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

by Philipp Dettmer

Let us meet the third (and luckily last) cell that thinks allergic reactions are such a great idea!

Eosinophil makes sure that the symptoms of an allergic reaction stay around for a while—only a few of them exist inside your body and they tend to hang out in the bone marrow, far away from the action. Cytokines released by Mast Cells and Basophils activate them but they take their sweet time, proliferating and cloning themselves for a while before they arrive late to the party, where they unfortunately repeat the mistakes made before and cause inflammation and misery. You may rightfully ask now: Why do your own immune cells do this?

IgE Antibodies were originally supposed to do:

They are the immune system’s superweapons against large parasites that are too big for your phagocytes, your Macrophages, and your Neutrophils to swallow.

one of the most horrible parasites: Pa...

There are nearly 300 species of parasitic worms who can infest humans. And while only around a dozen of these species are widespread,

Most species of these parasitic worms tend to establish stable chronic infections that can persist for up to twenty years,

Take hookworms, for example, parasites that are about half an inch long and live in your guts. Their name is their game, as they hook themselves into the walls of your intestines and can cause extensive blood loss.

The hookworms produce eggs that leave through your feces and when the eggs turn into larvae, they bore through the skin of a new host and migrate to the lungs from where they ultimately end up in the small intestines again, to repeat the

Stage one is to recognize the worm and prepare a brutal attack.

if you consider Mast Cells weapons, IgE Antibodies activate them and remove the safety pins. If the immune system then encounters the worm again, Mast Cells can connect to them with the IgE Antibodies on their surfaces and vomit their harsh weapons directly onto them from very close range.

in later and continue to attack the worm and its eventual buddies in the coming hours and days. With this combined effort from these

Or put simply: Worms release a plethora of chemicals to downregulate and modulate your immune system to make it weaker.

unintended. For one, a weaker immune system is worse at preventing infection from viruses and bacteria and it might have a harder time catching cancerous cells before they become a deadly threat.

Worms suppress the mechanisms that cause inflammation reactions, allergies, and autoimmune diseases. We will learn a bit more about autoimmune diseases in the next chapter—but in a nutshell, if the immune system is downregulated to be less aggressive, it also can’t do as much damage to the body. Because

In evolutionary terms, humans in developed countries in the last few hundred years or so suddenly lost their parasitic wormy guests. The advent of soap and hygiene and the clear

separation of poop and drinking water destroyed the life cycles of most of the worms that were living within us.

So the idea makes sense that without wormy stimulation, these weapons just found new targets.

Autoimmune diseases. They are what happens when the immune system thinks your body is other—and that it needs to be destroyed.

Your body takes autoimmunity very seriously, as we learned by looking at the Murder University of the Thymus,

Security mechanisms can fail in such an unlucky sequence of events that your immune system thinks the body it was made to protect is the enemy that it needs to kill.

Autoimmune diseases don’t just happen though. For most people they are a colossal case of bad luck.

What needs to go wrong for your immune system to get so horribly confused? Well, there are a few stages, a few conditions that need to be met:

First of all, your MHC molecules actually need to be physically able to bind to your own self-antigen efficiently. This is mostly genetic, and as everything that is etched into our genetic code, bad luck.

The second thing that needs to happen for an autoimmune disease to develop, is that you need to produce either a T or a B Cell that is actually able to recognize self-antigen and that does not get killed by your own body.

And here it becomes very tricky. We spent a good portion of this book talking about the fact that your Adaptive Immune System does not just activate by itself. It needs the Innate Immune System to make the decision to activate it, and for that you first need a battleground. An environment that can push your Innate Immune Cells to escalate an immune reaction. How exactly these things happen is hard to say and even harder to observe in living humans—people get sick all the time but only extremely rarely does this lead to anything more than an infection that is cleared out eventually. But for most autoimmune diseases, these seem to be the steps that cause them:

Step one: There are individuals who have a genetic predisposition.

Step two: They make B or T Cells that are able to recognize a self-antigen.

Step three: An infection provokes the Innate Immune System into activating these faulty B or T Cells.

But some pathogens will also try to mimic the shapes of their host, which makes a lot of sense, since this

For a pathogenic virus or a bacteria your tissue is a jungle full of angry predators that are looking for them, so mimicking the environment to become harder to spot is an effective strategy.

Even after the actual infection has been wiped out, these cells will find the autoantigen (or self-antigen) presented by civilian cells and just assume there are still a lot of enemies around.

Meanwhile, the activated Helper T Cell starts activating B Cells that can accidentally fine-tune themselves on the self-antigen!

And when B Cells mature into Plasma Cells, Memory Cells are created as a byproduct. So now all of a sudden, in your bone marrow, Long-Lived Plasma Cells begin regularly pumping out autoantibodies against your own body. They will live for years and decades. Once your adaptive

No matter how many civilian cells your immune system kills, your body will make more—and so chronic inflammation, chronic immune system activation, is the consequence. Your misguided immune cells think they are perpetually surrounded by enemies and act

So at least for now, there is no cure available for autoimmunity—once you have it, you need to deal with it. To alleviate pain and inflammation, generally autoimmune diseases are treated with a variety of medication that suppresses the immune system, particularly inflammation, which as you may imagine, is not great either. It may alleviate the symptoms of autoimmunity by making the immune system weaker and less likely to attack the body but it also leaves the patient more vulnerable to infections.

about anergy, which is a passive and pretty ingenious tactic your immune

system deploys to deactivate T Cells that are autoreactive, meaning able to recognize your own cells.

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.

The rates of diseases like multiple sclerosis, hay fever, Crohn’s disease, type 1 diabetes, and asthma have increased by as much as 300% in the last century. But this is not all: It seems like you can draw a direct line from how developed and rich a society is to how much of its population suffers from some kind of allergy or autoimmune disorder.

The perceived message was clear: In our fervor to rid ourselves from the causes of disease, humans had become too clean and sterile and had committed a sin against nature, and now we were suffering immune disorders because of it!

The solution seemed to be equally easy and straightforward! Just be less clean, stop washing your hands, maybe eat a little spoiled food, pick your nose. In short: expose yourself and your children to microorganisms and maybe even contract

the reality seems to be way more complicated and nuanced.

For example, a widely held view is that it is good for us to contract diseases because surviving them makes us stronger, since this has been the natural way humans operated in the past.*

the worst bacterial and viral pathogens that cause infectious diseases and make our lives miserable in modern times are new to our species in evolutionary terms.

Living close together created a perfect breeding ground for infectious diseases. Suddenly, in evolutionary terms, there were hundreds or even thousands of victims to infect. As our ancestors were not aware of the nature of microorganisms or even basic hygiene and they did not yet possess tools like soap and indoor plumbing, there was not much they

could do—on the contrary, their lack of understanding made things worse.

As a consequence, virtually every infectious disease we know today arose in the last ten thousand years. From cholera, smallpox, measles, influenza, and the common cold to chicken pox.

Hygiene is incredibly important to protect us from all of these diseases.

Hygiene is often confused with cleanliness—but you really should understand it as a targeted approach to remove potentially dangerous microorganisms from the key places and situations where they can make you sick.