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

by Philipp Dettmer

Sure, they are not optimized like the other Antibody classes, but they are available extremely quickly,

your cells need oxygen and nutrients to keep themselves going and discard dangerous waste that is a byproduct of the cellular metabolism.

the Swamp Kingdom of the Mucosa. The swamp kingdom needs to solve the immense problem of being easy to cross for nutrients and substances the body wants to get rid of, while being hard to cross for pathogens at the same time. This means that in and around the swamp kingdom the immune system has to be different than in the rest of the body.

the immune system of the swamp kingdom can’t be as aggressive as the immune system in other parts of the body or it would simply destroy the places made for the exchange of gases and resources,

In the mucosa the Immune System had to learn to tread more lightly and to act as locally as possible when provoked. Yet at the same time, the mucosa is the most vulnerable area of the whole body,

The first line of defense employed by the swamp kingdom is the swamp itself. The mucus layer

It covers all of your surfaces that interact with the outside that are wrapped inside you. Mucus is continuously produced by Goblet Cells

And mucus is not just a sticky barrier but also filled with unpleasant surprises similar to the desert kingdom: salts, weaponized enzymes that can dissolve the outsides of microbes, and special substances that sort of sponge up crucial nutrients that bacteria need to survive, so they starve to death inside the mucus. In most places your mucus is also saturated with deadly IgA Antibodies.

it also protects your body from itself.

also moves.

A vast network of fine cilia, tiny organelles that look a bit like hair, cover the membranes of the special cells that make up the first layer of the mucous membrane: Epithelial Cells

they play a crucial role in your defense as they are especially great at activating your immune system and at calling for help with special cytokines.

But the Swamp Kingdom of your Mucosa is not really a single kingdom—it is much more like an alliance of different kingdoms that are all very different from each other but working together with a common goal.

Again imagine your guts as a long tube reaching through you, trapping a bit of outside inside you. On this outside, on your gut mucosa, around thirty to forty trillion individual bacteria from around 1,000 different species and tens of thousands of species of viruses make up your gut microbiota

we’ll explore a little how it is possible that this coexistence with so many guests is even possible.

There is a never-ending stream of attacks and your gut immune system has to perpetually react and separate friends from foes, more than in any other place of your body.

Millions of years ago your ancestors made a fragile deal with a team of microbial species—humans provide them with a long, warm tunnel to live in and a constant stream of stuff they can eat, and in turn they break down carbohydrates that we can’t digest and produce certain vitamins that we can’t make ourselves. The bacteria of the microbiome are tenants of sorts and these resources are the rent they have to pay.

These bacteria are called commensal bacteria

So to keep everything nice and peaceful, the bacteria of your gut live on top of the mucus layer of your gut, just like bacteria on your skin live on top of your skin.

every second of your life, a bunch of commensal bacteria wander deeper into your body. And this is a problem,

So the mucosa of your intestines is built in a way to prevent that.

First a layer of mucus filled with antibodies, defensins

and other proteins that kill or damage bacteria.

if the first protective layer were too good, you would starve to death.

Below the mucus layer, the intestinal epithelial cells are the actual barrier between the inside and the outside. Similarly to your lungs, the layer of epithelial cells protecting your insides is only ONE cell thick.

So below the epithelial wall is the third layer of the gut mucosa, the Lamina Propria, which is the home of most of the immune system of your gut. In the Lamina Propria, directly below the surface, special Macrophages, B Cells, and Dendritic Cells are waiting to greet the unwelcome guests:

Your intestinal immune system really does not want to cause inflammation if not absolutely necessary, because inflammation means a lot of extra fluid in the intestines, which you experience as diarrhea.

diarrhea is still a huge killer, responsible for about half a million dead children each year.

the Macrophages guarding your intestines

do not release the cytokines that call in Neutrophils and cause inflammation.

The Dendritic Cells of your gut behave in a special way too. Many of them sit directly below the layer of epithelial cells and squeeze their long arms between them, reaching right into the mucus of the gut. This way they can constantly sample the bacteria that are cheeky enough to not stay in their lane but venture too deep.

Around your gut, special types of B Cells produce nothing but large amounts of IgA Antibodies, the Antibody that works especially well in mucus.

And IgA does not activate the complement system and does not trigger inflammation,

All in all, around 30% of your poop consists of bacteria—and a lot of them have been clumped up by IgA Antibodies

All of these mechanisms are a horrible idea though if there are real invaders,

your gut has a type of special lymph node called Peyer’s patches that are directly integrated into your intestines. Microfold Cells (the same cells that we briefly met in your tonsils) reach directly into the intestines and take samples of things they think might be interesting for the immune system to take a look at.

So let’s explore your (arguably) most sinister enemy, the virus.

So it is known that your gut microbiome and how healthy it is has a strong association with how healthy you are and what you can handle.

One of the things making it possible for Clostridium difficile to become a problem in the first place is a weakened natural gut microbiome. Poop transplants have been shown to have a high chance of restoring the natural balance and help the patients to get rid of the invaders on their own.

A virus is not much more than a hull filled with a few lines of genetic code and a few proteins. They completely rely on proper living things to stick around.

Whatever the truth is, viruses turned out to be incredibly successful. In fact, viruses are arguably the most successful entity on the planet. It is estimated that there are 1031 viruses on earth. Ten thousand billion, billion, billion individual viruses.

They don’t have a metabolism, they don’t react to stimuli, and they can’t multiply. Viruses are so basic that they have no way to actively do anything. They are literally particles floating around in the environment and have to rely on passively stumbling into victims by pure random chance.

they abuse a weak point of all cells that living things will never be able to completely protect against: They attack receptors.

viruses can’t attach to just any cell—only to the ones that have a receptor they can attach to.

there are a lot of viruses—but only about 200 different species infect us humans.

a virus transfers its genetic material into its victim and forces the cell to stop making cell stuff. It is turned into a virus production machine.

Pathogenic viruses are excellent at circumventing the immune system because they have a superpower: Nothing multiplies as fast as they do. And that also means that nothing mutates or changes as fast as viruses.

they mutate all the time

the chances that among a few thousand mutations, one is extremely beneficial and able to make a virus significantly better suited to survive is pretty high.

it doesn’t have a metabolism that releases garbage chemicals that can be picked up by immune cells.