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

by Philipp Dettmer

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.

Great summary!

As more and more enemies are killed and their numbers are dwindling, fewer and fewer battle cytokines are released, because fewer immune cells are stimulated by ongoing fights. This means no more new soldiers are called in while the old ones die off or stop fighting. The cytokines that cause inflammation are used up relatively quickly, so without new and engaged soldiers that constantly release new cytokines, the inflammation reactions begin receding naturally, which also slowly has the complement system fizzle out. Fewer signals from the battlefield means that the activation of new T Cells first slows down and then stops, while active T Cells become harder to stimulate the longer they are active, until eventually most of them kill themselves. No part of your immune system is made to work forever without stimulation and so if the chain of activations stops, step-by-step, the immune response winds down. In the end your Macrophages devour and clean up the carcasses of the brave immune cells that fought so hard to eradicate the infection to protect you. And so, just as your immune system is winning, it is already shutting itself off without any sort of central planning. 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. They make up only about 5% of T Cells and in a sense are “opposite Helper T Cells.” For example they can order Dendritic Cells to become worse at act...

To artificially induce the creation of Memory Cells that stick around for years, we need to activate your immune system for real. And this means it has to go through the proper steps of escalation. Two-factor authentication and all of that jazz. So we must somehow safely provoke a proper immune response but avoid causing the actual disease we want to protect ourselves against. There are a few different ways to do this. The first method basically comes back to the original principle of variolation. What if we could sort of cause the disease we want to immunize against, but just a really, really weak version of it? This is the principle of live-attenuated vaccines, where we put the real thing into our bodies, but a weak version of it. The original pathogen, like a chicken pox, measles, or mumps virus, is artificially made into a pathetic shadow of itself in a laboratory. This works especially well with viruses because, in contrast to pathogens like bacteria, they are just really simple creatures with only a handful of genes, making it easier to control how well they work. The mechanism of how live viruses are weakened is pretty interesting because it is literally using evolution. A little bit how the ancestors of dogs used to be majestic and powerful wolves that we turned into pugs and Italian greyhounds. In the case of the measles virus, for example, the virus that we use for vaccines today was isolated from a kid in the 1950s. It was cultured over and over and over again i...

upgrade their immune system and protect them against the target of the vaccine for the remainder of their lives. Using living pathogens is not always an option though. Just like you can’t domesticate great white sharks, some pathogens refuse to be tamed and become properly weak. In some cases the risk of them causing the disease we want to protect against is just too high. So another method is to straight up kill the pathogen before injecting it, which is called an inactivated vaccine. You get a high number of the pathogenic bacteria or viruses together and then you destroy them with chemicals, heat, or even radiation. The goal is to destroy their genetic code so they are empty and dead husks, unable to reproduce and go through their life cycles. But this also creates a problem. Can you imagine what? They are too harmless now! Your immune system will not be properly provoked by a bunch of carcasses of pathogens that just float around and are pretty dead. So the dead remains of the pathogens have to be mixed with chemicals that highly activate the immune system. You can imagine these chemicals like insults that provoke a disproportionate response, like running around wearing the jersey of the opposing team and insulting the home team in a city that just has lost a major sporting event. Chances are at some point someone will punch you in the face. If dead bacteria are mixed with substances that really put the immune system on edge, your immune cells will not be able to make ...

If you read this far you already know more about immunology than 99% of the general population.

Beware headlines about anything health related that mentions animal models. Yes, it is crucially important to test drugs in animals, but unsurprisingly, animals and humans are different. Yes, we have created mice with immune systems that basically mirror our human immune system, yes, we have monkeys like macaques that live on an evolutionary branch that is not that far away from ours, but these are still completely different organisms.

Important!