Immune: A Journey Into the Mysterious System That Keeps You Alive

by Philipp Dettmer

Your real weak points to infections are your mucous membranes—the surface that lines your windpipe and lungs, eyelids, mouth, and nose, your stomach and intestines, your reproductive tracts and bladder. It is hard to give their total surface area since numbers vary so much from person to person, but on average there are about 200 square yards (meters) of mucous membranes in a healthy adult (about the same as a tennis court), most of them being your lungs and your digestive tract.

Proteins are made from chains of amino acids, which are tiny organic building blocks that come in twenty different varieties. All you need to do is to string them together into a chain, in whatever order you like, and voila, you have a protein. This principle enables life to construct a stunning variety of different things. For example, if you wanted to make a simple protein from a chain of ten amino acids, and you have twenty different amino acid types that you can choose from, this gives you a breathtaking 10,240,000,000,000 different possible proteins.

In a nutshell, the instructions on the DNA are converted into proteins in a two-step process: Special proteins read the information on the DNA string and convert it into a special messenger molecule called mRNA—basically the language that our DNA uses to communicate orders. The mRNA molecule is then transported from the nucleus of the cell to another organelle, the protein production machinery called the ribosome. Here the mRNA molecule is read and translated into amino acids, that are then put together in the order inscribed into it. And voila, the cell has made a protein from your DNA. So your DNA is basically a bunch of code, with sections called genes, that are a protein-building and regulation manual for your cellular machinery.

to us. Trillions of them act as friendly

This is what Neutrophils do when they create a Neutrophil Extracellular Trap. Or NET for short. If Neutrophils get the impression that drastic measures are called for, they begin this crazy kind of suicide. First their nucleus begins to dissolve, freeing up their DNA. As it fills up the cell, countless proteins and enzymes attach to it—the sharp bone splinters from our little story. And then the Neutrophil literally spits out its entire DNA around itself, like a giant net. Not only can this net trap enemies in place and hurt them—it also creates a physical barrier that makes it harder for bacteria or viruses to escape and move deeper into the body. Usually the brave Neutrophil dies doing this, which seems obvious.

The injured toe becomes hot as the blood brings extra body heat. This heat does useful things for you: Most microorganisms do not like it hot—so making the wound hotter slows them down and makes their lives stressful. And you want pathogens in your body to be as stressed as possible. In contrast, your civilian repair cells like the extra temperature very much as it speeds up their metabolism and enables your wound to heal faster.

The first way inflammation gets started is through dying cells. Amazingly, your body evolved a way to recognize if a cell died a natural way or if it died a violent death. The immune system has to assume that cells dying an unnatural death means grave danger, and so death is a signal that causes inflammation.

In some cases this whole system can break down though and have horrible consequences. If there are too many cytokines the immune system can lose all constraint, become super enraged, and overreact massively—which leads to an appropriately named cytokine storm.

this does not mean the others are not important but the principle is mostly the same and it is helpful to zero in on something.

This principle of cells identifying the puzzle pieces of enemies with sort of sensory receptors on their surfaces is called microbial pattern recognition and it will become even more important later on for the adaptive immune system, which uses the same basic mechanism, but in a much more ingenious way.

maimed

On top of serving as an emergency reservoir and a barracks, the spleen really is just a huge lymph node that filters your blood (and not your lymph fluid, like your regular lymph nodes do) and does all the things lymph nodes do. So when we discuss the function of lymph nodes in more detail, just remember that your spleen does the same thing, only with your blood!

People regularly lose their spleens, for example after traffic accidents where a strong blow to the torso can rupture the small organ critically, so that it has to be removed. Surprisingly this is not as deadly as you might think. Other organs like the liver, regular lymph nodes, and your bone marrow can take over most of its jobs. And about 30% of people happen to have a second spleen that is tiny but will grow and take over the job if the first one is removed.

