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  • Sex and not dying.

  • That's what biology is all about.

  • And while the sex part is, I'll grant you,

  • a little bit sexier,

  • not dying is also really fantastic...

  • something that I, personally, like to do every single day.

  • I, personally, like to not die in all sorts of ways.

  • Like, I don't jump out of planes, I don't go into active combat zones,

  • I don't do heroin, but I can, however, spend time wallowing

  • in filth with my cute bacon-producing friends here

  • and not have to worry about dying.

  • Because, somehow, my body can handle a lot

  • of little devils on my hands, in my air, in my food,

  • little things that literally want to kill me.

  • There are more potential human killers in this pig pen

  • than there are in all of the world's prisons,

  • but I don't have to worry about it because of the elite team

  • of microscopic assassins that live inside my body.

  • My immune system.

  • Ahh! That was really close to my hand!

  • You've heard of some of these little ninjas, others maybe not,

  • but everyone knows the work they do by the trail of dead

  • that they leave behind.

  • Pus, being the most disgusting example.

  • And the work these guys do is pretty hardcore.

  • They not only identify incoming enemies, they eliminate them,

  • and then they keep files on them, in case their kind ever comes back.

  • I don't want to freak you out, but you, and I,

  • are covered in pathogens right now.

  • And you really can't blame them for wanting

  • to get a piece of your action.

  • Your warm, high-energy, nutrient- rich, salty, watery action.

  • Your body is a theme park for these guys,

  • and although the majority of organisms living inside you

  • actually make your life more comfy,

  • there are some less-helpful viruses and organisms,

  • from here on out referred to as pathogens,

  • that will want to turn your body into a factory for their children.

  • So let's avoid that!

  • We have two basic ways of doing it:

  • innate, or non-specific, immunity that responds to all kinds

  • of pathogens the same way and very quickly,

  • whether your body has seen that pathogen before or not.

  • And your acquired, or adaptive, immunity which develops

  • more slowly and requires your body to learn the wily ways

  • of the pathogen before it defeats it.

  • Every animal has an innate immune system, even sponges!

  • But only vertebrates have the acquired kind.

  • You were born with your innate immune system.

  • And from the second you wriggled your way out

  • of the sterile environment of your Mom and into this germy,

  • disgusting world, that system has been protecting you.

  • The thing about the innate immune system is that

  • it doesn't care what it's killing.

  • It doesn't worry about whether it's offing a virus

  • or bacteria or fungus.

  • Its job is to just keep the enemy from getting in,

  • or once it's in, to sneak up behind it

  • and break its neck, ninja style.

  • The first line of defense in keeping sketchy characters out

  • are the skin and mucous membranes.

  • The skin has so many excellent functions,

  • like keeping your organs in, that it's easy to forget

  • that its primary purpose is to keep things out.

  • It's oily and kind of acidic, and really not easy to penetrate.

  • And I'm about to rock your world with this,

  • but your digestive tract is also technically the outside of you.

  • Remember how our whole bodies are basically

  • just a built around a tube, right?

  • Well, the inside of that tube is exposed to as much weird,

  • grody stuff as the outside of the tube.

  • So, your body treats the digestive tract like the front lines

  • of this war, which is one of the reasons why your stomach

  • takes no prisoners with the whole stomach acid situation.

  • In addition to things like skin, we've also got mucous membranes

  • providing another barrier to microbes trying to sneak in.

  • Mucus membranes line all of your internal surfaces that are

  • exposed to the outside like your lungs and the inside of your nose,

  • as well as some other parts of your body like the inside

  • of your mouth, and your eyelids and your sex organs.

  • Mucous membranes unsurprisingly produce mucus,

  • which is a viscous fluid, you've probably heard of it,

  • and it traps microbes and helps sweep them away.

  • This is why illness is so often associated with such awe-inspiring

  • amounts of goop.

  • Your second line of defense is your inflammatory response.

  • The honchos here are specialized cells in your connective tissue

  • called mast cells that constantly search for suspicious objects,

  • usually unknown proteins, and then release signaling molecules,

  • like histamine when they find them.

