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

by Philipp Dettmer

And what are animals really to a bacteria and other critters if not a very nice ecosystem? An ecosystem filled top to bottom with free nutrients. So from the very start intruders and parasites were an existential danger to the existence of multicellular life.

At its very core, the immune system is a tool to distinguish the other from the self.

The goal above all things is maintaining and establishing homeostasis: the equilibrium between all the elements and cells in the body.

Your Immune System consists of two major realms: Innate and Adaptive Immunity. Your Innate Immune System is ready to fight after birth, and can identify if an enemy is not self, but other. It does the down-and-dirty hand-to-hand combat, but it also determines what broad category your enemies fall in and how dangerous they are. And finally it has the power to activate your second line of defense: Your Adaptive Immune System, which needs a few years before it is ready to deploy efficiently. It is specific and can draw from an incredibly large library to fight every possible individual enemy that nature can throw at it, with powerful superweapons. But while it is powerful, one of its most important jobs is to make the Innate Immune System even stronger.

Up to fifty layers of dead cells, fused together on top of each other, form the dead part of your skin that ideally covers your whole body.

The acid mantle is not so harsh that it would hurt you, it just means that the pH of your skin is slightly low and therefore slightly acidic and that is something a lot of microorganisms don’t like.

The cells fighting at the site of infection started a crucial defense process: Inflammation. This means they ordered your blood vessels to open up and let warm fluid stream into the battlefield, like a dam opening up towards a valley.

Macrophages probably are an extremely old invention of the immune system, maybe even the first sort of dedicated defense cell, since almost all multicellular animals have some form of macrophage-like cell. In a sense they are a bit like single-celled organisms. Their main job is border patrol and garbage disposal unit, but they also help with coordination of other cells, preparing the battlefield by causing inflammation, and encouraging wound healing after an injury.

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

In a nutshell, 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!

According to pretty new science, 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.

These noses are so sensitive that for some cells, as little a concentration difference as 1% in the cytokine signals around a cell is enough to tell it where to go.

An antigen is a piece of an enemy that your immune system can recognize.

For every possible antigen that is possible in the universe, you have the potential to recognize it inside you right now.

an autoimmune disease is your adaptive immune system thinking that your own cells are enemies, that they are other.

our adaptive immune system has the largest library in the universe. We learned that after they are born, your T Cells rearrange a few select gene fragments to create billions of different receptors (each T Cell carries only one receptor type). And that in total these many different T Cells, each with its own unique receptor, are able to recognize every possible antigen in the universe. To make sure your own adaptive immune cells do not accidentally recognize and attack your own body, these T Cells have to undergo a rigorous training that only a tiny minority survives. But in the end you get a few immune cells for every possible enemy that could ever infect you.

To activate your Adaptive Immune System, a Dendritic Cell needs to kill enemies and rip them into pieces called antigens, which you can imagine as wieners. These antigens are put into special molecules, called MHC class II molecules, that you can imagine like hot dog buns. On the other end, Helper T Cells rearrange gene segments to create a single specific receptor that is able to connect to one specific antigen (a specific wiener). The Dendritic Cell is looking for just the right Helper T Cell that can bind its specific receptor to the antigen. And if a matching T Cell is found the two cells interlock. But then there needs to be a second signal, like a gentle encouraging kiss on the cheek, that tells the T Cell that all is good and the signal from the presented antigen is real. And only then does a Helper T Cell activate.

You find potential partners with MHC molecules that are different from yours more attractive! OK wait, what? How would you even know this? Well, you can literally smell the difference! The shape of your MHC molecules does influence a number of special molecules that are secreted by your body—which we pick up subconsciously, from the body odor of other people—so

An organ that is transplanted had to be taken out of another living being—to do that it had to be separated from it. Usually with sharp tools. This whole process is likely to have caused small wounds—what do wounds inside the body trigger? Inflammation, which then attracts the Innate Immune System. And if things go wrong, the Adaptive Immune System gets called right to the edges of the new life-saving organ and can call in more cells that check out the display windows only to find that they are not yours. 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. To minimize the chance that your immune cells find the foreign MHC class I molecules and kill the cells carrying them. But of course this will leave you much, much more vulnerable to infections.

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.

A good drug is basically a molecule that connects to the specific shape of a part of an enemy (not too dissimilar to an antigen and a receptor!) that is not present in your body. In principle, this is how many drugs and antibiotics work. They attack a difference in shape between bacterial and human parts.

Activation usually begins with an initial exposure of immune cells to intruders, like bacteria, or danger signals, like the insides of dead cells. For example, Macrophages get activated when they notice an enemy and release cytokines that call up Neutrophils and cause inflammation. The Neutrophils themselves release more Cytokines, causing more inflammation and reactivating Macrophages, who continue fighting. Complement proteins stream into the site of infection from the blood, attack pathogens, opsonize them, and help the soldier cells to swallow the enemies. Dendritic Cells sample enemies and make their way to the Lymph Nodes to activate Helper T Cells or Killer T Cells, or both. Helper T Cells stimulate the innate immune soldiers to continue fighting and create more inflammation. Killer T Cells start killing infected civilian cells with support from Natural Killer Cells. Meanwhile, activated B Cells have turned into Plasma Cells and release millions of Antibodies that stream onto the battlefield and disable the pathogens, maiming them and making them much easier to clear up. This is the immune response in a nutshell.

Long-Lived Plasma Cells who wander into your bone marrow and as their very creative name suggests, they live pretty long. Instead of vomiting out as many Antibodies as they can, they make themselves comfortable and find a home where they will stay for months and 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. If the enemy shows up ever again, it will immediately get attacked by these antibodies and probably has no chance to become a real danger again.

masse. This is the reason why you are immune forever against so many diseases and pathogens you encountered in your life—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.

But there is a vicious part of measles that is not discussed as much as the disease itself: Kids who overcome a measles infection have a higher chance of getting other diseases afterwards because the measles virus kills Memory Cells. If you think that sounds a bit scary, that is the correct reaction—the virus basically deletes your acquired immunity.

So let us summarize the tactic of HIV real quick before we move on: By infecting Dendritic Cells, the virus gets a taxi into HIV heaven: The lymph nodes, which are filled top to bottom with Helper T Cells. HIV can build reservoirs in these cells and stay hidden indefinitely. When Helper T Cells begin to proliferate massively, they do so at lymph nodes, which is the ideal place for HIV to also make millions of new viruses. So the place that is most central to building protection against viruses is completely taken over and actually becomes a weak point.

The microorganisms that are causing infectious diseases are comparatively new to our biology.

So it seems growing up in a less-urban environment offers some protection against allergic disorders.

As every generation moved a bit farther away from the natural environment their microbiomes became less diverse and their children inherited their microbiome. Over time the average diversity of the microbiome in developed countries seems to have fallen considerably, especially compared to humans still living a more traditional and rural lifestyle.

So what can you take away from this chapter? Wash your hands at least every time you use the restroom, clean your apartment but don’t try to sterilize it, and clean the tools you use to prepare food properly. But let your kids play in the forest.

Boosting the Immune System is a horrible idea that is used by people trying to make you buy useless stuff!

Even the mere term “strong immune system” is a misnomer. Over everything else, you want a balanced immune system. Homeostasis. Aggression and calmness.

But if you eat at least somewhat of a balanced diet with some fruits and vegetables, you will get all the micro and macronutrients for your immune system to work just fine.