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

by Philipp Dettmer

So the Natural Killer Cell just checks for one thing: Does a cell display a window? It does? “Great, please carry on, sir!” It

doesn’t? “Please kill yourself immediately!”

Natural Killer Cells look for the absence of the expected, the absence of self. This principle is called “The Missing-Self Hypothesis.”

Natural Killer Cells are looking for stress, looking for cells that are unwell. Not just during an infection, by the way, right now in this second, millions of these cells patrol your body and check your civilian cells for signs of stress and corruption, cells that are on the verge or have already turned into cancer.

In a sense this is something Natural Killer Cells can do too with your civilian cells. If a cell is under a lot of stress—which in this context means that something is affecting the complex cellular machine,

the cell will express certain stress signals on its membrane.

If Natural Killer Cells detect too many stress signals, they shoot the poor stressed-out cell in the head. So if there were human-size Natural Killer Cells, it would be important to smile a lot around them!

Infected Cells are just not safe from Natural Killer Cells.* OK, now that we have met every major player of your antiviral defense, let us bring them all together!

of Dendritic Cells had sampled the battlefield and picked up viruses, ripping them into pieces that are put into their MHC class I molecules (and their MHC class II molecules). They made their way to the lymph nodes and activated Killer T Cells and Helper T Cells

And now, about a week after you collapsed into bed, your heavy artillery finally arrives.

Millions and millions of Antibodies move in to eliminate the viruses outside of cells and stop them from infecting more cells. Through the magic of the dance of the B and T cells, a number of different types of Antibodies were made that attack the virus on different fronts.

Covered by dozens of Antibodies that block the virus from entering cells, it is now nothing more than a useless and harmless bundle of genetic code and proteins that will eventually be cleaned up by your Macrophages.

them. Antibodies can connect to viral neuraminidase during this budding process and effectively disable it. So you have an infected cell with

Over the next few days the combined symphony of your immune system eradicates the majority of the infection and begins a great cleanup on the battlefield. It seems like the war is already over, but this is not quite true.

So there is an intense need to downregulate the immune response again, to have it strike with just the exact amount of vigor, and to shut it down as soon as it is not needed. To get back to homeostasis.

Well, here we encounter a fundamental problem: viruses are too similar to our own

cells. Wait. What? Well, they are not similar in the sense that a virus is similar to a cell, but in the sense that viruses mimic or work with your own parts.

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

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.

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

although they basically do the same thing, Tetracycline is able to inhibit bacterial ribosomes and not yours.*2

we have thousands of different drugs that can treat viral infections. The only catch is that most of them are pretty

dangerous and sometimes even deadly to us. Many are really more like a desperate last resort, the kind

If you develop a drug that attacks a virus that connects to this receptor it is likely that it will target all the parts of your body that are supposed to connect to the receptor.

A virus is in a perverse way very similar to us because it uses our own parts to make more of itself.

Remember that your mitochondria, the powerhouse of the cell, were ancient bacteria in the past. Because they have kept their own ribosome Tetracycline can also disrupt them, which is not great and leads to pretty unpleasant side effects.

This “winding down” phase is as important as activating your immune system. An active immune system causes collateral damage and uses up a huge amount of energy so your body wants it to be done as soon as possible.

It needs to shut itself down at precisely the correct time, which is easier said than done if you have millions and billions of active cells fighting, without a form of central authority or conscious thought. So as with its activation, your immune system relies on self-enforcing systems to end a defense.

Of course there are exceptions because there is one type of cell that actively switches your defenses off and calms down the immune response: Regulatory T Cells.

Regulatory T Cells are crucial—which makes a lot of sense when you think about

Regulatory T Cells are one of the parts of the immune system where things become very blurry. In

we are still missing the last really important puzzle piece: Your long-term protection, also known as immunity. Why do you get many diseases just once in your life and what does it mean if you become “immune” to anything?

Remembering the enemies it fought in the past and keeping that memory alive is one of the most important abilities of your immune system.

Without immunological memory, you would never become immune to anything,

Memory Cells. Approximately 100 billion living beings, 100 billion parts of YOU, sitting all over your body, doing nothing but remembering what you went through.

Memory cells are one of the main reasons why young children often die of diseases that their parents shake off easily: There are just not enough living memories in their tiny bodies yet, and so even smaller infections can spread and become a mortal danger.

And likewise, as we reach old age, more and more Memory Cells stop working as well as when they were younger or just call it quits, leaving us exposed in the last phase of our lives.

B Cells need two activation signals to truly activate. The first one is delivered by antigen floating through the lymph nodes, and it leads to moderately activated B Cells. But if an activated Helper T Cell joins the party, it can deliver signal number two and confirm that the infection is serious, which activates the B Cell in

earnest. Now the B Cell turns into a Plasma Cell that rapidly makes a lot more of itself and ...

After B Cells are activated through T Cells, some of them will turn into different kinds of Memory Cells! Living memory that will protect you for m...

years. From there they constantly produce a moderate amount of Antibodies. So their entire job is to make sure that specific Antibodies against enemies we fought off in the past are always present in your bodily fluids.

there are also Memory B Cells. They do: Nothing. Nothing at all. Memory B Cells also settle down in your lymph nodes after they are activated, and just chill.

remember. If they ever catch an antigen they awake suddenly and react without any sense of humor. They very rapidly proliferate and make thousands of clones of themselves that don’t need Helper T Cells to properly activate but start as Plasma Cells that immediately begin to produce millions of Antibodies en masse.

your Memory B Cells basically can activate directly, without going through all the complicated dances and confirmations that we showed throughout the book so far. They are shortcuts that can activate your Adaptive Immune System in a heartbeat.

In a similar vein, activated T Cells also produce Memory Cells, although with a few key differences.

10% will turn into Tissue-Resident Memory T Cells, and become silent guardians. These Memory T Cells are dormant sleeper agents, that lie and wait without doing anything. If they ever spot the intruder again they will awaken and attack and activate the surrounding immune cells immediately though.

Effector Memory T Cells. For years they patrol the lymphatic system and your blood, not causing trouble, just looking for

the antigen that once activated the cell that was their ancestor.

Central Memory T Cells, which remain stationary in your lymph nodes, doing nothing but keeping the memory of the attack. When activated they quickly produce massive amounts of new E...

Once your body has memory cells against an invader you are basically immune for decades, if not your whole life.