Your tonsils are something like a center of your immune system intelligentsia in your mouth. A lot of different immune cells that we will get to know in this book work here to keep you healthy. To get samples to them, your tonsils have deep valleys where tiny pieces of food can get stuck. Microfold Cells, very curious cells that grab all sorts of stuff from your mouth and pull it deep into the tissue, where they show it to the rest of the immune cell to check out.

Microorganisms have a huge advantage over us meat giants. Consider how much effort it takes you to make even a single copy of yourself and your trillions of cells. To multiply you first need to find another flesh giant that thinks you are cute. Then you need to go through a complicated dance that hopefully leads to the merger of two cells from you two. And then you need to wait for months and months while the merged cell multiplies over and over and over, until it has become a few trillion cells and is released into the world as a hopefully healthy human. And even then you only have produced a single mini human that is actually pretty weak and needs years of attention and care before it stops being totally useless. It takes even more years before the offspring can repeat the dance and multiply again. Any sort of evolutionary adaptation to a new problem is super slow with our very inefficient ways.

How can your slow continent of flesh adapt to create specific defenses for each of the millions of different microorganisms and the millions more that don’t even exist yet? The answer is as simple as it is baffling: The immune system does not so much adapt to new invaders as it already was adapted when you were born. It comes preinstalled with hundreds of millions of different immune cells—a few for every possible threat that you could possibly encounter in this universe. Right now you have at least one cell inside you that is a specific weapon against the Black Death, any variant of the flu, the coronavirus, and the first pathogenic bacteria that will emerge in a city on Mars in one hundred years. You are ready for every possible microorganism in this universe.

In your body right now, there is at least one immune cell that has a receptor that can recognize one of the many millions of different antigens that can exist in the universe. Let us repeat that: For every possible antigen that is possible in the universe, you have the potential to recognize it inside you right now.

In principle, this is what your adaptive immune cells do with gene fragments. It takes gene segments and randomly combines them, then it does the same again, and then it randomly pulls out or adds in parts, to create billions of different receptors. They have three different groups of gene fragments. They randomly choose one from each group and put them together. This is the main course. Then they do this again, but with fewer fragments for the dessert. And then when they are done, they randomly remove or add in parts. This way your adaptive immune cells create at least hundreds of millions of unique receptors.

Each of them fitting one possible guest at the dinner party, which in this case is an antigen from a microorganism that could invade your body. So through controlled recombination, your immune system is prepared for every possible antigen an enemy could make. But there is a catch—this ingenious way to create such stunning variety makes your adaptive immune cells critically dangerous to you. Because what is stopping them from developing receptors that are able to recognize self, the parts of your own body? Well, their education is.

Helper T Cells are able to recognize an antigen only if it is presented in an MHC class II molecule. Or in other words, they eat a wiener only in a hot dog bun. Think of Helper T Cells as really picky eaters—they would NEVER even think to touch and eat a wiener that floats around by itself. No sir, that would be disgusting! Helper T Cells only ever consider eating a wiener if it is nicely presented to them in a hot dog bun. This makes sure that Helper T Cells can’t just get activated by accident because they pick up antigens that float around freely in the blood or lymph. They need to be presented with an antigen that sits in an MHC class II molecule, from an antigen-presenting cell. Only this way does the Helper T Cell have confirmation that there is actual danger and that it should get active!

Let us summarize one last time because this stuff is really important and really hard: To activate your Adaptive Immune System, a Dendritic Cell needs to kill enemies and rip them into pieces called antigens, which you can imagine as wieners. These antigens are put into special molecules, called MHC class II molecules, that you can imagine like hot dog buns. On the other end, Helper T Cells rearrange gene segments to create a single specific receptor that is able to connect to one specific antigen (a specific wiener). The Dendritic Cell is looking for just the right Helper T Cell that can bind its specific receptor to the antigen. And if a matching T Cell is found the two cells interlock. But then there needs to be a second signal, like a gentle encouraging kiss on the cheek, that tells the T Cell that all is good and the signal from the presented antigen is real. And only then does a Helper T Cell activate.

