We have all had to learn a lot of new words in the last 6 months. Furlough anyone? Although I was aware of the medical terminology, the specifics of some of it are something I’ve had to brush up on. Some words and phrases are being used to tell us why we need to behave in a certain way, so I think it makes sense to ensure we understand the information being thrown at us. We can thus adapt to the ‘new normal’ (another phrase that has gained popularity of late) in a responsible and informed manner. So let’s take a walk along the pathway to immunity, meeting antigens, antibodies, cellular immunity, and asymptomatic carriers.
The processes involved in our defence from things that would harm our bodies (infectious agents and our own cells gone wrong) are complex, adaptable, and in my opinion pretty amazing. The first line of defense is the skin, or the equivalent internally (endothelium – lining of the nose/lung tubes/gut etc). Bacteria for example may live harmlessly on the outside of this barrier (the gut ‘good bacteria’, and skin ‘flora’), and it is only when they breach it that they may cause problems. However, they’ll have to fight a war against our immune system first. When they breach the initial barrier, they are met by our innate immune system. Cells just inside the skin/endothelium detect proteins/other molecules from the invading bacterium/virus/parasite (pathogen). The proteins/molecules that our immune system detects are called antigens. It is these that the nose and throat swabs for SARS-CoV-2 (the virus causing covid 19) look for, hence being called antigen tests. They can only detect the antigen if there is enough of it, so if the swab isn’t collected properly, or there aren’t many copies of the virus (virions) present at that moment, then the test won’t be able to detect the antigen. That’s why the most sensitive time to take the antigen swab is days 2 to 5 from becoming infected – on day 1 there may not be many virions around yet, but after day 5 the immune system should have killed lots off, so again, not many around. The government website says it a different way: antigen testing is most effective within the first 3 days of symptoms. Symptoms generally won’t develop the moment someone becomes infected, because both cell damage and immune reaction (which cause the symptoms) take a bit of time to climb to levels where we become aware of them.
For some people, with some pathogens, the pathogen can be there, but their immune system holds it in check sufficiently well that they get no symptoms (are asymptomatic). It appears from research to date that SARS-CoV-2 is not infrequently present without causing symptoms, although some people are actually pre-symptomatic rather than truly asymptomatic – they go on to get symptoms later. The word carrier is used to mean someone infected with a pathogen (or having a harmful gene), but who shows no signs of harm from it. A carrier can however pass the pathogen (or gene) onto someone else. An important question from a public health perspective is whether SARS-CoV-2 can spread from asymptomatic carriers to others. The research to date suggests it can, which explains the sense in generally trying not to get too close to too many people even if you feel fine, just in case you’re one of the carriers. It isn’t harming you, but it could harm your friend or relative if they get it from you.
For the innate immune system the antigens detected only need to be similar to those of other pathogens to trigger a response. So even if our immune system has never met that particular pathogen before, it responds and starts to fight it off. The cells just inside the skin/endothelium engulf and destroy the pathogen (using toxic chemicals kept safely in granules within the cell until they are needed). They then release other chemicals which increase blood flow to the area, activate pain receptors, and attract other blood cells to help destroy pathogens (the area gets red, hot and painful). At the same time chemicals in the blood detect the pathogen and set off the ‘complement cascade’, a series of enzyme reactions ending up with a complex of proteins able to punch holes in the cells of the invading pathogen! Some pathogens try to sneak past the innate immune response by hiding inside our own cells (viruses are one of these, and they even cheekily use the cell’s own energy/enzymes to replicate themselves). But our innate immune system has a back-up plan, with infected cells releasing chemicals (called interferons), which trigger neighbouring cells to check if they have also been infected, and if they have to self-destruct (apoptosis) before the virus can start to replicate itself. Uninfected neighbouring cells increase surveillance for invading virions, and slow down their own protein production, so that if they do get infected then viral reproduction will also be slower. I find that all pretty incredible, but that isn’t even nearly the end of the journey to immunity.
The adaptive immune response kicks in next, and is about making cells and proteins (called immunoglobulins, or antibodies) which recognise specific antigens, and thus specific pathogens. Some of the cells that engulfed and destroyed the pathogen initially also have the function of ‘presenting’ the antigens from the pathogen. This means they head to the lymph glands, and sit antigens on special protein complexes on their surfaces, where passing white blood cells, called T-cells and B-cells, can ‘see’ them. When a T-cell binds to the antigen which matches the combination of proteins it has on it’s surface, it becomes activated. Depending on the exact type of T-cell it either goes off to kill viral infected cells, or to produce chemical messengers (cytokines), which are toxic to infected cells, and also spur on other aspects of the immune response. If a B-cell finds it’s matching antigen it too becomes activated, and, assisted by cytokines from the T-cells, it clones itself many times, and starts to produce antibodies. These are proteins shaped exactly right to bind to the antigen which activated the initial B-cell, and they go off in the bloodstream to do that. Antibodies bind to their specific antigen on the pathogen, stopping it from entering our cells, or killing it directly by disrupting other important functions. They also mark it out as a target for the various killer cells.
This process takes a bit of time, so the body has developed a short-cut to speed things up if there is an attack by the same pathogen in the future. A few of the T and B-cells become memory cells, which wait in the lymph glands long after the antibodies and killer cells have gone. If the pathogen invades again these cells respond much more rapidly to mount a response. That is what is meant by the press by cellular immunity – these memory cells, which are not detected on antibody blood tests, but are waiting to mount an immune response if the pathogen returns. There is no test for cellular immunity to SARS-CoV-2, so it is difficult to study whether people infected with it develop this type of immunity. Or indeed how long it lasts if they do. We know that the antibodies (which our current test detects) don’t last long in the bloodstream for most people (weeks to months), but there could be a memory B-cell sat waiting to produce them again should the virus invade again. But we don’t know.
What we do know is that face masks (no matter how horrible to wear, particularly for 11 hour shifts) are effective at controlling spread. We know that washing hands, wiping surfaces, and keeping a safe distance from each other reduces infection transmission. And we know that we want our immune system to be in top condition when we meet a pathogen, particularly this one with seriously limited treatment options, and no man-made shortcut to immunity (vaccination).
Next post I’ll share what I’ve found out about how to keep our immune systems in best fighting condition.
By Dr Kate Roberts-Lewis
The opinions expressed in this blog are those of the authors and not not necessarily those of DHU.