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Brave cells in the lung: the invisible enemy

What happens inside of your body when you meet a new virus? One you have never seen before. This is a story that helps you to understand how your immune cells fight new viruses.

I live in your lungs, deep down inside of you.

Can you see me or feel me?

Unfortunately, I don’t think you can. I’m so small and hidden from you that you don’t notice me.

But I have so much to tell you.

I’m not alone down here, we are many. Many, many cells. We are all immune cells, a close family of cells working together to help you stay healthy and fight off any invader- everyday of your life.

Our world is invisible to the bare eye and you can only get a glimpse of what we look like when you take a magnifying glass. And even if you’d look at us with a very powerful magnifying glass you probably wouldn’t understand how we live.

To find out, you would have to be here with us. See what we see, feel what we feel.

Do you want to find out? I can show you.

But it’s quite a journey to get to us.

First you have to crawl up your nose. I hope you don’t have a lot of snot sitting there right now. That makes travel difficult. Well I guess that’s one of the purposes of snot anyway.

Inside your nose you see multiple rooms. Keep going straight to the opening at the very end of them. This is your windpipe.

Come a bit closer to the opening. Now you have to jump down. One…two…three. Jump!

Whoops.

I suppose you’re stuck now somewhere in your windpipe. It might sound odd, but that’s actually OK. We are heading to your lungs. They have many ways to protect your body, so that you can’t pass when you’re too big- which you clearly are.

The strong muscles around the windpipe will squeeze tight and throw you out again by coughing.

Since you want to meet me in the lungs you should make yourself a lot smaller now.

There you go!

Now you’ll manage to get deeper and deeper down this pipe. At one point it will branch off into a left and a right tunnel. Go left.

Now the tubes get smaller and start to branch off here and there. Because it’s quite a maze I want you to keep going straight until you can’t anymore and then always turn left so, you don’t get lost.

As the tubes narrow you need to shrink even more.

Can you see the hair on the walls here? There’s also a sticky, slimy coating on this hair. Make sure you don’t get stuck in this. It works like a spider web. Don’t touch it, otherwise you’ll get stuck.

The hair will then gradually move you outside again. Which means we’ll have to start from the beginning again.

But don’t worry. I’m guiding you and you are really small.

Keep going a bit further. Now you are finally at your destination.

This is a very, very narrow pipe. The smallest one of all the ones you have passed so far. It ends here and gives way to a small round room.

This room is called an alveole, it looks like a bubble. The walls of this room are built in such a way that oxygen from the air can pass through and carbon dioxide leaves in return.

Rooms like these are the essence of life. They let you breath.

Now you understand why they are so hidden and well protected. Have a close look at the walls of this room.

It looks like cobblestones, right? Do you also see the tiny hairs on each cobble? The cobblestones are the guardian’s heads, and this is their hair.

They are standing so close, shoulder to shoulder, that you can’t tell where one starts and the other stops.

Tell them that you know me and that I invited you in. Only then, will they let you pass.

This is where your world ends and ours begins.

Illustrations: DIDI (scientific name: Dendritic Cell; from dendrite- branching, tree-like); THE GUARDIANS (scientific name: epithelial cell); NAHLA (scientific name: Natural Killer Cell; the name says it all)

Hello, nice to meet you.

I am Didi, an immune cell in your lung.

I live here, below the guardians.

We talk to each other by sending us floating messages. However, there are some words I can’t understand. Just like reading words from a different language, I then have to ask the guardians to translate for me. I come here often, to hear about the latest news about what is happening outside.

Besides your arrival, nothing much has happened today. But it wasn’t always like that.

Gee, a couple years ago when you were born, we – your immune cells- went through turbulent times. They went on for a while. Everything was new to us. We had to learn so much, very often the hard way.

Oh, I remember these times as if it was yesterday.

One day- it was a nice calm day- I was chatting with one of the guardians. Suddenly, I heard a loud cry in the distance.