Step 1: A battle needs to occur and dead enemies, which are big chunks of antigens (turkey drumsticks), need to float through the lymph node. Here, a B Cell, with a specific receptor needs to connect to the antigen. If the dead enemy is covered in complement, activation will be much easier. This will activate the B Cell, which makes a lot of copies of itself and produces low-grade antibodies, but the B Cells will die after around a day if nothing more happens. Step 2: In the meantime, a Dendritic Cell needs to pick up enemies at the battlefield and turn them into antigens (wieners) which are put in the MHC class II molecules (hot dog buns) and travel to the T Cell dating area in the lymph node. Here it needs to find a Helper T Cell that is able to recognize the antigen with its unique T Cell receptor (eat the wiener from the bun). If this happens the Helper T Cell is activated and makes a lot of copies of itself. Step 3: The B Cell breaks the big chunk of antigen (turkey drumstick) down into dozens or hundreds of small antigens (wiener sized) and begins presenting them in MHC class II molecules (hot dog buns). Step 4: An activated B Cell that is presenting hundreds of different antigens (wiener-sized sausage pieces) needs to meet a T Cell that can recognize one of these antigens with its specific T Cell receptor, which is the second signal for the B Cell. Only if this exact sequence of events occurs does a B Cell get activated for real. Are you impressed yet with your biol...

Your B Cell that was properly activated through the two-factor authentication now changes. It has waited its whole life for this moment. It begins to swell, to almost double its size, and transforms into its final form: the Plasma Cell.*3 The Plasma Cell now begins producing antibodies for real. It can release up to 2,000 antibodies per second that saturate the lymph and blood and the fluids between your tissue. Like the Soviet rocket batteries in World War II that could send a never-ending barrage of missiles on enemy positions, antibodies are made in the millions and become every enemy’s worst nightmare, from bacteria to viruses or parasites. Even cancer cells. Or, if you are unlucky and have an autoimmune disease, your own cells.

In the oceans alone, every single second, one hundred thousand billion, billion cells get infected by viruses. So many, actually, that up to 40% of all bacteria in the oceans are killed by virus infections every single day. And even more, even your most intimate self is not safe from viruses: About 8% of your DNA is made of remnants of viral DNA. We’ll stop with the large numbers now because nobody can picture this stuff anyway. Let us just agree that there are a whole lot of viruses on earth and they seem to be doing quite all right.

OK, let us talk about one of the weirdest Nobel Prizes for medicine and how upsetting the past was and how great the present is. Syphilis is a sexually transmitted disease caused by spirochetes bacteria. Its possible symptoms are horrible and creepy and if you want to have a bad time you should go look up some pictures online. One of the possible late stages of the disease is neurosyphilis, an infection of the central nervous system. Patients affected by it basically would usually suffer from meningitis and progressive brain damage. What made the experience even more unpleasant were mental problems, from dementia to schizophrenia, depression, mania, or delirium, all caused by the bacteria wreaking havoc. Ultimately it is fair to say that affected patients had a bad time and in the end they would die without doctors being able to help them, other than to try to alleviate their suffering. But they did observe that in some cases patients that suffered from unrelated, very high fevers would actually end up being healed. So naturally, a few doctors began experimenting with pyrotherapy, a version of treatment by causing fever, and began injecting syphilis patients with malaria. This sounds horrible at first but it was a pretty acceptable risk—the patients would die anyway and malaria could already be treated at the time. Malaria was a prime candidate because it caused high fevers over a long and sustained time and basically cooked out the syphilis bacteria that just could not st...

First of all, just like the MHC class II molecule, the job of an MHC class I molecule is to present antigen. The extremely important difference between both molecules is: Only antigen-presenting cells have MHC class II molecules. This includes Dendritic Cells, Macrophages, and B Cells—all of them immune cells!

