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

by Philipp Dettmer

color of your snot

just tells you how severe the inflammatory reaction inside your nose is, not what caused it. The more colorful, the more Neutrophils have given their life.

Within three days after the initial infection with influenza A, the replication of the virus infection peaks as the innate immune system is catching and killing as many viruses as possible.

Since viruses spend most of their time inside infected cells, it is simply too hard to catch all of them when they float from cell to cell. If your immune system could fight viruses only when they were outside cells, they would be nearly unbeatable and humans might not be around today.

The best way to kill a lot of viruses is to destroy infected cells, and the viruses inside them. Let us pause for a moment to appreciate the magnitude of what we are talking about here. Your immune system needs to be able to kill your own cells. Your immune system has an actual license to kill you.

they let you know they never get sick even though you didn’t ask them?

The best way to react to this kind of outburst is to nod politely and change the subject.

Remember in the chapter “Smelling the Building Blocks of Life,” we learned that cells can smell their environment and recognize intruders and their excretions with toll-like receptors that can recognize the shapes of different enemy molecules.

still a very significant blind spot, the insides of infected or corrupted cells.

Cells that are infected or corrupted need to be identified so they can be killed before they can cause large-scale damage,

So, to detect the danger of these corrupted cells, your immune system has developed an ingenious way that makes it possible for your cells to look inside other cells.

They are filled up with millions of different proteins, with many different jobs and functions, that work together in a beautiful concert of life.

these proteins are more than just materials and parts. They tell a story. A story of what is going on inside a cell.

what notes the conductor wants the orchestra to play. And of course, if there is something wrong.

But your immune cells can’t look through the solid membrane of your cell to check what kinds of proteins

by using a very special molecule that works like a display window.

MHC class I molecules are display windows. MHC class II molecules are hot dog buns! Very different things, annoyingly similar names!

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 is it—no other cell is allowed to have an MHC class II molecule.*2

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.

This way, the protein story of what is going on inside the cell can be told to the outside.

Every cell in your body that has a nucleus and protein-production machines does this constantly. So your cells constantly showcase what is going on inside them, to assure the immune system that they are fine.

In the case of our influenza A infection the mechanism works like this: Remember that the first thing the viruses did when they successfully invaded your cells was to take over the production sites of the cell. They used the tools and resources of the cell to make virus protein parts, virus antigens.

If an immune cell wants to check if a cell is infected, it simply can move closer and peer into the little “windows” to get a snapshot of the inside. If it recognizes things in the windows that should not be inside the cell, the infected cell will be killed.

One of the most important things that happens during the chemical warfare triggered by interferon is that cells are

stimulated and ordered to make more MHC class I molecules. So in case of an infection, interferon tells all cells in the vicinity to build more windows and become more transparent, to tell more of their interna...

This is incredibly important and unfortunate for one thing though: Organ transplantation.

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.

Back to the MHC class I molecule, the window into the cell. Let us meet one of your most dangerous cells that entirely depends on the display window. A brutal killer from the Adaptive Immune System that is one of your strongest weapons against viruses. The Killer T Cell, the murder specialist of your body.

There is a whole library of proteins like these and their presence, in anything but embryos, tells the immune system that something is off. So these proteins are not technically faulty because they are serving your tumor well, but they are definitely abnormal and thus a sign of danger for your body.

The teacher cells in your Thymus because they need them to educate your Helper T Cells and make sure they can recognize MHC class II molecules properly!

Killer T Cells are the siblings of Helper T Cells but their job is very different. If the Helper T Cell is the careful planner that makes smart decisions and shines through its ability to organize, the Killer T Cell is a dude with a hammer that bashes heads in while laughing

Around 40% of the T Cells in your body are Killer T Cells and, just like their Helper T Cell siblings, Killer T Cells come with billions of possible different and unique receptors for all sorts of possible antigens. They too have to pass the education of the Murder University of the Thymus before they are allowed to enter general circulation.

All you need to know is that there is a thing that Dendritic Cells do called cross-presentation, which enables them to

sample virus antigens and to present some of them in their MHC class I molecules, in their display windows, even though they have not been infected by a virus. So Dendritic Cells are able to activate Helper T and Killer T Cells at the same time, by loading up hot dog buns and display windows with antigens.*

These Dendritic Cells that are charged up with the snapshot of a battlefield from a virus infection are basically able to call for three different types of reinforcements: They activate the specific Killer T Cells that kill infected cells, and they activate Helper T Cells that help out at the battlefield and Helper T Cells that activate B Cells to provide antibodies. And all that from one Dendritic Cell, which arrived with all the intel and antigens the adaptive immune system could ever wish for.

Killer T Cells need a second signal. As you might imagine, Killer T Cells are a very dangerous bunch that you wouldn’t want to activate by accident.

A Killer T Cell that was activated only by a Dendritic Cell will make a few clones of itself and can fight, but it is a little sluggish and it will kill itself rather quickly.

The second activation signal comes from a Helper T Cell. So this is again the two-factor authentication we got to know with B Cells: To truly activate the strongest weapons of your adaptive immune system both the Innate and the Adaptive immune...

Only if a Helper T Cell has been activated before by a Dendritic Cell and then goes on to restimulate the Killer T

Cell can it live up to its full potential. When truly activated, the Killer T Cell rapidly proliferates and makes lots and lots of clones of itself that eventually move to the battlefield to dish out a lot of death.

About ten days after you caught the infection in the break room you are still pretty sick. Your immune system has been fighting but it also made you feel horrible in the process and the infection is still going strong. Around this time,

insides. If they don’t find antigens they can connect their T Cell receptors to, nothing happens and they move on.

it immediately issues a special command to the cell: “Kill yourself but be very clean about

So instead, the Killer T Cell punctures the infected cell and inserts a special death signal,

Unfortunately there is a huge flaw in this system: Pathogens are not stupid and they found ways to destroy the display windows and therefore hide themselves from the immune system, from Killer T Cells.

Meet the Natural Killer Cell.

Natural Killer Cells are creepy fellows.

Natural Killer Cells hunt two types of enemies: cells infected by viruses and cancer cells.

The Adaptive Immune System is now suddenly harmless to these cells. In a very real way, without their display windows, the infected cells go dark and become impossible to detect. This is quite an effective tactic if you think about it—all a virus or cancer cell needs to do is to stop making a single molecule and boom, the extremely powerful response of the body is helpless.