  • Histamine makes your blood vessels more permeable,

  • which allows a whole bunch of fluid to flow to the affected area.

  • And that is what causes inflammation,

  • but it also brings in a crap-ton of white-blood cells,

  • infection-fighters, to go all Balrog on whatever's

  • trying to make its way in.

  • Now, this is great if you get a splinter in your toe

  • or a bunch of viruses in your face,

  • but sometimes something gets into you that's not actually dangerous

  • like pollen or dust or, like, a peanut

  • and your innate immune system triggers

  • an inflammatory response anyway, even though it's not a big deal.

  • This is what we call an allergic reaction,

  • and you know what those are like

  • with the swelling, redness, mucus production, itching,

  • and occasionally a little bit of death.

  • So that is why we take antihistamines to suppress

  • the histamine trigger so our immune systems stop freaking out

  • about nothing, also, that is why you should always

  • tell people when there are peanuts in your cookies.

  • Most of the immune system activity that happens inside

  • your body's fortress is done by white blood cells, or leukocytes.

  • Leukocytes are awesome for a lot of reasons,

  • but one reason is they've got full VIP access to anywhere

  • in the body that they want to go, with the exception

  • of the central nervous system: the brain and spinal cord,

  • which are, for obvious reasons, super high security areas.

  • Leukocytes can move through the circulatory system

  • and when they get to a place where they're needed,

  • they can basically send a signal to ask the capillary

  • to open a gap between it's cells and then it oozes through that gap

  • to the site of the infection, this is called,

  • get ready for it, diapedesis.

  • From the greek for "oozing through."

  • There are lot of different kinds of leukocytes,

  • like different branches of your own personal microscopic army.

  • The kind specific to the innate immune system are phagocytes,

  • more greek, this time Phago, meaning eating.

  • And they're just any cells that ingest microorganisms

  • through the process of phagocytosis.

  • Phagocytes are pretty cool.

  • They can literally chase down the invading cells,

  • grab them and then completely engulf them.

  • And some, like the super-abundant neutrophils,

  • move around the bloodstream, and can quickly get

  • to where the action is.

  • Once a neutrophil kills an invading microbe,

  • they basically just roll over and die.

  • Dead neutrophils collect together into what we lovingly call pus.

  • The biggest and baddest of the phagocytes are the macrophages,

  • the "big eaters," which don't generally travel a lot,

  • but instead hang out like bodyguards in your various organs.

  • Not only do they kill outside invaders,

  • they can also detect when one of your cells has gone rogue,

  • like a cancer cell, and kill those, too.

  • And they, unlike the neutrophils, don't die once they've

  • killed a bacterium.

  • They can eat up to 100 before they die.

  • BIG EATER!

  • Of all the grisly stuff that goes on in the never-ending

  • street war that is your immune system, some of the most

  • gruesome stuff is done by a kind of cell called

  • "Natural Killer Cells" which reminds me,

  • I think it's time for our very first Open Letter.

  • An open letter, to 1973.

  • Dear 1973,

  • You had a lot going on, the Vietnam war ending, Roe v Wade,

  • Watergate...it was a tumultuous time.

  • But part of me wishes that you, 1973, had an opportunity

  • to name everything in biology because you got one chance

  • to name a new type of immune cell, and you named it

  • "The Natural Killer Cell" and I freaking love that.

  • I look around at today's script with all of it's dendritic cells

  • and macrophages and dieapudeesises and I think,

  • what if we let 1973 name all these things,

  • would we have Spikey Death Cells, Devourerers,

  • and Oozing Action instead?

  • I don't know...maybe you would have screwed it up,

  • but I don't think you could have done any worse

  • than all of this GD greek we have to deal with all the time.

  • Thanks for the Endangered Species Act! - Hank

  • Ok! Natural Killer Cells, more than just a great name,

  • also the only phagocyte in the innate immune system

  • that destroys other human cells.

  • When your cells are healthy, they have a special protein

  • on their surface called MHC I

  • MHC for major histocompatability complex.