This is it—no other cell is allowed to have an MHC class II molecule.*2 In contrast to that: Every cell of your body that has a nucleus (so not red blood cells) has MHC class I molecules. OK, why is that and how does this work? As we said before, cells are constantly breaking down their proteins so their parts can be recycled and reused. The crucial thing here is that while this recycling happens, your cells pick a random selection of protein pieces and transport them to their membranes to display them on their surfaces. The MHC class I molecule showcases these proteins to the outside world, just like a fancy display window would showcase a selection of the items the inside of a store has to offer. This way, the protein story of what is going on inside the cell can be told to the outside. To make sure the story is always up-to-date, your cells have many thousands of display windows—or many thousands of MHC class I molecules—and each one gets refreshed with a new protein, about once a day.

An organ that is transplanted had to be taken out of another living being—to do that it had to be separated from it. Usually with sharp tools. This whole process is likely to have caused small wounds—what do wounds inside the body trigger? Inflammation, which then attracts the Innate Immune System. And if things go wrong, the Adaptive Immune System gets called right to the edges of the new life-saving organ and can call in more cells that check out the display windows only to find that they are not yours. This is the unfortunate reason that after you receive a donated organ, you need to be on strong medication that suppresses your immune system for the rest of your life. To minimize the chance that your immune cells find the foreign MHC class I molecules and kill the cells carrying them. But of course this will leave you much, much more vulnerable to infections.

Another way the Dendritic Cell can activate a Killer T Cell is by straight up being infected by the virus itself. Just like a regular cell, the Dendritic Cell presents samples of the virus in its MHC class I molecules and can still tell the adaptive immune system: “Look, there is a pathogen that infects cells, even I am infected, mobilize special forces especially for that type of enemy.” To enhance the chance that this happens, Dendritic Cells that sense the chemical warfare triggered by virus infections massively produce more display windows, to become super, extra transparent.

Natural Killer Cells do not look inside cells. Even if they wanted to, they couldn’t—they have no way to look into the display windows, the MHC class I molecules, and read the story of the inside of the cell. No, instead they do something different: They check if a cell has MHC class I molecules. Nothing more, nothing less. This is solely to protect against one of the best anti–immune system tactics virus and cancer cells have. Generally cells that are either infected or unhealthy do not show MHC class I receptors in order to hide what is going on inside them. Many viruses force infected cells to stop showing them as part of their invasion strategy, and many cancer cells just stop putting up display windows, thus making them invisible to the antiviral immune response that we have shown thus far.

When Natural Killer Cells check out a civilian cell for infection or cancer, if they have plenty of MHC class I molecules, as most healthy cells do, the inhibitor receptor is stimulated and tells the Natural Killer Cell to chill. If the cell does not have enough MHC molecules though, there are no calming signals and the Natural Killer Cell, well, kills. Killing in this case means that it orders the infected cell to kill itself through apoptosis, the regular and orderly cell death, which traps viruses inside the carcass. So Natural Killer Cells are a bit like nervous agents who are walking through a city, randomly approaching civilians. Instead of saying hi, they put a gun against your head and wait a few seconds. If you don’t show them your passport quickly enough, they pull a plastic bag over your head and shoot you in the face.

Let us use this moment to explain how antibiotics work. Like Prometheus who stole fire from the gods and gave it to humanity and made it more powerful, scientists stole antibiotics from nature to make it live longer. In the wild, antibiotics are typically natural compounds that microbes use to kill other microbes. Basically the swords and guns of the microworld. The first successful antibiotic, penicillin, is a weapon from the mold Penicillium rubens that works by blocking bacteria’s ability to make cell walls. As a bacterium tries to grow and divide it needs to produce more cell walls and Penicillium has a shape that interrupts this construction process and prevents the bacteria from making more of itself. The reason why you can safely be treated with penicillin is that your cells don’t have cell walls! Your cells are lined with membranes, which is a fundamentally different structure, so the drug doesn’t do anything to your cells.

