Cytotoxic T Cells How cytotoxic T cells get activated by MHC-I/antigen complexes and then proceed to kill infected cells
Cytotoxic T Cells
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- When we learned about antigen presenting cells, we learned
- that they can first digest something-- let me draw a
- dendritic cell right here-- my best version
- of a dendritic cell.
- Maybe I should draw them simpler than that.
- A dendritic cell is a phagocyte and it is an antigen
- presenting cell.
- So after phagocytoses some type of a pathogen, it'll cut
- it all up, and then it'll display-- it'll present the
- antigen on its surface on a protein complex here and the
- part of the pathogen that it cut up, it'll
- put up right here.
- And we learned on the antigen presenting cell video that
- this complex right here was an MHC type II complex, where MHC
- stands for major histocompatibility complex.
- Where histocompatibility just means tissue compatibility.
- And this was the case on antigen presenting cells.
- So even B cells did this.
- Let me draw a B cell.
- So a B cell-- it has its membrane bound
- antibody, just like that.
- It actually has many, many thousands of these.
- I could keep drawing a bunch of them, but just so you know
- there's more than one.
- Maybe one of these get triggered or get attached to
- some type of virus or protein or bacteria floating around.
- And what it'll do is it'll take this in and cut it up
- again and do the same thing as what the dendritic cell did.
- It'll cut up a part of this and present it on its surface
- in conjunction with an MHC II complex.
- So once again, this is an MHC II complex.
- So these professional antigen presenting cells that go out
- and take things out of the fluid, out of the humoral
- parts of our body, things just floating around.
- They'll take them in, they'll say, this is bad, cut them up,
- and then present them on these MHC II.
- That's why we call them professional antigen
- presenting cells.
- Now, it turns out that pretty much all cells in our bodies--
- when I say almost all cells, it's actually
- all nucleated cells.
- So all cells that have a nucleus in the human body-- so
- the only cells in our human body that don't have nucleuses
- are red blood cells, which I find fascinating-- so that
- they can have more space for storing hemoglobin.
- But all nucleated cells in our bodies have another major
- histocompatibility complex on it and it's called an MHC I--
- major histocompatibility type I.
- And just so you know, these are also nucleated cells.
- So they're also going to have an MHC type I complex on them
- right here.
- Now the interesting thing about the MHC type I complex
- is because it's on every cell in our human body-- so pretty
- much everything but the red blood cells have an MHC I--
- this is where if anything wacky is going
- on inside the cell.
- Maybe the cell is cancerous and producing crazy proteins.
- Maybe it's been infected with a virus.
- Maybe some type of bacteria or some type of weird protein has
- gotten in here-- any cell in the human body can cut those
- up, even if it's malfunctioning, and it will
- present them.
- So let's say the cell is cancerous.
- So this cell's cancerous and it has all these wacky
- proteins that only cancer cells present that is not
- normal for a normal cell-- that will be
- presented on the MHC I.
- Let's say that I have some other cell in my body that's a
- different type of cell.
- It's nucleated.
- Let's say it's been infected with a virus.
- So it's turning into this virus factory.
- Same thing-- there are mechanisms in a cell that will
- take some of the proteins that make up those viruses and
- present them on the MHC I complex.
- So in the case of MHC II, this is what triggered helper T
- cells to say, hey, you know what?
- I found something floating out here.
- Here's a little piece of it, Mr. Helper T cell.
- Why don't you bond to this and raise the alarm system?
- Now the MHC I system says, this isn't
- stuff floating around.
- I've been infected.
- I am cancerous.
- I'm going nuts.
- You better kill me.
- I'm a virus, I'm a virus-making machine.
- You better kill me.
- And that message goes to the cytotoxic T cells and that's
- really the topic of this video.
- So just to make sure you understand the
- difference-- so T cells.
- They both have T cell receptors, but the helper T
- cells bond to MHC II complexes.
- Let's say that this is a helper T cell right here.
- It would want to-- not all helper T cells will.
- Only the ones that have the right combination, the right
- variable portion right here that just perfectly bonds to
- this combination of an antigen and the MHC II complex-- this
- type of helper T cell will bond here, get activated, and
- start differentiating.
- And the effector versions of them will start raising the
- alarms and the memory versions of them will stick around in
- case this type of thing needs to happen again.
- With MHC I, instead of attracting a helper T cell, it
- will attract a cytotoxic T cell.
- So like helper T cells, the T cell receptor has a
- non-variable portion, but it also has a variable portion
- that is specific to this combination of
- antigen and MHC II.
- So maybe this cytotoxic T cell will be involved when this
- cell goes cancerous.
- This cytotoxic T cell would be of no use-- or it won't bond
- to this one that was attracted to a virus.
- It's going to have to be another cytotoxic T
- cell that does that.
- And the mechanism where we get this variability in the helper
- T cells or the cytotoxic T cells or you saw in the B
- cells on their membrane bound antibodies, that all comes
- from when-- in their development stage or in the
- maturation process, the DNA that codes for these variable
- portions gets shuffled around intentionally.
- So normally, we're always trying to preserve DNA
- information, here it gets shuffled around.
- But anyway, once a cytotoxic T cell finds one of these guys
- on an MHC I-- remember, every nucleated cell in the body has
- an MHC I-- then what it does is, it gets activated.
- So let's say this guy says, hey, that looks shady.
- You need to die.
- So this guy gets activated and just like all other activated
- cells, he starts to divide and divide and divide and divide
- and differentiate.
- And he divides and he differentiates into memory,
- just in case you're going to need me again, just in case
- this type of cancer shows up again.
- And then also into effector T cells, which are the ones that
- do the killing.
- So this is an effector.
- So let's say one of these effectors-- they'll also bind
- to cancerous molecules, cancerous cells,
- just like this one.
- So let's say this cell has split and there's another
- version of it right here.
- That's what cancer does.
- It divides aggressively.
- It's producing wacky proteins.
- It presents the wacky proteins on its MCH-- major
- histocompatibility type I complex-- it displays the
- wacky proteins and then one of these effector cytotoxic T
- cells will be attracted to it just like that.
- And I'm not going into details on what necessarily does the
- attractions and all the membrane bound proteins.
- If you take an immunology class,
- you'll see more on that.
- So this is a cytotoxic T cell and it essentially forces this
- cell to kill itself in a couple of different ways.
- One, it actually can exocytose a bunch of proteins.
- They're call perforins-- that make little holes in the
- membrane of the cell.
- And it has other proteins that it releases called granzymes
- that go in here and essentially start mechanisms
- that make this cell want to kill itself.
- So the big picture is, if you want to just take 20,000 feet,
- these cells are very effective at produces-- so when a B cell
- gets activated, it produces antibodies that kill things
- that are floating around, right?
- Once a B cell gets activated, it starts producing a bunch of
- These antibodies float around and then they can bond up to
- viruses, make them ineffective, or essentially
- tag them for pickup from macrophages or dendritic
- cells, or other types of phagocytes-- while cytotoxic T
- cells-- these are used to essentially kill cells that
- have gone awry.
- For example, a cancer cell that's presenting weird
- proteins or once the virus has entered the cell, then the
- antibodies are really of no use.
- The antibodies aren't going to be able to
- get into those cells.
- In that case, instead of cleaning up the virus itself,
- a cytotoxic T cell will come here and just kill this cell
- because this cell is a virus factory.
- So you have to get it out of the way.
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