But I didn’t know where it was coming from.

Frantically, I looked right and left, trying to locate where the cry was coming from when all of the sudden, I saw a floating message. Soon there were more and more of these messages appearing. Following their source, I finally found a guardian behaving really strangely. “What is wrong with you?” I asked him. Agitated and out of breath, I didn’t even give him time to answer. “What happened? Tell me!” “Nothing. Argh…” he looked completely normal but then he flinched, and his eyes suddenly rolled back, so that only the while of his eyes showed.

It was really scary. I have never seen anything like that before. “Something is inside of me.” he howled, all of the sudden twisting with pain. “Inside?” I was confused.

His eyes came back, but had this intense stare to it, like he was obsessed. Initially, when I saw his floating messages, I thought something was invading us again.

In the last weeks and months, we had several break-ins. I vividly remembered the cute-looking furry bacterium who snuck in secretively and the mean fungus who viciously attacked the guardians with its thin tube-like fingers. But this time, the situation was different. Whereas the bacterium and the fungus were clearly visible, now I couldn’t see a thing.

But something was clearly not right with this guardian. Hesitant at first, I slowly got a bit closer to him. He was still staring to some place in the distance. His intense gaze followed me when I moved, but he didn’t even blink for a second. “What is the matter with you?” I kept repeating, aware of how helpless I must sound. Suddenly, in a blink of an eye, his neighbors also rolled their eyes back and then screamed from pain. Like a domino effect from falling tiles, one guardian after the other, was affected. Whatever it was, it was spreading from one to another. At this very moment my sister Nahla appeared. She also had picked up the guardian’s floating messages. She looked deeply concerned. As soon as she arrived, she asked me to hold one of the guardians tightly, so that she could investigate him thoroughly. “This is suspicious,” she then proclaimed, “normally I can see on the outside what’s inside of them.” She looked him deeply in the eyes. “Then there is this empty stare in his eyes. He’s hiding something.” “We need to do something” I yelled at her. Her voice made me antsy. “They are obsessed.” she mumbled, more to herself than to me. “They must be infected with a virus. It is hiding inside of them and is taking control over them. They can’t even tell us what’s wrong anymore.” “I don’t really have time for this” I grumbled, not knowing what to do with all of this information. But then Nahla took out her slingshot and bags full of poison marbles. Nahla is a very skilled fighter, I’ve seen her train before, but I have never witnessed her in action. “What...?” I started, but Nahla already took aim and was firing at the guardians with her poison marbles. I was shocked. She was killing them! “This is the only way.” She shouted at me, as if she had read my thoughts. “They will be miserably dying from the virus. We have to kill them faster, so they are not in pain.” A marble hit him hard. “This will stop the virus from spreading to the next one.” The poor guardians were screaming and trying to escape. But they couldn’t move because they were standing so close to each other. “The virus uses the guardian’s own body to make more viruses” Nahla screamed amidst the guardian’s cries. I was so upset. It was hard to look at. The obsessed guardians who had been hit hard by Nahla’s poison marbles, started to collapse. Their neighbors now couldn’t hold on to each other anymore. Where there used to be a strong wall of guardians, there were now gaps. The fluid that normally flows in between all of us started to leak out. Confused, I stood there watching how some guardians got swept away by the flood that started. Meanwhile Nahla was killing one guardian after the other. This was a bizarre scene and it took me minutes to snap out of it and take action. I quickly scanned the row of guardians to figure out who was already infected and who might still be healthy.

There seemed to be a pattern. I rushed to the guardians who I thought weren’t infected yet. “Stop whatever you are doing now. Go into stand-by mode, so that when the virus infects you it won’t be able to use your own body to make new viruses.” I told them. The guardians were all screaming.

They were horrified.

It wasn’t easy to get their attention. I kept repeating and repeating this, until one guardian finally listened. “You think this could work?” he asked, turning to me. “Yes!” I shouted back. “I will tell the others.” the guardian declared and instantly released floating messages with the instructions for his neighbors.