  • But when your cells are infected, say with a virus,

  • or when they're cancerous, they stop producing that protein.

  • So the Natural Killers are always going around checking up

  • on each of your cells, and when it finds one that's not normal,

  • it pulls out it's AK47 and unloads.

  • Actually, it just binds with it and then secretes

  • an enzyme that dissolves its membrane, but still. Killing.

  • Finally, dendritic cells are a type of phagocyte

  • that hangs out on the surface of much of your body

  • that comes in contact with the environment

  • in your nose, on your skin, in your stomach and intestines.

  • They eat up pathogens and then carry information about them

  • back to the spleen or lymph nodes, where it passes intelligence

  • about what's going on on the war front to the acquired immune system.

  • I actually studied dendritic cells in my undergraduate thesis

  • and I kinda fell in love with them.

  • They're lethal... but they're also intelligent,

  • great heroes for any Robert Ludlum novel.

  • To be fair though, macrophages can do this too.

  • The activity of these cells give us a chance to transfer

  • from the innate immune system to the acquired immune system,

  • which is going to make things a little more complicated.

  • The acquired system has to learn as much as it can about every

  • pathogen it interacts with, store that information,

  • and then use it to invent defenses against them.

  • It's your super-elite, double-secret strike force delta.

  • You get to work building your acquired immune system

  • immediately after you're born, harvesting bacteria and other stuff

  • not just good bacteria that can help your guts out,

  • but also harmful ones that your body learns from

  • and stores information about.

  • That system keeps an eye out for any foreign substance:

  • a toxin, a virus, a bacteria, even parts of those things

  • that could be tell-tale signs of a bad guy.

  • We call those signs antigens,

  • a word that comes from antibody generator.

  • An antigen is anything that causes your immune system

  • to ID a pathogen and then create an antibody against it.

  • Now antibodies aren't cells, they're highly specialized

  • proteins produced by B cells to recognize and help lay

  • the smack-down on intruders.

  • But antibodies can't kill invaders themselves.

  • They're just little proteins after all.

  • The best that they can do by themselves is just swarm all over

  • the invader, making it harder for it to move,

  • and to excrete toxins, or otherwise infiltrate healthy cells.

  • But more often, antibodies serve as "tags,"

  • attaching themselves to the scumbags and then releasing

  • chemical signals to nearby phagocytes,

  • alerting them that it's dinner time.

  • Your acquired immune system also has its own type

  • of white blood cells.

  • Not phagocytes, which go after everything that looks

  • a little bit sketchy, but lymphocytes, which go after

  • specific things that they already know about.

  • There are two major types of lymphocytes:

  • the T cells, which form in your bone marrow

  • and migrate and mature in the thymus gland,

  • behind your breastbone, and B cells,

  • which originate and mature in the bone marrow.

  • What T and B actually stand for is a long story,

  • but if it helps you to remember:

  • T's mature in the thymus, B's in the bone marrow.

  • We have two different types of lymphocytes because our bodies

  • have two different types of acquired immunity,

  • the cell-mediated response which is for when the cells are

  • already infected, and the humoral response,

  • for when the infection is just in the humors,

  • the body's fluid, not in the cells.

  • First, let's look at the cell-mediated response.

  • This process mainly involves T cells,

  • and there are quite a number of different types of them.

  • Helper T cells have a cute-sounding name,

  • but in a lot of ways they call the shots for the whole immune system.

  • While they can't kill pathogens themselves,

  • they activate and direct the cells that can.

  • If 1973 had named them, they might have been called

  • "Admiral T Cells" or something more awesome.

  • Helper T cells get their information from other immune cells

  • that are out cracking skulls.

  • Say, for instance, a macrophage finds a pathogen and destroys it.

  • After the deed has been done, it has the ability

  • to shred up the proteins from an invader,

  • and put a bit of that antigen on its membrane surface.

  • This is called antigen-presentation because the cell is...

  • presenting antigens!

  • A helper T-cell can detect when this happens and it comes over

  • to attach itself to the presented antigen.

