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sponges, the most basic and oldest of all animals, which have existed for more than half a billion years, possess something that probably was the first primitive immune response in animals. It is called humoral immunity.
humoral immunity is very tiny stuff, made out of proteins, that floats through the bodily fluids outside of the cells of an animal. These proteins hurt and kill microorganisms that have no business being there.
Proteins are the most fundamental organic building blocks and tools of all living things on this planet.
DNA is made up of sequences that are building manuals for proteins, which are called Genes.
proteins are so crucial to living beings that the code of life is basically an instruction manual for building them.
To be literally tough, not just figuratively, your skin cells produce a lot of keratin—a very tough protein
When it is warm, humans sweat a lot, which both cools us and also transports a lot of salt to the surface. Most of it is reabsorbed but some of it remains, overall making your skin a pretty salty place, which many microbes don’t like. As if that’s not enough, sweat contains even more natural antibiotics that can passively kill microbes.
Another one of the great passive defenses of your skin is that it is covered in a very fine film of acid, appropriately called the acid mantle, which is a mixture of sweat and other substances secreted by glands below your skin.
Your Innate Immune System reacts immediately. Sentinel cells are the very first to show up—they
These cells are called Macrophages and they are the largest immune cells your body has to offer.
Their purpose is to devour dead cells and living enemies, coordinate defenses, and help heal wounds.
In the blood thousands of Neutrophils have heard the cries for help and smelled the signs of death and begun to move. At the site of infection they leave the rushing ocean of the blood and enter the battlefield. Just like the Macrophages, the panic and alarm signals activated them,
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
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.
it stimulates and squeezes nerve cells that are deeply unhappy about their situation and send pain signals to the brain, which makes the human aware that something is wrong and an injury occurred.
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.
After a few hours of sampling, the Dendritic Cells get on the move, leaving the battlefield behind to get help from the Adaptive Immune System. It takes the Dendritic Cell about a day to reach its destination and when it finds what, or better, who it is looking for, a beast will rouse from its sleep and all hell will break loose.
Macrophage means Great Eater,
The Macrophage is equipped with an abundance of compartments that are filled with the equivalent of stomach acid—substances that dissolve things. These compartments then merge with the tiny prison and pour their deadly contents all over the victim, dissolving it into its components, into amino acids, sugars, and fats that are not only harmless, but even useful. Some become food for the Macrophage
When cells decide their time has come, they release a special signal letting everybody else know that they are done. Then they destroy themselves via apoptosis, which means that they split up into a bunch of small, neat packages of cell garbage. Macrophages, attracted by the signals, pick up the shreds of the former cells and recycle the parts.
In your brain they make up around 15% of all cells and are extra calm, so they don’t accidentally damage irreplaceable nerve cells that you need for important things like thinking about movies or breathing air.
as a battle dies down, some Macrophages turn a battlefield into a friendly construction site and literally begin to eat the remaining soldiers. Then they release chemicals that help the civilian cells regenerate and rebuild damaged structures like blood vessels, so your wounds can heal faster.
Neutrophils are densely packed with granules, which are basically tiny packages filled with a deadly load. You can imagine these granules as little knives and scissors that are made to cut open and cripple intruders. So if a Neutrophil encounters a bunch of bacteria in one place it will just shower them with granules that rip their outsides apart. The problem with this approach is that it is not super specific, and it hits whoever is unlucky enough to be in the way.
But the most mind-boggling thing Neutrophils do in battle is to create deadly nets of DNA, sacrificing themselves in the process.
This is what Neutrophils do when they create a Neutrophil Extracellular Trap.
First their nucleus begins to dissolve, freeing up their DNA. As it fills up the cell, countless proteins and enzymes attach to it—the
And then the Neutrophil literally spits out its entire DNA around itself, like a giant net. Not only can this net trap enemies in place and hurt them—it also creates a physical barrier that makes it harder for bacteria or viruses to escape and move deeper into the body.
The immune system has to assume that cells dying an unnatural death means grave danger, and so death is a signal that causes inflammation.
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.)
cytokines are very small proteins that are used to convey information. There are hundreds of different cytokines and they are important in almost every biological process going on inside of you—from
cytokines are the language of your immune cells.
Let’s say a Macrophage floats around and stumbles over an enemy. The discovery needs to be shared with other immune cell buddies, so it releases cytokines that carry the information
Somewhere else, another immune cell, maybe a Neutrophil, smells these cytokines up and “receives” the information. The more cytokines it picks up, the stronger it reacts to them.
The closer to the origin of the source of a smell a cell is, the more cytokines it will pick up. By measuring the concentration of cytokines in the space around it, it can precisely locate where the message is coming from and then begin moving in that direction.
A signal needs to pass a specific threshold to compel a cell to do something. This is one of the ingenious regulatory mechanisms of your immune system.
If there are too many cytokines the immune system can lose all constraint, become super enraged, and overreact massively—which leads to an appropriately named cytokine storm.
The flood of activating signals wakes up immune cells all over the body, who then might release more. Inflammation rises massively and is no longer limited just to the place of infection. Immune cells flood the affected organs and can cause profound damage. Blood vessels all over the body get leaky and fluid rushes into the tissue and out of the vascular system. In the worst case, the blood pressure will fall to critical levels, and organs will not receive enough oxygen and begin to shut down, which can end deadly.
The chemistry of life causes sequences of interactions between proteins that are called pathways. The activation of pathways causes behavior.
receptors are protein recognition machines that stick in the membranes of cells.
receptors are sort of the sensory organs of cells that let the insides of the cells know what happens on the outside. So if a receptor recognizes a cytokine, it triggers a pathway inside the cell.
When a Macrophage receptor connects to a bacterium protein that fits, two things happen: The Macrophage gets a tight grip on the bacteria and it also triggers a cascade inside the cell that lets it know that it found an enemy and that it should swallow! This basic mechanism is at the core of how your innate immune system knows who is an enemy or not.
Your innate immune system can recognize quite a variety of proteins with a few receptors.
This principle of cells identifying the puzzle pieces of enemies with sort of sensory receptors on their surfaces is called microbial pattern recognition and it will become even more important later on for the adaptive immune system,
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.
Complement proteins are tiny and they are everywhere. Even a virus looks reasonably large next to them.
these are just a lot of mindless proteins, randomly drifting around without will or direction.
the shape of a protein determines what it can and can’t do, what they can interact with, and in what way.
the Macrophages and Neutrophils ordered inflammation, which made the blood vessels release fluid into the battlefield. This fluid carries millions of complement proteins that quickly saturate the wound.
Thousands of C3a flood away from the site of battle, screaming for attention. Passive immune cells like Macrophages or Neutrophils begin smelling them, picking them up with special receptors, and awake from their slumber to follow the protein tracks to the site of infection.
The trail of C3a complement guides them exactly to the place where they are needed the most. In that case, complement does exactly the same job as cytokines,