The guardians were also sending out lots and lots of floating messages calling my family for help. The situation was so dire right now that I was happy about any help. How can it enter the guardian’s bodies? And how could we possibly know which guardian is infected already? We needed the help of an expert- somebody who knew about this virus. How could I find this expert? How could I even explain the problem? It dawned on me that there was no other way.

I had to catch one of the viruses. But how could I do that when I couldn’t even see it? “I can try to catch one the moment it spreads from one guardian to the next.” I thought to myself. Not knowing if or how this could work I squeezed next to the guardian who had just warned all of his neighbors to go into stand-by.

I poked my arms in between him and his immediate neighbor and waited. “Would I feel something the moment the viruses pass by?” I wondered. Then suddenly I felt them.

They touched my fingers and like a sort of magnet they stuck to them. Instantly, I pulled them closer to my body and swallowed them. Inside of my body I kept them tiny cages, so that they couldn’t infect me. Now I needed to hurry to get help and find an expert. I knew that my best chance to find one would be in our nearby houses. So, I squeezed through the tunnels which connect the lung to our numerous local houses.

Illustrations: TESS (scientific name: Effector or Cytotoxic T cell; A T cell that can kill other cells: cyto- cell toxic- poisonous); TAMARA (scientific name: Helper T cell; A T cell that helps other cells); BEN (scientific name: B cell; B as Bone Marrow- the place the cell is born)

“Do you know this virus? Can you help me?” I shouted when I arrived at the first house.

It seemed hopeless. Nobody I met seemed to be able to help me. “How is this possible?” after having passed several houses with no luck, I was desperate.

By then the news of the virus had spread everywhere through floating messages and everybody I met along the way, told me that they wanted to help.

That was very nice of them, but I needed to find someone with the key to this virus. I was afraid that more help without the expertise on this virus wouldn’t get the situation under control.

Then finally, it felt like hours later, I met my sister Tess.

“I’m looking for somebody who knows more about this virus” I told her showing her the virus in the cage. “Look closely! We’re…invaded ... at the lungs. The guardians are dying.” I babbled out words, too worried and anxious to form a proper sentence.

“The virus is spreading. Help!” I almost shouted.

But Tess didn’t pay attention to me.

She only looked at the virus. “That looks like…wait…I might know what this is…It’s…” she paused, picked it up and looked at it up closely.

“You know what it is?” I asked.

But this was taking too long. “We need to be fast. The guardians…! They’re dying! Tess!” I bawled while jumping up and down, “Tess…!?”

What was she doing?

A second ago there was only one Tess in front of me. Now I could see three –wait- four, five of her. Tess seemed to copy herself within seconds. More and more of her were appearing.

“Go and find Ben and show him the virus.” One of her copies told me. I marveled at the sight of Tess copying herself right in front of me, but a second later they already disappeared into the tunnels, rushing to get to the lungs as fast as they could.

Since Tess (or one of here copies) had told me to look for Ben, I set out to find my brother.

After a seemingly endless journey through yet more houses, I finally found him. And oh, was I relieved when he also recognized the virus. I told Ben everything I knew.

He just stood there and listened carefully. The longer I was talking the more concerned he looked.

“If this is true what you tell me we need to get Tamara’s help.” He said with a troubled look on his face.

“Tamara?” I was confused. I spent so much time trying to find Ben. Imagining the situation back home in the lungs and how much time had already passed while searching for him, I wasn’t sure that we should also look for Tamara now.

But I trusted him and we both went looking for her.

It felt like an eternity but eventually we found her. While Ben was holding up the virus in its cage, she came closer to have a better look. And indeed, she recognized it as well.

Both of them were putting their heads together for a long time and I heard them nervously debating about the design of a missile.

When they were finally done, Ben turned to me and showed me the missile they made.

“This is a sticky dart. Once it hits its target it sticks to it.”

