Health and medicine
- 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
- Inflammatory response
- Blood cell lineages
Learn about the role of B cells (B lymphocytes) in the humoral immune response. See how they are activated and produce antibodies that can recognize and bind to pathogens, leading to their destruction. The video also highlights the process of clonal selection and the importance of memory cells in immunity. Created by Sal Khan.
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- ok, I don't get why we still get a cold after we've already gotten it 4 dozen times. Shouldn't our body's have figured out what it is by then?(19 votes)
- Cold viruses are able to evolve through mutation and thus every time you get a cold it is probably a new version of the virus that your body has not encountered.(80 votes)
- I was taught that each antibody is specific for a single antigen (the lock and key model), but recently I have heard that scientists will mix serum from an individual with an unknown pathogen with a variety of known pathogenic viruses and bacteria. In this way, the antibodies to the unknown pathogen will react will one of the known pathogens that is closely related to the unknown one. This will give the scientists a clue as to the structure of the unknown pathogen. Is this correct?(10 votes)
- This is called a "cross-reaction" and is due to the fact that the related molecule looks partially like the original molecule. That is, they have structures in common. Maybe from the same virus family.(15 votes)
- are all of the possible varieties of the b-cell epitopes already present in the body before encountering the pathogen? For instance, in the video you say a b-cells will bump into this new kind of virus end eventually the b-cell with the correct epitope will attach, but does this mean it was already around the body, or did the b-cell dna segment devoted to epitope shape re-shuffle in the mean time?(12 votes)
- Excellent question. First: Antibody binding is not on-off; it can happen in a range of strengths.
Second: The body does indeed have a preexisting reservoir of randomly chosen epitopes.
Third: During an infection, the immune system is capable of searching for an epitope that will be more effective at binding the pathogen.
See http://en.wikipedia.org/wiki/Affinity_maturation and the pages it links to, such as http://en.wikipedia.org/wiki/Follicular_B_Helper_T_cells
T cells carry fragments of pathogens into the lymph nodes, where a B cell evolution factory is created. B cells that bind to the T cells (actually the antigen the T cells are carrying), even a little bit, are stimulated to divide with "somatic hypermutation" so you get a lot of varying copies. The ones that best match the T cells are stimulated to divide further; the others die.
After several cycles of this, you get B cells that make antibodies that bind quite well to the pathogen. Then they turn into memory and effector cells.
(Sal seems to be saying that the B cells dividing in the lymph nodes only create exact clones. I don't see how to reconcile that with the Wikipedia pages linked above.)(11 votes)
- Is it possible that a virus can avoid the immune system? If so, then what happens? Does it stay or does it get beaten by another antibody?(3 votes)
- The thing about viruses is that most of the time they do not float around on their own in your blood or your tissue. They insert themselves into your cells. Your immune system can only determine if a cell is infected by "examining" the proteins on the outside of your cells.
HIV and AIDS are two distinct things. HIV is the virus, AIDS is a condition that can develop in people who have the virus if left untreated.
One of the reasons the body has so much trouble with HIV is that the virus infects and kills your immune cells as part of its normal mode of operation. AIDS develops when your immune cell count becomes so low that you fall prey to normal everyday infections that your body typically would be able to fight off no problem.
One of the reasons there has been no vaccine for HIV yet is that the virus is capable of rapid evolution due to its short replication cycle compared to other viruses. There is a high amount of variability in the HIV genome so that a single strain can rapidly diversify into many strains, thus increasing the likelihood that the immune system will never be able to completely wipe out the virus from an infected host.
And as someone else answered, none of this happens as a result of any kind of conscious decision making. It is an example of evolution in action.(16 votes)
- In the video it is said that self-responding combinations are weeded out. How does that work?(5 votes)
- All cells have surface proteins generally called as antigens. Your own body cells also have surface proteins which makes them 'self antigens'. The B cells (and the T cells too as a matter of fact) are 'taught' while developing (in the bone marrow and Thymus respectively) to not react with the 'self antigens' (i.e. your own cells). The B and T cells undergo a selection process in the two organs and the B and T cells which react with the self cells are killed/ apoptosized.
This way the B (and T cells) which only recognise and attack the foreign (pathogen) cells survive. As mentioned by Ethan, this is called 'self immune tolerance'. Imagine if this weeding out was not happening, the immune cells (B and T cells) would start attacking one's own body cells too. This is what happens in most autoimmune disorders where the immune system can no longer differentiate b/w the 'self' and 'non self'.
