Our amazing immune system

(On this page in Dutch I post daily bits of realistic but hopeful Corona news. Here is a somehat rough translation of an article on our immune system I posted there, because I think it might also be useful for people that don’t speak Dutch).

Wednesday, April 1st

COVID-19 can only live thanks to us. Viruses cannot reproduce independently, they need our help. And our immune system makes this very hard, as aptly explained in this excellent xkcd comic:

Before we continue, it is good to realize that our immune system appears to be >99% effective against COVID-19, perhaps 99.9%: “three nines” as we call it on the internet. It could be even better, we don’t know how many people just never got sick at all because their immune system was there in time. Hopefully the RIVM (Dutch CDC) “PIENTER” research and the tests at Sanquin (the Dutch blood bank) will tell us this soon.

Note: although I know a lot about DNA, the immune system is also new to me. Normally I don’t write about topics that I don’t understand very well, but these are execeptional times. If you are an expert or know one, can you ask them to read this article critically and tell me what’s wrong at bert@hubertnet.nl? Then I can quickly fix any errors. I am also aware that I have skipped over many nuances in my description, but I am most concerned with whether there are concrete untruths in what follows. Thanks!

Imagine a flashy spaceship lands in your backyard. The door opens and you are invited to investigate everything to see what you can learn. The technology is clearly millions of years beyond what we can make.

This is biology. That’s why it fascinates me so much. Life is billions of years old technology, and we can explore it to see how it works!

Almost everything that we as humans have ever thought of existed in nature for millions of years already: information storage, complete chemical factories, signal processing, image processing, measurement and control technology, artificial intelligence (but then the real thing). And invariably we discover that the technology of nature is many times more powerful than what we ever invented as humans.

To give a concrete example, even in 2020 we are unable to recognize proteins quickly with technology that we have invented ‘as humans’. To do so, we put the protein in a rabbit, wait a while, and then we use the antibodies that the bunny made for us. We can then make tests for that protein with those rabbit antibodies. We can’t get there without nature’s help.

Our immune system is really unbelievably clever and far beyond anything we can do with human hands. Unfortunately, we do not receive reports from our defenses “Last month 100.0% of all bacteria and viruses were kept out!” We should maybe appreciate it a bit more.

So why does it sometimes go wrong? Unfortunately, it seems that our immune system occasionally goes off target and is overly active in the wrong place. There are drugs that can dampen that, and much hope rests in those medicines to cure seriously ill COVID-19 patients.

A few months ago, or as it feels, thousand of years ago, we thought that bacterial anti-biotic resistance was the biggest threat to our health. Bacteria evolve so fast, developing medicines seems hopeless.

But as it turns out, human beings have similarly powerful resistance mechanisms - for every communicable disease that comes along, we develop resistance in a week or two. And often subsequently remain immune throughout our lives.

How do we do that? Bacteria evolve directly, but it turns out that our body has its own evolution laboratory. The idea is as simple as it is brilliant. In a previous Corona Update, I described how antibodies “stick” to antigens (such as virus components). After sticking, the virus is either disabled immediately or auxiliary troops arrive which then destroy the virus.

In our body, antibody factories circulate, created randomly before we were born. The antibodies produced have been filtered to not stick to ourselves, but there is a good chance they will stick at least somewhat to everything else.

Each antibody is made by its own factory, the so-called B cells, also known as white blood cells. Each B cell only makes 1 type of antibody.

As soon as our body detects it is being damaged, and an infection is apparently going on, our immune system goes into top gear. And now comes the smart bit. DNA can be called “the source code of life” without exaggeration. (I was fortunate enough to present about this at SHA-2017 for two hours, video & slides )

Each B cell makes only 1 type of antibody, and the description of that antibody is contained in the DNA of that B cell. Note that normally all our cells have the same DNA, but B cells are allowed to change their genome. And this turns out to be a good idea.

The DNA source code of the antibody in the B-cell is used twice:

1. To make antibodies for export to the blood, to kill viruses etc.
2. To attach antibodies to the outside of the B-cell (the factory)

And here’s how it works. A new virus, say COVID-19, circulates in our body and causes damage. Our body fires up the immune system, but there is still nothing specific to attack COVID-19. But due to the overwhelming amount of random antibody designs generated earlier, there is probably one that one will stick to the virus, if only a little bit.

Sometimes COVID-19 will now get stuck on a B-cell, because it also has antibodies on its outside. Apparently there is a (weak) match between this antibody and the virus. The B cell senses that it is “occupied” and then receives the command: CLONE AND MUTATE.

Normally, our body makes virtually no mistakes when copying DNA, but B-cells are an exception to that rule: the DNA for the antibody gets copied with an error rate up to 1 million times higher than normal. In addition, this DNA is also creatively scrambled, rearranged, many things are possible.

The “occupied B-cell” now clones itself, but the offspring is different from the original. Maybe the antibody works a little bit better now, but often it will be worse.

If it is an improvement, the copy will have a greater chance of sticking to a COVID-19 particle again. And this improved copy now restarts the process: DIVIDE AND MUTATE. And so on, and so on.

In this way, within a few days a B-cell evolves which is a factory for antibodies that fit the virus perfectly. And because these well-functioning B-cells are allowed to continue to copy, a strong flow of antibodies is instigated.

These B-cells then remain active for as long as necessary, but over time they ‘fall asleep’, ready to fight a new infection quickly should it come back. This is then our long-term immunity.

The central trick that the B-cell antibody factories themselves also cling to the virus, and thus get the command to mutate and share, is really unbelievably clever.

No matter how dark things seem now - our immune system is incredibly effective. With any luck, we will quickly find treatments for those tragic cases where our immune system was not fast or good enough.

Please stay tuned for further updates!