“How?” I wanted to know.

“Tamara and I designed it in such a way that it should stick to the virus you showed us. Once many darts attach to this virus it becomes so bulky that it can’t get a hold of the guardians anymore.”

He explained. I was amazed. It would be fantastic if this could work.

By then Ben had also multiplied into hundreds if not more, copies of himself. “The more of me there are, the more darts I can make” he proclaimed while some of his copies already rushed to get to the tunnels.

“Wait!” I yelled but soon after they were all gone.

Frantically, I follow them to the lungs.

Once I arrived there, I was shocked to see the damage and the chaos. It seemed to have gotten much worse since I left.

“How long have I been gone?” I wondered. So many of my family members were here now, all followed the floating messages to come. Everybody was buzzing around, trying to help as best as they could.

Amidst this chaos I saw Tess and her clones. Like Nahla they were killing the obsessed guardians. But they were much faster than Nahla was. They were wielding their sharp swords, stabbing only the ones infected.

Somehow, they knew exactly who to kill.

Then there was Ben and his clones. The moment they finished making their darts they floated around everywhere.

Magically, they only stuck to the virus. The darts were catching hundreds if not thousands of viruses and forming large clusters.

I was standing in a war zone. It was in full motion. Yet, it felt surreal and chaotic. Somehow though, when I watched it long enough, I realized that there was an order to the chaos and that there was hope.

It felt like an eternity before the invasion was declared to be over.

Everybody here was exhausted. Weakened by what turned out to be days of fighting, we all stared blankly at each other and at the damage done.

Nahla, Tess and her copies had killed many, many guardians.

Where the guardians once stood, there was a big wound. It was patched up with a temporary construction.

Fortunately, some of the guardians who were furthest away from the viral attack had survived. As soon as the virus was declared dead, the guardians who were still alive started multiplying and moved side-by-side, step-by-step towards the wound.

Soon they would have sealed the gaps and our walls would be intact again.

Illustration: MAX (scientific name: Macrophage; from macro- big and phage- to eat)

While we all watched the repairs of the wound my brother Max was in his element. He came here to help with the cleaning.

Meticulously he ate up all the bits and pieces of whatever was left of the dead guardians and of any structures that got destroyed during the fight. After days of repair work, the guardians were standing shoulder-to-shoulder again and most of my family had left. But Tess and Ben stayed. “We told our copies that they can leave, but we will stay here.” Ben told me, while turning his head to Tess. She nodded. “It’s better that way. If this virus will ever come back, we are prepared. We will kill it in an instance.”

And to demonstrate her point she took out her sword again.

Ben and I took a safe step back. That virus will never have a chance against these two.

Snippets of science:

Here you find more elaborate explanations about scientific facts that are woven into the story.

The family of immune cells:

Didi, a Dendritic cell, is part of a huge family. Dendrite means branching, tree-like. Her name implies that she has very long arms she can stretch out. She has multiple brothers and sisters. Her sister Nahla is a Natural Killer cell. Tess is a Cytotoxic T cell. T stands for thymus, the immune organ close to your heart where Tess is born and cyto- meaning cell and toxic- poisonous. Both Nahla and Tess can kill other cells. Tamara is also a T cell. She is Helper T cell. She helps Ben, a B cell (B as Bone Marrow- the place he is born) to make sophisticated darts (antibodies). Max’s scientific name is Macrophage; from macro- big and phage- to eat. He loves to eat, a lot, all of the time. The Guardians are not immune cells but are essential to the story. They are called epithelial cells and form the wall between the inside of your body and the outside.

How can all these cells communicate? They send each other messages in the form of floating words that leave a trail that can be followed to its source. Scientifically these are proteins that are called cytokines, from cyto- cell and kines- movement- I guess a literal translation would be ‘to set us cells in motion’. And indeed, cells move around quite a bit. Here, they like to meet in their nearby houses, the lymph nodes. The lymph (lympha in Latin means water) is the clear fluid that runs through the lymph tunnels. Lymph tunnels and lymph nodes (where these tunnels intersect) also run through the whole body.