Hope this helped :)(10 votes)
- This might be dumb, but where exactly in the body are the B cells encountering pathogens? I assume the lymph nodes, and then the specific antibodies they produce will travel through circulation to the site of injury or infection. Please help!(7 votes)
- Not a dumb question at all, lymph system collects some pathogens, APC's (antigen presenting cells) such as macrophages that have broken down a pathogen, and pathogen debris. These contents then travel to lymph nodes where B-cells and T-cells reside and become activated.(8 votes)
- What happens when a macrophage etc. eats a antibody with viruses, what happens to the antibody?(3 votes)
- what is an epitope? is it a shorter version of an antigen?(3 votes)
- Epitope is a specific target against which an individual antibody binds or you can call it an antigenic determinant.
B cell is recognizing epitope, internalizing pathogen and then presenting on APC.
In short, it is not antigen per se but, part of an antigen.(4 votes)
- I am confused about what the memory B cell ends up doing. I understand that it lasts a long time and each memory cell has (did he say 10,000?) antibodies on its membrane... but what actually happens when a memory B cell encounters another pathogen/antigen? Does it wait to get activated by a helper T cell and then undergo mitosis + differentiation? Is that all it does? Does it do this any differently than a virgin B cell would (i.e. is it more effective at this, does it have more antibody receptors than a virgin B cell, etc.?)?
If the activated memory B cell does differentiate, what does it differentiate into? More memory B cells and plasma/effector cells? Is this differentiation process any different than that of a virgin B cell that gets activated?(3 votes)
- A memory cell, including a helper T cell, undergoes mitosis more quickly, and activates other memory cells more quickly. These are clones, there is no further differentiation, these cells are specific to that specific antigen. Example, a person is infected with measles. The virus replicates, activates the specific immune system, and creates memory cells. During this time the person has a rash and fever etc.all the symptoms of measles. The next year they are again infected with measles but they show no sign of it because their memory cells destroy it. The b cells produce millions of antibodies that immediately attach to free viral particles in the blood and the t cytotoxic cells destroy infected cells before millions of viral particles are made inside the cell.The point is once activated, memory cells are forever vigilant.(3 votes)
- It is said no one has immunity to the coronavirus. Does that mean our B-cells do not have the proper combination of the variable on the protein that would match the coronavirus? After someone recovers from the virus they would now have the memory cells? How could they if they didn't have the proper B-cells to start with?(2 votes)
- You missed this important information: our B-cells need to be activated by the virus first. Many people recover and they do have antibodies as well as memory cells. After someone recovers from a virus, they have memory cells that protect them from the same virus. We expect that this virus will create that same future immunity, although it is new to us and too soon to tell how long that immunity will last. This is the point of vaccination, to use a weakened virus or parts of a virus to activate the acquired immune system. The vaccine will cause it to activate B cells that create antibodies and activated T cytotoxic cells as well as memory cells. Then when the real virus enters the body that has been vaccinated, it will be 're-activating' the acquired immune system. In short, our B cells have to interact with the virus, the 'proper ones' are there, but they are not active. Think about the 'common cold', you have 5-7 days of feeling stuffy, sore throat, etc. and then you 'get over it'. What happened? In that 5-7 days, the proper B cells activated and worked to destroy the virus. Yes you were sick, and then you got better. Thanks immune system. The problem with this Corona virus and Ebola is that it kills a higher percentage of people than the common cold.(4 votes)
Let's just talk about the humoral response right now, that deals with B lymphocytes. So B lymphocytes or B cells-- let me do them in blue. So let's say that that is a B lymphocyte. It's a subset of white blood cells called lymphocytes. It comes from the bone marrow and that's where the-- well, the B comes from bursa of Fabricius, but we don't want to go into detail there. But they have all of these proteins on their surface. Actually, close to 10,000 of them. I get very excited about B cells and I'll tell you why in a second. It has all of these proteins on them that look something like this. I'll just draw a couple of them. These are actually protein complexes, you can kind of view them. They actually have four separate proteins on them and we can call these proteins membrane bound antibodies. And I'll talk a lot more about antibodies. You've probably heard the word. You have antibodies for such and such flu, or such and such virus, and we're going to talk more about that in the future, but antibodies are just proteins. They're often referred to as immunoglobulins. These are essentially equivalent words. Antibodies or immunoglobulins-- and they're really just proteins. Now, B cells have these on the surface of their membranes. These are membrane bound. Usually when people talk about antibodies, they're talking about free antibodies that are going to just be floating around like that. And I'm going to go into more detail on how