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

by Philipp Dettmer

So if a Neutrophil encounters a bunch of bacteria in one place it will just shower them with granules that rip their outsides apart.

But the most mind-boggling thing Neutrophils do in battle is to create deadly nets of DNA, sacrificing themselves in the process.

they create a Neutrophil Extracellular Trap. Or NET for short.

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.

you produce around one billion Neutrophils per two pounds (a kilogram) of body weight;

Another neat little detail about Neutrophils is that when they are chasing a pathogen, they often do so in swarms that follow the same mathematical rules as swarms of insects.

Inflammation is the universal response of your immune system to any sort of breach or damage or insult.

its purpose is to restrict an infection to an area and stop it from spreading, but also to help remove damaged and dead tissue and to serve as a sort of expressway for your immune cells and attack proteins directly to the site of infection!

chronic inflammation is involved in more than half of all deaths each year as it is an underlying cause of a wide variety of diseases—from various cancers to strokes or liver failure.

inflammation is a process that makes the cells in blood vessels change their shape, so that plasma, the liquid part from your blood, can flood into a wounded or infected tissue.

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.

Certain parts of the guts of your cells, like DNA or RNA, are high-alert triggers for your immune system and cause rapid inflammation.

Mast Cells are large, bloated cells filled with tiny bombs containing extremely potent chemicals that cause rapid and massive local inflammation.

Macrophages and Neutrophils order inflammation when they are engaged in a battle.

mitochondria, the powerhouse of the cell, were ancient bacteria that merged with the ancestors of your cells to become a symbiotic organism. Today they are organelles inside your cells that provide the cell with useful energy. Your immune system still remembers them as bacteria though, as intruders that have no business being outside cells. So if your cells burst and your immune system detects mitochondria floating around, your immune cells will react super alarmed.

At this point we have totally been ignoring another pretty important detail: How do cells know which way is which and where to go and where they are needed?

Well, in a way, cells smell their way through life. For cells, information is a physical thing: Cytokines. In a nutshell, cytokines are very small proteins that are used to convey information. There are hundreds of different cytokines and they are important in almost every biological process going on inside of you—from

cytokines are the language of your immune cells.

Let’s say a Macrophage floats around and stumbles over an enemy. The discovery needs to be shared with other immune cell buddies, so it releases cytokines

Somewhere else, another immune cell, maybe a Neutrophil, smells these cytokines up and “receives” the information. The more cytokines it picks up, the stronger it reacts to them.

But this is not all, the smell of cytokines also functions as a navigation system.

it can precisely locate where the message is coming from and then begin moving in that direction.

cells have a 360° smell system. They can pretty precisely tell from which direction a cytokine is coming from.

This information is used to orient the cell in space and then make it move towards its target, always following the path where the most cytokines are coming from.

A signal needs to pass a specific threshold to compel a cell to do something.

Not only does the intensity of the smell call more cells to help, it also makes sure that an immune response shuts itself down.

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

Inflammation rises massively and is no longer limited just to the place of infection. Immune cells flood the affected organs and can cause profound damage.

How exactly do cytokines convey information and what does this mean?

The chemistry of life causes sequences of interactions between proteins that are called pathways. The activation of pathways causes behavior.

receptors on cell surfaces. They are the noses of your cells.

So to summarize the important parts: Cells have millions of noses on their outsides that are called receptors. They communicate by releasing proteins that carry information, called cytokines. When a cell smells cytokines with their receptors (noses), they trigger pathways inside the cell that change their gene expression and therefore the behavior of the cell. So cells can react to information without being conscious or having the ability to think, guided by the biochemistry of life. This enables them to do pretty smart things even though they are technically very stupid. Some cytokines do also function as a navigation system—an immune cell can smell where they are coming from and literally follow their noses to the battlefield.

Chemokines are a family of small cytokines secreted by cells.

their main ability is to motivate cells to move in a certain direction.

Cytokines are a diverse group of information proteins that make your immune cells do a lot of different things. One of them is to make them move.

One of the first things we learned was that your Innate Immune System distinguishes self from other. But how does the Innate Immune System know what and who to attack? Who is self and who is other

All life on earth is made from the same fundamental molecule types that are arranged in different ways: carbohydrates, lipids, proteins, and nucleic acids.

the shape of a protein determines what it can do and how it can interact with other proteins, what structures it can build, and what information it can convey.

For some specific jobs, the protein puzzle pieces of life can’t be altered and still keep their function. It doesn’t matter how much a bacterium mutates

So over hundreds of millions of years, the innate immune system of many animals evolved to sort of save the shapes of certain puzzle pieces that are used only by enemies like bacteria.

And it so happens that your innate immune cells have receptors that can recognize the protein puzzle shapes

Your innate immune system can recognize quite a variety of proteins with a few receptors.

Every bacteria has some proteins that it can’t get rid of. And your innate immune cells come equipped with a very special group of receptors that are able to recognize all the most common puzzle pieces of our enemies:

The immune system of all animals has some variant of Toll-Like Receptors,

Neither bacteria, viruses, protozoa, nor fungi can completely hide from these receptors no matter what they do.

This principle of cells identifying the puzzle pieces of enemies with sort of sensory receptors on their surfaces is called microbial pattern recognition

why does the body of a woman not recognize sperm cells as other and kill them right away? Well, it does! This is one of the reasons you need about 200 million sperm cells to fertilize a single egg!

The Complement System is the most important part of your immune system that you have never heard of. Which is pretty weird because so much of your immune system is made to interact with it and if it doesn’t work properly the consequences for your health are immense and quite dire.

Basically the complement system is an army of over thirty different proteins (not cells!) that work together in an elegant dance to stop strangers from having a good time inside your body. All in all, about FIFTEEN QUINTILLION complement proteins are saturating every fluid of your body right now.

It maims enemies and makes their lives miserable and unfun. It activates immune cells and guides them to invaders so they can kill them. It rips holes into things until they die.