Another antibiotic you may have heard of is Tetracycline, which was stolen from a bacteria called Streptomyces aureofaciens and works by inhibiting protein synthesis. If you cast your mind back to how proteins are made, you’ll recall something called a ribosome. Ribosomes are the structures that turn mRNA into proteins. So they are fundamental to the survival in both human and bacterial cells, because without new proteins, a cell must die. Human and bacterial ribosomes are different in shape and as a consequence of this difference, although they basically do the same thing, Tetracycline is able to inhibit bacterial ribosomes and not yours.*2

Activation usually begins with an initial exposure of immune cells to intruders, like bacteria, or danger signals, like the insides of dead cells. For example, Macrophages get activated when they notice an enemy and release cytokines that call up Neutrophils and cause inflammation. The Neutrophils themselves release more Cytokines, causing more inflammation and reactivating Macrophages, who continue fighting. Complement proteins stream into the site of infection from the blood, attack pathogens, opsonize them, and help the soldier cells to swallow the enemies. Dendritic Cells sample enemies and make their way to the Lymph Nodes to activate Helper T Cells or Killer T Cells, or both. Helper T Cells stimulate the innate immune soldiers to continue fighting and create more inflammation. Killer T Cells start killing infected civilian cells with support from Natural Killer Cells. Meanwhile, activated B Cells have turned into Plasma Cells and release millions of Antibodies that stream onto the battlefield and disable the pathogens, maiming them and making them much easier to clear up. This is the immune response in a nutshell.

If dead bacteria are mixed with substances that really put the immune system on edge, your immune cells will not be able to make the distinction but order the creation of memory cells. Unfortunately a number of people who don’t understand chemistry have deducted from this that vaccines are filled with poison, which could not be further from the truth. For one, the doses of these chemicals are laughably small and usually only able to create a local reaction. And without them, the vaccine would not work. Another upside for this kind of vaccine is that it is much more stable and easy to store and transport than live vaccines!

Now, after the exposure to the crabmeat, a lot of IgE Antibodies that are able to attach to the crabmeat allergen are in your system. But IgE Antibodies by themselves would not be problematic as they are not particularly long-lived and dissolve after a few days. They need help to become a problem from a special cell in your skin, lungs, and intestines that is especially receptive to IgE Antibodies: the Mast Cell.

Mast Cells have receptors that connect and attach to the butt regions of IgE Antibodies. So if IgE is produced after your first exposure to an allergen, Mast Cells swoop them up like a large magnet would swoop up a bunch of nails. So you can imagine a “charged and armed” Mast Cell as a big magnet, covered with thousands of tiny spikes. When allergens pass by, the IgE Antibodies on the Mast Cell can extremely easily connect to them. To make matters worse, IgE on Mast Cells is stable for weeks or even months—the connection protects them from decay. So, after your initial exposure to an allergen, you have these bombs in your skin, your lungs, or your gut, ready to get activated very quickly. Time passes and nothing happens, until you finally eat a bunch of crabmeat again and flood your system with the allergen enabling the Mast Cells covered in IgE to connect to it. Now the armed allergy bomb goes off inside your body. Your armed Mast Cells undergo degranulation, which is a nice way of saying that they vomit out all of their chemicals that are inflammatory superchargers, especially histamine. This causes virtually all of the very unpleasant things that you experience during an allergic reaction: It tells the blood vessels to contract and let fluid stream into the tissue, causing redness, heat and swelling, itching, and a general feeling of unwellness.

Even if there is no danger, a few of your Dendritic Cells, for example in your skin, will take samples of the stuff floating around in the natural, healthy environment between your cells—a lot of it is self-antigen presumably—and then move to your lymph nodes to show the Adaptive Immune System what it found. You may ask now: How on earth is this a good idea? Wouldn’t a Dendritic Cell that collects self-antigen cause autoimmune diseases? Well, think again—what is one of the main jobs of the Innate Immune System? To provide context to the Adaptive Immune System. So a Dendritic Cell that moves into a lymph node with the context of “everything is fine—this is what I have to show you” can actually prevent autoimmune diseases. Because what it is really doing is “hunting” for T Cells that are autoreactive. That is, able to bind their MHC molecules to your self-antigen. If the Dendritic Cell finds one of these autoreactive T Cells by pure chance, it connects to it to stop it from further wrongdoing. Remember the “kiss” signal the Dendritic Cell gives to T Cells to activate them? The confirmation signal that tells the T Cell that the danger is real? Well, if there is no danger, the Dendritic Cell withholds this kiss signal. And a T Cell that receives an activating signal on their MHC molecules but no loving kiss on the cheek deactivates itself. It doesn’t die immediately, but it can’t get activated again. It is a lame duck from now on and just floats around for the rest of its life...

