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  • Hello and welcome to "Sick Notes"

  • My name is Ed Hope, a junior doctor in the UK

  • And on this channel, we talk about medicine, the human body, hospitals,

  • all types of medical things and explain it in simple terms.

  • Over the last couple weeks, I've been looking at "Cells At Work"

  • I probably would have binge watched the whole season by now.

  • But I've been holding it back because you guys have been really

  • enjoying the review so thank you so much

  • So, let's crack on with episode 3 of "Cells At Work"

  • [Audio from episode clip]

  • So I recognise this chap

  • by his uniform.

  • Uh, this is one of the cytotoxic T cells

  • So you know the soldiers we saw in the early episode.

  • So, before they become these soldiers

  • they have this kind of immature state: why this chap has a cap on

  • that says "NAIVE".

  • So the job of these cells is actually to kill your own cells

  • when they either become infected or damaged.

  • [Audio from episode clip]

  • Hang on a minute, did the-[laughing]

  • did the white blood cell's shoe just fall off there?

  • I'm not quite sure what that's a reference to.

  • Cool, so this is the zombie episode. I've been looking forward to this one.

  • Usually at the start of the scene they tell you what organ you're in.

  • I'm guessing by the fact that we've got these shots of the sewers

  • and that we got an immature T cell here

  • that we're in the lymphatic system of the body.

  • Now, before med school, the lymphatic system

  • used to confuse the hell out of me.

  • And having it as a sewer is a really good analogy.

  • So you imagine all that fluid and nutrients that leak out of the blood vessels

  • to supply your cells. Well, how does that all get collected?

  • Well, it gets collected in a series of ducts

  • called the "lymphatic system", and they drain all the way

  • back up and go back into the bloodstream just above your heart.

  • Because it's a drain-like system, so any bacteria

  • and viruses will also drain into there,

  • so it's a really good place for our immune system to do its work of

  • recognising the bacteria and learning how to fight it.

  • That's why when we get a throat infection

  • you'll feel the glands - the lymph nodes - in your neck swelling up.

  • [#1, 2, 3, 4. We are cells at work.#]

  • [Audio from episode clip]

  • So, as we've predicted in the very first episode,

  • the zombies represent cells infected by a virus.

  • Another really good analogy.

  • I remember my highschool biology teacher asking me:

  • "Are viruses alive or dead?"

  • It was a bit of a trick question

  • because they're neither, because they're never alive in the first place.

  • The only way they can kind of reproduce and grow,

  • some of the things that a living needs to do, is through a host cell.

  • So just like a computer virus on a USB stick

  • it won't just replicate on its own, it needs a computer

  • to replicate that virus.

  • And it's really important to know that bacteria are different to viruses

  • 'cause that's why antibiotics only work on bacterial infections,

  • not viral infections, even though the symptoms may be very similar.

  • [Audio from episode clip]

  • [Laughing]

  • [Audio from episode clip]

  • Wow! Respect to the macrophage!

  • [Audio from episode clip]

  • So, I was waiting for them to show this:

  • You may have noticed throughout the series that whenever a neutrophil destroys

  • a bacteria or a virus, that's it.

  • It just moves on to the next one, whereas the macrophage here

  • is capturing part of the virus so we can identify

  • the virus more easily later and therefore destroy it more easily.

  • The part that it's capturing, we call an "antigen"

  • and for that reason the macrophage is an antigen presenting cell;

  • because it will present this antigen to other immune cells

  • and activate them.

  • For example: it can activate the T cells that we've seen here

  • to turn a naive and immature T cell into a mature cytotoxic T cell.

  • The macrophage is also part of the myeloid family tree that I showed you in the last episode.

  • So let me add it to the gang.

  • So, remember we had this process called "hematopoiesis" - literally meaning: "production of blood"

  • that happens in the bone marrow. So we have our stem cell,

  • our myeloid progenitor cell, of which we can get our red blood cell,

  • our neutrophil,

  • and our megakaryocyte - the ones that produce platelets.