How antibodies are made

After Didi has caught the virus, she eats it, digests it and shows these pieces to the other cells she meets in the lymph nodes, or nearby houses. When the virus is broken up into tiny pieces, essentially molecules, they are referred to as antigens- substances that can induce an immune response. These pieces (antigens) can trigger Tess (a cytotoxic T cell) to act and kill cells that are infected with this particular virus. If Tamara (a Helper T cell) helps Ben (a B cell), they can make sophisticated darts (antibodies). Ben can make different types of antibodies, sometimes also called Immunoglobulins. The first rudimentary type (version 1.0, so to speak) is of the type M (Ben doesn’t need help from Tamara to make this one). Then there is type A, which is ideal for places like the lung or the gut- anywhere where there is mucus or slime. And finally, the most sophisticated missile is of type G for which Ben definitely needs Tamara’s help. For completion, there’s also type D and E (which we leave for another time).

How to fight an invisible virus

Natural killer cells like Nahla investigate cells on a regular basis for odd appearance or behavior. Normally cells show parts or molecules of what’s inside on their outside, so cells like Nahla can judge how healthy they are. However, in this case, the virus-infected guardians (the epithelial cells) seem to be hiding something. Lots of viruses deliberately stop this showcase, in an attempt to hide from the immune cells. Fortunately, natural killer cells know better. In particular, this very suspicious behavior activates them and tells them that they need to kill the infected cell.

A virus generally travels light. It is only made up of DNA or RNA which is often packaged into a capsule. Because it travels so light, it doesn’t have enough equipment to replicate itself so it can spread from one cell to another- or from one person to another. So, it hijacks the guardian’s own body (in this story it infects the guardians, but other viruses can infect other cells) and forces it to build more viruses. Now, they are obsessed and the only thing they care about is making more viruses. One way to stop this, or at least to delay the spread of viruses is for the infected cells to ‘go into stand-by mode’. So-called interferons signal the cells that they should do this. While these actions delay the virus’s spreading, Didi still needs to get specialized help. She can recognize a virus by its suspicious, free-floating DNA or RNA or it’s capsule, but she’s still not sure exactly what she is dealing with. Therefore, she finally finds Tess to help her. As a cytotoxic T cell, she has the ability to selectively kill infected cells. Ben can also assist the fight when he makes darts (antibodies) which can attach to the virus and thus prevent it from entering into the cell it wants to infect. As a result of all this fighting, lots of cells get damaged. In the lung this can cause difficulty breathing, as the chambers (alveoli) fill with fluid and prevent the exchange of gases (oxygen and carbon dioxide).

Attracted by the inflammation, the collective activation of immune cells, hundreds if not thousands of immune cells are recruited to the site where the virus invades. They all do their best to help with this fight. This cost a lot of energy. Maybe you remember, when you’re sick you are often weak and exhausted. This is due, in part, to the huge energy consumption of your immune cells and consequently to the repair of damaged tissue and cells once the virus is defeated.

Innate and adaptive immune cells

Researchers studying the immune system make a distinction between cells which work at the fore-front (they are called innate) and the specialists (they are called adaptive). Innate immune cells respond very quickly (like Nahla) but are not really specific to a certain invader. Whereas adaptive immune cells can make tailor-made weapons (like Tess and Ben). These weapons are very efficient but take about a week to be made. This is why both, innate and adaptive cells are crucial. Only when they succeed to work hand-in-hand together the invader can be killed. Once the fight is won, Tess and Ben will remember what the invader looked like. They are trained now and will fight the same invader even faster if it comes back. This is your immunological memory. How long they will remember depends on a lot of factors and can range from weeks to years, or even last a lifetime.

Text by Frederike Schmitz, Illustrations by Evelien Jagtman

©2020 by analytic translations