  • The two cells talk to each other chemically.

  • The antigen presenting cell produces a chemical called Interleukin 1

  • which basically tells the Helper T cell,

  • "Uh, boss, I found this guy over here and then I broke his neck

  • and then I stuck his guts all over my cell wall."

  • And the Helper T cell gives it a look and then releases a chemical

  • called Interleukin 2, which is like a bullhorn,

  • an alarm that tells all the lymphocytes in the area,

  • "THERE ARE PROBLEMS HERE!

  • WE'VE GOT A PROBLEM OVER HERE IN SECTOR 15!"

  • This alarm activates a couple of different things all at once:

  • First, the Helper T cell starts making copies,

  • tons of copies, of itself.

  • Most of those copies differentiate into effector T cells,

  • which travel around secreting signaling proteins

  • that stimulate other nearby lymphocytes to take action.

  • Most of the rest of them become memory T cells.

  • They're the ones that keep a record of the intruder

  • and provide us with future immunity against it.

  • And now for the saddest story of the day.

  • What happens when a cell gets infected.

  • SO infected that it knows that it's a goner,

  • that it, in fact, is being converted from a healthy,

  • useful part of the body, to an evil zombie farm,

  • pumping out viruses or bacteria, suddenly co-opted

  • to help destroy everything it loves?

  • Well, with its last bit of strength, it'll start

  • presenting antigens, not asking to be rescued,

  • but instead asking for a mercy killing.

  • The cytotoxic T cell has the job of granting that request.

  • Once a cytotoxic T cell gets the message from the helper T cells

  • that there's an infection to deal with,

  • it starts patrolling the area for normal cells presenting antigens.

  • When it finds one, it latches onto it and releases enzymes

  • that create holes in the cell's membrane and eventually

  • breaks down the whole cell, killing the cell and the pathogen

  • in the process.

  • A human cell killing another human cell.

  • Now for the Humoral Response.

  • The humoral response is designed to catch pathogens

  • that are floating around in your body that haven't

  • actually invaded any of your cells yet.

  • The primary players are B cells,

  • which are constantly patrolling your bloodstream

  • like cops walking the beat until they get a signal

  • from a Helper T cell that something's wrong.

  • B cells are covered in antibodies that can detect

  • and bind to a specific antigen.

  • A single B cell can be covered in a forest of up to 100,000

  • antibodies, say, for the virus that causes the common cold,

  • and the B cell next to it will have just as many receptors

  • for a different antigen, for chicken pox or something.

  • When a B cell bumps into a pathogen that it recognizes,

  • it attaches to it and starts cloning itself like crazy.

  • Suddenly there are tons of that B cell with the same receptor

  • but during the cloning process, the clones differentiate

  • into new versions of the original just like the T Cells did.

  • Most turn into plasma or effector cells,

  • which use the antibody as a blueprint to creating a crap-ton

  • of antibodies for that specific pathogen

  • like 200 antibodies per second!

  • Once these antibodies are released, they bind to the pathogens

  • like crazy, marking them for death until a phagocyte

  • can come along and do the dirty work.

  • The rest of the cloned B cells mostly become memory cells,

  • which have the same receptor and stick around,

  • providing future immunity from this invader.

  • And we are now very out of time, but I really love this stuff,

  • so I didn't want to gloss over anything.

  • Mucus, natural killer cells, macrophages killing things,

  • breaking them up and sticking them on their cell membranes,

  • effector cells spewing out antibodies, and memory cells,

  • making sure that our immune systems hold that grudge,

  • all because my absolute favorite thing to do

  • every single day is not die.

  • If you want to review anything we discussed in this episode

  • there's a table of contents over there.

  • If you have any questions for us,

  • we'll be down in the comments or on Facebook or Twitter.

  • And we'll see you next time.

Sex and not dying.

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あなたの免疫システム自然に生まれたキラー - クラッシュコース生物学#32 (Your Immune System: Natural Born Killer - Crash Course Biology #32)

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    Chi-feng Liu に公開 2021 年 01 月 14 日
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