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

by Philipp Dettmer

Proteins are made from chains of amino acids, which are tiny organic building blocks that come in twenty different varieties. All you need to do is to string them together into a chain, in whatever order you like, and voila, you have a protein. This principle enables life to construct a stunning variety of different things. For example, if you wanted to make a simple protein from a chain of ten amino acids, and you have twenty different amino acid types that you can choose from, this gives you a breathtaking 10,240,000,000,000 different possible proteins.

Your DNA, a long sequence of instructions that are necessary for a living thing to be a living thing. What this means in this context is that around 1% of the DNA is made up of sequences that are building manuals for proteins, which are called Genes. The rest of your DNA is regulating which proteins are built when and how and how many of them at which time.

Genes: the manual that describes recipes

Special proteins read the information on the DNA string and convert it into a special messenger molecule called mRNA—basically the language that our DNA uses to communicate orders.

Everybody is pushing around and is getting pushed. This process is called Brownian motion and it describes the random movement of molecules in a gas or fluid.

Pathways are fancy words to describe a series of interactions between individual things that lead to a change in a cell.

Cells are filled up by proteins. Proteins are three-dimensional puzzle pieces. Their specific shapes enable them to fit together or interact with other proteins in specific ways. Sequences of these interactions, called pathways, cause cells to do things. This is what we mean when we say that cells are protein robots guided by biochemistry. The complex interactions between dumb and dead proteins create a less dumb and less dead cell, and the complex interactions between slightly dumb cells create the pretty smart immune system.

This phenomenon occurs all over nature, and is called emergence. It is the observation that entities have properties and abilities that their parts do not have.

The Realm of the Innate Immune System contains all the defenses you are born with and that can be employed mere seconds

The Realm of the Adaptive Immune System contains specialized super cells that coordinate and support your first line of defense. It contains factories that produce heavy protein weapons and special cells that hunt and kill infected body cells in the case of viral infections. Its defining feature is that it is specific.

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.

There are a number of ingenious strategies the kingdom uses to be almost impossible to overcome for an intruder. The first one is that it is constantly dying. You can imagine your skin less as a wall and more like a conveyor belt of death.

Sentinel cells are the very first to show up—they were peacefully patrolling the premises when the impact happened and are quickly making their way right to ground zero, attracted by the screams and the detritus of the crash site. These cells are called Macrophages and they are the largest immune cells your body has to offer. Physically, Macrophages are pretty impressive.

Platelets, blood cells that exist mainly to act as an emergency worker that closes wounds. They produce a sort of large, sticky net that clumps themselves and unlucky red blood cells together and creates an emergency barrier to the outside world, stopping blood loss rather quickly and preventing more intruders from entering. This enables fresh skin cells to slowly start closing the enormous hole in the world.*

The cells fighting at the site of infection started a crucial defense process: Inflammation.

The Dendritic Cell, the mighty messenger and intelligence officer of the Innate Immune System did not just watch the disaster unfold. Dendritic Cells are stationed everywhere the Border Kingdom can be penetrated. Shaken up by the chaos and panic, they urgently began collecting samples of the battlefield.

Macrophages and Neutrophils are the damage dealers of the Immune system. Together they are a special class of cells called phagocytes.

So every second of your life, around one million of your cells die by controlled cell suicide, called apoptosis (this process will come up a few times in this book because it is very important). When cells decide their time has come, they release a special signal letting everybody else know that they are done.

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

Mast Cells are large, bloated cells filled with tiny bombs containing extremely potent chemicals that cause rapid and massive local inflammation. (For example, the itching you feel when a mosquito bites you was probably caused by chemicals the Mast Cell released.)

For cells, information is a physical thing: Cytokines. In a nutshell, cytokines are very small proteins that are used to convey information.

The chemistry of life causes sequences of interactions between proteins that are called pathways. The activation of pathways causes behavior. In the case of cytokines, the information protein of the immune system, this happens through pathways that involve special structures called receptors on cell surfaces. They are the noses of your cells.

In a nutshell, receptors are protein recognition machines that stick in the membranes of cells.