Hygiene is a great idea that really benefits the health of our species. This whole point is so important that it is worth repeating: The microorganisms that are causing infectious diseases are comparatively new to our biology. Our bodies and immune systems did not have hundreds of thousands of years to evolve alongside them. Surviving the measles does not make you tougher, it just makes your life bad for two weeks. And if your immune system is not in good shape it might also just kill you. Dangerous pathogens are, well, dangerous. Clean water has literally saved hundreds of millions of lives. Hygiene, from washing your hands regularly to making sure your food is properly stored, is incredibly important—as important as vaccines, if not more. Hygiene is also a critical line of defense that keeps us safe from contracting dangerous infections, for example in the case of global pandemics. Coughing into your elbows, washing your hands regularly and properly, and wearing masks buys us time for larger-scale interventions, like vaccines or medication. Hygiene reduces our need to prescribe antibiotics, which automatically combats antibiotic resistance. It protects the weaker members of society like small children and seniors, the immunocompromised, people going through chemotherapy or suffering from genetic defects.

What is generally troubling about these appeals to naturalism is the idea itself, that something natural is somehow better. Nature does not care about you or any individual at all. Your brain and body and immune system are built on the bones of billions of your would-be ancestors who were not fast enough to escape a lion, were killed by a mild infection, or were just a little worse at pulling the nutrients from their food. Nature gave us charming diseases like smallpox, cancer, rabies, and parasitic worms that feast on the eyes of your children. Nature is cruel and without any form of care for you. Our ancestors fought tooth and nail to build a different world for themselves, a world without all this suffering and pain and horror. And consequently we should celebrate and marvel at the enormous progress we’ve made as a species. While we obviously still have a long way to go and the modern world has a lot of downsides, the notion that “natural is better” is something only people who are not actually living in nature can say, and who have forgotten why our ancestors worked so hard to escape it.

Would you like more aggressive and stronger Macrophages or Neutrophils? Well, this would mean more and stronger inflammation, more fever, more feeling sick and tired even if you encounter only small and minor infections. How about superstrong Natural Killer Cells to kill more infected or cancer cells? OK, but they might be so motivated that they eat away at healthy cells that just happen to be around! Do you want to boost your Dendritic Cells so that they will start activating the Adaptive Immune System more? That would drain and exhaust the resources of your immune system even for small dangers, leaving you open and vulnerable when a seriously dangerous infection happens. Or maybe you could boost your T and B Cells, making them much easier to activate, but which would cause autoimmune diseases as some of these cells will certainly begin attacking your own tissue. Once your boosted antibodies and T Cells have begun killing your heart or liver cells they will not stop until they have finished their job. Maybe this is all not dangerous enough for you, and you would rather boost your Mast Cells and the B Cells that produce IgE Antibodies, the combination of cells that is responsible for allergies. Food that was only mildly irritating to your bowel will now cause violent diarrhea or allergic reactions that could kill you in minutes. Is all of this too boring? Why not think outside of the box and boost all the regulatory parts of your defense systems so they shut your immune sy...