  • Also produced from this sort of family is the macrophage.

  • [Audio from episode clip]

  • This is pretty much what it's like when you first start life as a junior doctor.

  • [Audio from episode clip]

  • Quite a subtle one here, but seeing the neutrophils sort of migrate

  • between the buildings here is a nice little reference

  • probably driven by chemical messengers

  • to see what the immune activity's all about.

  • But we call this process "extravasation",

  • so they're able to sort of squeeze through in-between cells to get to where they need to go.

  • [Audio from episode clip]

  • So we see the infection is spreading quite rapidly.

  • We use the term "incubation period"

  • to describe the amount of time between the initial infection

  • and when symptoms are showing.

  • So this can be anywhere from a couple of days, like influenza - the flu virus we see here,

  • to many years in a virus like HIV.

  • So there's been so much going on in this episode already,

  • I wanted to just explain a couple of concepts that I keep going over.

  • So, the way viruses infect cells,

  • and also how we're able to recognise cells that have been infected by a virus.

  • [#Music#]

  • So here is our cell membrane

  • made up of sort of fatty molecules, that's why I've made it yellow.

  • And we have a nucleus.

  • So our nucleus contains all the genetic material for the whole body,

  • but obviously we only want certain ones for this cell to work.

  • This is our DNA all coiled up like so.

  • So let's just say for argument's sake that this is a cell in the throat;

  • so one of it's jobs is to produce mucus

  • that we saw in the first episode,

  • helps capture bacteria and viruses so we can get rid of them.

  • So let's just say that this cell wants to produce some more machinery

  • that helps produce mucus.

  • So how does this do this?

  • So just part of the DNA that we want will be turned into messenger RNA (mRNA)

  • through something we call the "transcription".

  • It's called messenger RNA because it then travels out into the cell

  • to the ribosomes.

  • So these are gonna represent our ribosomes.

  • So the messenger RNA will travel out of the nucleus

  • to the ribosomes

  • where it will turn the message into proteins, what we call "translations".

  • So in our example these proteins will make a little

  • biological machinery that will create some mucus.

  • So it's important to know that the cell knows what and when to do things

  • by communicating with other cells either directly or through chemicals

  • that interact with these receptors on it's surface.

  • So these receptors here are how the cell communicates.

  • So how to viruses take advantage of this?

  • So this is gonna represent our virus. So kind of in it's simplest form, a virus is

  • this protein capsule, so very different to our lipid membrane

  • that has a piece of genetic material in it.

  • In the case of influenza we have some RNA in.

  • The virus also has some receptors on it's surface.

  • Now, because we talked earlier, the antigens

  • are anything that our body can use to recognise a virus,

  • these are often called "surface antigens"

  • and you can see these surface antigens

  • sticking out on top of the virus in Cells At Work.

  • So, one of these surface antigens may happen to interact

  • with one of the receptors on the end of the cell

  • granting the virus access to the cell.

  • So that's why viruses only infect certain cells

  • so it may just infect a particular species,

  • like a virus that infects dogs might not affect us

  • or specific cells in a species so virus that infects our liver might not affect our skin.

  • In this example, we're using influenza so we know

  • it's got the right receptor to make this handshake

  • this kind of lock and key that can, uh, infect

  • the cells of our respiratory tract.

  • And you may say "Well why do our cells have these receptors if they can be abused like this?"

  • And it's because our cells need to communicate with each other, right?

  • Lots of complex interactions going on.

  • It's sort of like saying

  • "Well why don't you stop your house getting burgled by not having any windows or any doors?"

  • Well, it can't do the job of a house then, can it?

  • So, once inside the cell, the hijack really starts taking place.

  • So the viral genetic material enter the nucleus

  • and hijack our system here.

  • So the mRNA that goes to the ribosomes will be

  • information to produce more viruses...

  • [#Music#]

  • ...that'll then burst out

  • of the cell and infect more cells.

