Tiny Bombs in your Blood - The Complement System

Key Takeaways

every living being needs to fight off for other living beings that want to Feast on them so as multicellular life evolved over billions of years it came up with ways to defend itself today humans have a sophisticated defense network like physical barriers defense cells and weapons factories but one of the most important defenses of our body is largely unknown the compliment system it evolved over 700 million years ago and is an army of over 30 different proteins that work together in a complex and elegant dance to stop Intruders all in all about 15 quintilian of them are saturating every fluid in your body right now Guided by nothing but chemistry these proteins are one of the most effective weapons we have against Invaders many other parts of the immune system are just tools to activate the compliment system but it's also really dangerous imagine having trillions of little bombs inside your blood that could go off at any moment so our cells use numerous mechanisms to prevent compliment from accidentally attacking them okay what exactly does it do and what makes it so [Music] dangerous in a nutshell the compliment system does three things it cripples enemies it activates the immune system and it rips holes in things until they die but how after all these are Mindless proteins randomly drifting around without will or Direction well this is actually part of the strategy compliment proteins float around in a sort of passive mode they do nothing until they get activated and change their shape in the world of proteins your shape determines what you can and cannot do because shape determines what you can interact with and in what way for example in your passive shape you might do nothing in your active shape however you might for example change the shape of other proteins activating them so they can activate others mechanisms like this one can start Cascades that spread very quickly imagine the compliment proteins as being like millions of matches very close together once one catches fire it ignites the ones around it they ignite more and and suddenly you have a big fire to show the actual mechanisms of the compliment system is a tad complicated and overwhelming so we'll simplify here now let's imagine you cut yourself and a bunch of bacteria enter the wound and make it into the surrounding tissue our complement attack begins with C3 C3 is the first match the initial spark that will start our fire and to do that C3 needs to switch from passive to active how this happens is complex but let's just say it can happen randomly through other complement proteins that bind to enemies or through antibodies all you really need to know is that C3 breaks into two smaller proteins c3a and c3b that are now activated one of these parts the c3b protein is like a seea missile specialized in bacteria fungi and viruses it has a fraction of a second to find a victim or it will be neutralized by water molecules if c3b does find a Target it anchors itself very tightly to its surface and doesn't let go by doing so the protein changes its shape again in its new shape it's now able to grab other proteins and start a small Cascade changing its shape multiple times adding other compliment proteins to itself finally it transforms itself into a recruiting platform known as C3 convertis this platform is an expert at activating more C3 proteins that start the whole cycle a new an amplification Loop begins soon thousands of proteins cover the bacteria for the bacteria this is very bad it can the bacteria and make them helpless or slow them down imagine being covered by thousands of flies but there's more do you remember the other part of C3 the c3a protein c3a is like a distress Beacon thousands of them flood away from the sight of battle screaming for attention passive immune cells notice the C3 a proteins and awaken from their Slumber to follow the protein tracks to the site of infection the more alarm proteins they encounter the more aggressive they get this way compliment guides reinforcements exactly to the place where they're needed the most so far the compliment has slowed down the Invaders and called for help now it's beginning to actively help to kill the enemy the first immune cells to arrive at the battlefield are fago sites which means cells that swallow you whole trap you in a tiny prison and then kill you with acid but to swallow an enemy they need to grab it first which is not easy because bacteria prefer not to be grabbed and a sort of slippery but now the compliment that has anchored itself to the bacteria acts as a sort of glue that makes it easy for the immune cells to catch their victims but it gets even better imagine being covered in flies again now imagine them turning into wasps another Cascade is about to begin on the surface of the bacteria the C3 recruitment platform changes its shape again and begins to recruit new proteins together they begin the construction of a bigger structure a membrane attack complex piece by piece new proteins shaped like long Spears anchor themselves deep into the bacteria's membranes until they rip a hole into them that can't be closed again fluids rush into the bacteria and they inside spill out they bleed to death the remaining bacteria are maimed and distracted by the compliment and quickly taken care of by the arriving immune cells The Invasion has been nipped in the bud before it had the opportunity to become dangerous you probably didn't even notice it but while bacteria are not happy about compliment the enemies it might be the most useful against are actually viruses viruses have one problem they need to travel from cell to cell outside of cells they're basically hoping to randomly bump against a cell to infect by pure chance here they're completely defenseless and here compliment is able to intercept and them so they become harmless and guide the immune system to devour them without compliment virus infections would be a lot more deadly but wait if we have such an effective weapon why do we ever get sick the problem is that in a war both sides adapt for example when the vaccinia virus infects a cell it forces it to produce a protein that shuts complement activation down this way the virus creates safe zones around the cells it infects when it kills them and tries to infect more it has a higher chance of being successful or some bacteria for example can grab certain molecules from the blood that keep the compliment system calm and make themselves invisible so the compliment system while being extremely important is only one player in the complex and beautiful organization that is our immune system a beautiful example of how many mindless things can do smart things together