An infamous example is TGN1412, a drug trial that went so horribly wrong that it reached beyond the sphere of immunology and got some headlines in newspapers. The trial was supposed to look for side effects in humans taking a drug that was supposed to stimulate T Cells in cancer patients and make them survive longer. The drug was an artificial antibody that was able to connect to and stimulate the CD28 molecule on T Cells—we already met CD28 before without naming it—one of the signals T Cells need to be activated. We described it as a gentle kiss the Dendritic Cell needs to give a T Cell to activate it. So the idea of TGN1412 is pretty straightforward: Give T Cells an artificial “kiss” to stimulate them to be more effective and easier to activate in cancer patients. Basically “boosting” their immune system to be more formidable in the face of this life-threatening disease. And yeah, well, boost it did. For safety reasons, the amount of TGN1412 administered was 500 times lower than the dose that had led to any reaction in macaques (which is a cute species of monkeys, if you are wondering) and so the researchers doing the drug trials did not expect any real reaction to occur in the human volunteers. But instead, minutes after TGN1412 was given to healthy young men, all hell broke loose. It turned out macaques, the animals used to test the drug in animal models, happen to have way fewer CD28 molecules on their T Cells than humans and so they reacted way less strongly to the d...

Although there is an exception: Autoantibodies, a kind of antibody that can cause certain autoimmune diseases, are greatly increased. In a nutshell, if you smoke, your immune system does way more of the stuff that is bad and damaging for the body and at the same time it is worse at actually fighting your enemies, calling reinforcements, and stopping invaders from spreading. As a bonus consequence smokers have a harder time healing wounds because of their suppressed immune system not being able to help with healing as much as it should. Even if you stop smoking today, your immune system will stay suppressed for a week to months—so the earlier you quit the better. But it would be dishonest to say that there are not a few positive effects of smoking because the world is not binary: Sometimes having a toned-down immune system can be a good thing. Inflammation is a double-edged sword, indispensable for your survival, but also very harmful to you. Smokers suffer less often from inflammatory diseases simply because inflammation is regulated down if your immune system is behaving like a slug that ate a few hash brownies for breakfast. So in the case of certain inflammatory autoimmune diseases, like ulcerative colitis for example, smoking seems to offer some form of protection.

* There is this myth that your attitude is crucial when it comes to surviving cancer. The general idea is that if you have and display a positive attitude, you will activate some mystical force in the immune system and enable it to overcome the disease. Inversely, a really negative attitude may have the opposite effect and make it harder for your body to beat the disease or may even have caused it. Wherever the idea of your attitude affecting your cancer survival chances originally comes from, after decades of research it has become clear that with an extremely high certainty, your attitude has no effect on your chances of surviving cancer. Your immune system does not magically become better or worse at fighting cancer if you are or are not positive and happy. Still, this myth is going strong, as it appeals to our culture of self-empowerment and agency and is spread by many well-meaning people. But aside from the fact that there is no solid science to prove a relationship, it is a terrible thing to say to someone with cancer that their attitude matters and that they should stay positive, because it does two things: For one, it puts the responsibility of healing and surviving on the sick person. It implies that if you don’t win the fight and have faced the gravest of all outcomes, it is your fault. That if you just had been more positive and optimistic, no matter how you really felt, that you could have saved yourself. Which is an incredibly unfair burden to put on someone ...

The coronavirus targets a specific and very important receptor called ACE2. This receptor has a few vital jobs in your body, specifically regulating your blood pressure, which means you have a lot of cells in your body that carry it and can be infected. If you guessed that the epithelial cells in your nose and lungs have plenty of this receptor, you’d be right. From the perspective of a coronavirus, your lungs are miles and miles of free real estate. But the ACE2 receptor also sits on cells in a variety of tissues and organs around your body. Your blood vessels and capillaries, your heart, your gut, and your kidneys. All of them have ACE2. As we learned before, your body’s first response to a viral infection is chemical warfare, which basically does three main things: Interferons interfere with virus reproduction and slow it down, while other cytokines cause inflammation and alert immune cells. Now, one thing that makes the coronavirus so dangerous is that it seems to be able to shut down (or strongly delay) the release of interferons, while the infected cells still release all the cytokines that cause inflammation and alert the immune system. So the virus is able to infect a lot of cells and spread quickly without being slowed down, while at the same time triggering widespread inflammation and activating immune cells that will themselves cause even more inflammation.*1