  • [#Music#]

  • So how does your body know that this cell has been infected

  • and know it wants to kill it with the cytotoxic T cells?

  • Well first of all, we saw briefly

  • that the macrophages will break down these viruses and find out these antigens,

  • and so the cytotoxic T cells will be primed to know to look out for these antigens.

  • But currently it can't see any of these antigens on the cell.

  • Well your cell is very clever

  • so it's constantly putting anything from inside the cell onto it's surface.

  • So, as soon as this virus comes in here

  • your cell will put part of the virus

  • on the outside of itself.

  • And that can be anything, it could be the surface antigen,

  • it could be part of the DNA of the virus,

  • it could be part of the virus' capsule.

  • So now your cell is holding up a flag for the cytotoxic T cells

  • by putting parts of the virus on the outside of the cell

  • [Audio from episode clip]

  • Awww. I think we've all been there haven't we,

  • I mean, particularly taking me back to my medical career at med school

  • ...this was... You never feel like you're quite good enough do you.

  • [Audio from episode clip]

  • So we go on this hero journey of discovery with Naive cytotoxic T cell,

  • meeting the dendritic cell,

  • we're getting spoiled for choice with our cells today.

  • So the dendritic cell is also an antigen presenting cell,

  • but it has a much more, kind of powerful, role in stimulating other cells.

  • Again, it's part of our myeloid family, so it would be rude not to add it to our family tree.

  • So here we have our dendritic cell joining it's cousins.

  • There is actually two types of dendritic cell, one that's produced from another route,

  • but we're keeping it simple today!

  • And it's called "dendritic" because dendritic means "tree-like"

  • so it has all these tree-like projections

  • that helps increase it's surface area

  • so it can fit more antigens on it's surface and

  • present more of them to the other immune cells.

  • [Audio from episode clip]

  • So it's a nice little story here, showing the maturation of the Naive T cell

  • after it sees an antigen from the dendritic cell

  • in reality this would happen slightly differently:

  • So if you imagine, all these Naive T cells would have slightly different receptors on them,

  • so it's only the T cell that binds strongly to the antigen on the dendritic cell

  • that will get activated and then proliferate.

  • Kind of like the glass slipper in Cinderella,

  • it has to match perfectly for that T cell to become mature;

  • and that's exactly what you want isn't it?

  • Because you want the T cell that can recognise that antigen the best

  • to be the one that matures and then proliferates

  • because that's the one can recognise the infected cells the best

  • and then kill those cells.

  • [Audio from episode clip]

  • Awww. So, if before his uncertainty was kind of like being a medical student,

  • this is how it feels when you graduate

  • and, you know, you finish your first on call job as a doctor.

  • [Audio from episode clip]

  • So here he is:

  • our newly matured and activated T cell, so he's proliferated as well

  • and he's perfectly designed to target this virus,

  • so I think we're going to see some, uh, the tide turning a little bit on the infection.

  • That's a nice way of saying he's about to smash up some zombies.

  • [Audio from episode clip]

  • [ORA ORA ORA ORA ORA ORA]

  • [OORRRAAAAAA]

  • [Audio from episode clip]

  • Cool, so they talk about why we get a fever in infection as well.

  • So, the reason they think this is because bacteria

  • and viruses typically like lower temperatures to reproduce,

  • I mean, certainly bacteria do because they tend to live on the outside world

  • so when they're in our body, our body increases our temperature.

  • It makes it slightly harder for our own cells, but a lot harder for the bacterial cells.

  • And there's always a debate in medicine:

  • Should you actually treat a fever with medications to bring the temperature down

  • because it's part of the body's defensive mechanism

  • on balance, we do treat it, because it can more likely lead to dehydration,

  • it can make you feel really unwell,

  • and also in children can lead to seizures too.

  • So in the hospital I work at, if someone is running a high temperature

  • we do give them drugs like paracetamol to help lower the temperature.

  • [Audio from episode clip]

  • I like this huge crater we see at the end of the infection,

  • <