The immune system of all animals has some variant of Toll-Like Receptors, which makes it one of the oldest parts of the immune system that evolved probably more than half a billion years ago. Some toll-like receptors can recognize the shape of flagella, others certain nooks and crannies on viruses, others again telltale signs of danger and chaos, like free-floating DNA.

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

The complement system is one of the oldest parts of your immune system,

In a sense, it is the most basic form of any animal’s immune response, but it is also very effective.

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.

In a nutshell, the complement system does three things:

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.

V v imp

First your black rhinos, Macrophages, huge cells that swallow enemies whole, appear and dish out death. If they sense too many enemies they use cytokines, information proteins to call your chimp-with-machine-gun Neutrophils, the crazy suicide warriors of the immune system. Neutrophils don’t live long and their fighting is harmful to the body because they kill civilian cells. Both of these cells cause inflammation, bringing in fluid and reinforcements to an infection, making a battlefield swell up. One of the reinforcements is complement proteins, an army of millions of tiny proteins that passively support the immune cells in their fight and help mark, attach to, maim, and clear enemies. These powerful teams together are enough for most small wounds and infections you encounter.

they have two of the most crucial jobs of your entire immune system: They identify what kind of enemy is infecting you, if it is a bacterium or a virus or a parasite. And they make the decision to activate the next stage of your defense: Your adaptive immune cells, your heavy, specialized weapons that need to come in if your innate immune system is in danger of being overwhelmed.

Your network of lymphatic vessels is miles long and covers your entire body. It is a sort of partner system to your blood vessels and blood. The main job of your blood is to carry resources like oxygen to every cell in the body and to do that, some of the blood needs to actually leave your blood vessels and drain into your tissue and organs to deliver the goods directly to your cells.

Monocytes are basically reinforcement cells that can transform into Macrophages and Dendritic Cells. About half of them patrol in your blood right now where they represent the largest single cell that floats through your cardiovascular system. If you suffer an injury and an infection that drains and kills a lot of your Macrophages, they come in as backup.

Your Innate Immune System is able to recognize some of the common protein puzzle pieces our enemies use with those special receptors we discussed called Toll-Like Receptors.

a protein piece that is recognized by the immune system is called an antigen.

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

So through controlled recombination, your immune system is prepared for every possible antigen an enemy could make.

Without T Cells you are quite dead—they may be the most important Adaptive Immune Cell you have. But before they can fight for you, they need to pass the horribly dangerous curriculum in the Thymus.

The adaptive immune system is mixing gene segments to produce an amazing variety of different receptors, able to connect to every possible protein, in this context called an antigen, in the universe. This means that each individual T Cell is born with ONE specific type of receptor, able to recognize ONE specific antigen.

The first test is basically just making sure the T Cells have the ability to make working T Cell receptors.

The second test is called positive selection: Here the teacher cells check if the T Cells are really good at recognizing the receptors of the cells they will need to work with.

Negative selection. And this might be the hardest test of all. The final exam is simply: Can the T Cell recognize self? Can its receptor connect to the main proteins inside the body? The proteins that make you, you? The only acceptable answer is “No, not at all.”

Let us summarize one last time because this stuff is really important and really hard: 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.

Clonal Selection Theory.

Your activated T Cell leaves the Dendritic Cell that activated it behind and wanders to a different part of the Lymph Node City where it begins the process of cloning itself. It divides over and over again, multiplying as fast as it can. One activated Helper T Cell becomes two, two become four, four become eight, and so on. Within hours there are thousands of them.

Some Helper T Cells become Memory Helper T Cells. Whenever you hear that you are immune to a disease, this is what this means. It means that you have living memory cells that remember a specific enemy.

What makes B Cells special, and very dangerous for friends and foes, is that they produce the most potent and specialized weapon the immune system has at its disposal: Antibodies.

Antibodies are basically B Cell receptors.

Virgin B Cells sit in your lymph nodes, where they bathe in lymph and take in all the antigens that are transported through the area from the closest battlefield. Their B Cell Receptors can just grab big chunks of antigens directly from the lymph and this way B Cells can get activated.