they found – activating them, and T cells can help B cells. B cells can then become plasma cells that make antibodies which can neutralise virus to prevent infection. B and T cells can become memory versions of themselves (memory B cells and memory T cells) which respond more rapidly and effectively next time they see the virus! 

One type of cell in the adaptive immune response which you might have heard about on the news recently are T cells. T cells come in two ‘flavours’, the ‘all guns blazing’ killer T cells and the appropriately named helper T cells. Killer T Cells, unsurprisingly, kill infected cells which helps to limit infections and helper T Cells send out messages in the form of cytokines to help tell other immune cells what kind of threat they are dealing with and how to tackle it! Unlike the innate cells, T cells have a special receptor, which is basically randomised. When a T cell comes along with a receptor that can recognise specific bits of SARS-CoV-2, it will be able to multiply and so we end up with more T Cells that recognise this virus. After a first encounter with these ‘bits’ of virus some T cells will become ‘memory’ T cells, which stick around for longer and when they see the virus again can rapidly multiply – importantly this means they can protect us from COVID-19 disease in the future.   

So, what do we know about T Cells in COVID-19?  

Well, when they are doing their jobs correctly it seems they help to protect us from severe disease and control the infection once it has started 1,2,3 . cells can recognise different bits from inside the virus – which are more stable and less likely to mutate than some of those on the virus’ surface. This could make them important for protection from new variants that have changed their spike protein4, a part on the outside surface of the virus.  Killer T cell memory after infection lasted a similar time to what we see from the yellow fever vaccine – which is designed to give immune memory, so that’s great! And the helper cell memory lasted a long time too, especially the T cells that help B Cells to make good antibodies (which you can read more about in the next section). T cell memory was seen in between 50-92% of people in this study 6 months after infection – depending on the type of T cell 5. So, if T Cells help prevent severe disease why do we still see some people get so unwell? We know that older people tend to have more severe disease and do less well, and a link between a poor T cell response has been suggested as a factor1 since as we age, the source of our new T Cells, the thymus gland shrinks. Without these new ‘naive’ T Cells it is more difficult to generate T cell responses to new viruses, like SARS-CoV2. 

So T Cells are important to stop us getting too ill in a COVID infection- but how about stopping the virus getting into our cells? Next, we will talk about B Cells that can help us do just that! 

Like T cells, B cells are critical components of the adaptive immune system. There are more B-cells within an individual’s body (~10 billion) than there are human beings on earth and their contribution towards our immune system underlies virtually all successful vaccination strategies. When B-cells recognise SARS-CoV-2 they require signals from helper T-cells in order to replicate and produce an army of B-cells which possess receptors capable of recognising the virus. Similar to macrophages, B-cells can produce cytokines which will boost T cell responses in the area. A proportion of these B-cells will develop into a cell type known as plasma cells, which produce proteins called antibodies that will bind to and ‘neutralise’ the virus by trapping SARS CoV-2 in clumps, thereby preventing them from interacting with and infecting host cells. These antibodies can persist within the bloodstream for several months following initial infection – we can do tests to detect these antibodies to work out whether an individual has previously been infected with SARS CoV-2. People who have recovered from the virus are being asked to donate blood plasma, which will likely contain these anti-SARS CoV-2 antibodies, to help treat those critically infected. 

Understanding the immune response to SARS-CoV2 is a vital part of the fight against COVID-19. Make sure to check out our next blog in this series to see how training our immune system with vaccines can help!