- Immune system questions
- Innate immunity
- Adaptive immunity
- Role of phagocytes in innate or nonspecific immunity
- Types of immune responses: Innate and adaptive, humoral vs. cell-mediated
- B lymphocytes (B cells)
- Professional antigen presenting cells (APC) and MHC II complexes
- Helper T cells
- Cytotoxic T cells
- Review of B cells, CD4+ T cells and CD8+ T cells
- Clonal selection
- Self vs. non-self immunity
- How white blood cells move around
- Blood cell lineages
Cytotoxic T cells
How cytotoxic T cells get activated by MHC-I/antigen complexes and then proceed to kill infected cells. Created by Sal Khan.
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- Hello, thank you so much for all the brilliant videos you post !
My question is about B cell showing a MHC1 compatible with a Tc cell.
When a B cell recognize a pathogen, it put one bit at the to of its MHC2 complex and then the Th cell recognize it and activate the B cell so it can create plenty of antibodies that will help the body to destroy the pathogen.. I am rigth?
But then... if the B cell shows at the same time, a MCH1 with a little bit of the pathogen on it.. a Tc cell will recognize it and will destroy the B cell, won't he?? That means that the B cell will not be able to produce antibodies anymore! Isn't that illogical for our safety?
Thank you so much for helping me understand such a tough subject =) !(9 votes)
- That's a very good question.
The answer is that additional proteins on the surface of T cells act as co-receptors and allow cells to distinguish between MHC class I and MHC class II complexes.
On cytotoxic T cells, there is a protein called CD8 which binds MHC class I complexes and so means these cells will not bind B-cells presenting antigens on MHC class II complexes, only infected cells presenting antigens on MHC class I.
On helper T cells is a protein called CD4 which binds MHC class II complexes, so allows them to bind B-cells presenting antigens and activate them, but they will not bind infected cells presenting antigens.(13 votes)
- Hello Sal, I have a question about the cancer cells. You said that cytotoxic T cells can make a cancer cell destroy itself... well then how does cancer manages to beat our immune system?(7 votes)
- It can, but it doesn't do this in 100% of cases. Our immune system is not ideal, it can fail to track cancer antigen, tumor cells may still appear to be normal. Their outer appearance (proteins and other molecules on their surface) may look unchanged, even though profound changes may be happening on the inside. In this way, these abnormal cells manage to escape attack by the immune system and grow and multiply without triggering an immune response. This is how it's possible for a tumor to form, even when your immune system is working normally.
When it detects cancer cells and attacks them, the attack may succeed, or it may come too late: the tumor may be beyond the power of the immune system by itself.(12 votes)
- thankyou so much for the wonderful explanation
the question i have is: if even b cells have MHC 1, why don't they attract the cytotoxic T cells??(6 votes)
- Cytotoxic T cells are very specific. There is a different one for each antigen. A cytotoxic T cell will bind only to cells with an MHC 1 that is presenting the specific antigen that the cytotoxic T cell is supposed to bind to. So if a B-cell's MHC 1 is presenting the right antigen then the cytotoxic T cell will bind and kill it. This would only usually happen if the B-cell is infected.(7 votes)
- If our immune system kills infected cells and pathogens in fluids, how do sicknesses worsen and end occasionally in death? Is this an effect of the immune system not working fast enough?(5 votes)
- It depends on the sickness. The immune system isn't perfect. In some cases, it simply isn't powerful enough to hold off the disease, like a tower defense game on the last level. Other times, your own body kills you. For example, fevers are a natural defense. They allow your immune system to work more effectively. However, they occasionally get out of hand and can potentially result in death.(4 votes)
- i wonder that if redblood cell doesn't have MHCI, so how are they avoid being kill by NK cell?(3 votes)
- To clarify, NK cells and cytotoxic T cells are tightly regulated and both have activation receptors and inhibitory receptors, and require signals from BOTH to actually determine whether or not to kill a cell.
So while red blood cells lack an MHC 1 molecule to inhibit NK cells, it also lacks the ligands and signals required to actually activate them, and thus a healthy erythrocyte will not be targeted by NK/CD8 cells. There are other factors as well, with RBCs having their own self-marker but hopefully this helps.(6 votes)
- When a cytotoxic T cell eliminates the infected cell, does the pathogen die in that process or does it just come out of the cell and exist in the interstitial fluid?(4 votes)
- It exists in the interstitial fluid. So that as it waits B-cells come by and tag it for destruction.(2 votes)
- why self proteins of infected cell are not recognized by cytotoxic T cells?(2 votes)
- I think I mentioned that you won't go into it, but I'd be interested in knowing more about how the T Cells are "attracted" to the MHC I and II complexes. Is it that they are constantly looking at all the cells, something signals them to start looking, or there is something attracting that specific version of the T Cell.(2 votes)
- DNA within each T-Cell tells it what MHC complexes to recognize based on what genes are turned on in that cell. Also, chemical signals between each cell is what mediates the responses and recognition. At least that is what I believe happens :D(3 votes)
- Corneocytes loose their nucleuses, but do they retain their MHC1s?(2 votes)
- Corneocytes are dead cells. Therefore they cannot act as antigen presenting cells. The function of MHC I is to present endogenous antigens(viruses, tumor) to Cytotoxic T Lymphocytes. Since they are dead cells I don't think there is any importance in the fact if they do, or do not retain MHC Class I.(3 votes)
- Just a quick question for all the T cells such as the Helper T Cell and the Cytotoxic T Cell. When they bind to either MHC I or II such as a Helper T Cell binding to a Pathogen on a MHC II then dividing when activated does the Effector cell also shuffle its genes but it still has the same combination as the precursor T helper Cell? same with Cytotoxic T cells when they bind to MHC I?.. also another question. Are B Effector Cells the only cells which are named plasma cells? or are T effector Cells called Plasma Cells too?
So from which Ive studied so far. B Lymphocyte cells have over 10 billion combinations on there variable portions to bind to a certain Pathogen? does the same go for T cells with there Combinations?
Sorry if my question might be far fetched just trying to follow up from B Lymphocyte Cells to Here on Cytotoxic T Cells.(2 votes)
- The recombination occurs before binding occurs, as they form the unique receptors by which the t-cells are able to attach to either MHC I or II cells.
Remember that CD4 or T Helper cells bind to MHC II, while CD8 or Cytotoxic T cells attach to MHC I. A quick way to remember this if we use multiplication to assume that each has to equal to 8.
ex. CD4/MHC II = 4(2) = 8.
To my understanding, another term for effector T/B cells is plasma T/B cells.
Each variable region on the tips of the antibody has only one combination. In either T/B cells, each receptor is therefore unique from another receptor.(2 votes)
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 antigens and MHC I. 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 antibodies. 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.