those are produced. Now what's really, really, really, really, really interesting about these membrane bound antibodies and these B cells in particular is that a B cell has one type of membrane bound antibody on it . It's going to also have antibodies, but those antibodies are going to be different. So we'll focus on where they're different. Let me just draw them the same color first and then we'll focus on where they're different. These are both B cells. They both have these antibodies on them. The interesting thing is that from one B cell to another B cell, they have a variable part on this antibody that could take on a bunch of different forms. So this one might look like that and that. So these long-- I'll go into more detail on that. The fixed portion, you can imagine is green for any kind of antibody, and then there's a variable portion. So maybe this guy's variable portion is-- I'll do it in pink. And every one of the antibodies bound to his membrane are going to have that same variable portion. This different B cell is going to have different variable portions. So I'll do that in a different color. Maybe I'll do it in magenta. So his variable portions are going to be different. Now he has 10,000 of these on a surface and every one of these have the same variable portions, but they're all different from the variable portions on this B cell. There's actually 10 billion different combinations of variable portions. So the first question-- and I haven't even told you what the variable portions are good for-- is, how do that many different combinations arise? Obviously these proteins-- or maybe not so obviously-- all these proteins that are part of most cells are produced by the genes of that cell. So if I draw-- this is the nucleus. It's got DNA inside the nucleus. This guy has a nucleus. It's got DNA inside the nucleus. If these guys are both B cells and they're both coming from the same germ line, they're coming from the same, I guess, ancestry of cells, shouldn't they have the same DNA? If they do have the same DNA, why are the proteins that they're constructing different? How do they change? And this is why I find B cells-- and you'll see this is also true of T cells-- to be fascinating is, in their development, in their hematopoiesis-- that's just the development of these lymphocytes. At one stage in their development, there's just a lot of shuffling of the portion of their DNA that codes for here, for these parts of the protein. There's just a lot of shuffling that occurs. Most of when we talk about DNA, we really want to preserve the information, not have a lot of shuffling. But when these lymphocytes, when these B cells are maturing, at one stage of their maturation or their development, there's intentional reshuffling of the DNA that codes for this part and this part. And that's what leads to all of the diversity in the variable portions on these membrane bound immunoglobulins. And we're about to find out why there's that diversity. So there's tons of stuff that can infect your body. Viruses are are mutating and evolving and so are bacteria. You don't know what's going to enter your body. So what the immune system has done through B cells-- and we'll also see it through T cells-- it says, hey, let me just make a bunch of combinations of these things that can essentially bind to whatever I get to. So let's say that there's just some new virus that shows up, right? The world has never seen this virus before this B cell, it'll bump into this virus and this virus won't attach. Another B cell will bump into this virus and it won't attach. And maybe several thousands of B cells will bump into this virus and it won't attach, but since I have so many B cells having so many different combinations of these variable portions on these receptors, eventually one of these B cells is going to bond. Maybe it's this one. He's going to bond to part of the surface of this virus. It could also be to part of a surface of a new bacteria, or part of a surface for some foreign protein. And part of the surface that it binds on the bacteria-- so maybe it binds on that part of the bacteria-- this is called an epitope. So once this guy binds to some foreign pathogen-- and remember, the other B cells won't-- only the particular one that had the particular combination, one of the 10 to the 10th. And actually, there aren't 10 to the 10th combinations. During their development, they weed out all of the combinations that would bind to things that are essentially you, that there shouldn't be an immune response to. So we could say self-responding combinations weeded out. So there actually aren't 10 to the 10th, 10 billion combinations of these-- something smaller than that. You have to take out all the combinations that would have bound to your own cells, but there's still a super huge number of combinations that are very likely to bond, at least to some part of some pathogen of some virus or some bacteria. And as soon as one of these B cells binds, it says, hey guys, I'm the lucky guy who happens to fit exactly this brand new pathogen. He becomes activated after binding to the new pathogen. And I'm going to go into more detail in the future. In order to really become activated, you normally need help from helper T cells, but I don't want to confuse you in the video. So in this case, I'm going to assume that activation can only occur-- or that it just needs to respond, it just needs to essentially be triggered by binding with the pathogen. In most cases, you actually need the helper T cells as well. And we'll discuss why that's important. It's kind of a fail safe mechanism for your immune system. But once this guy gets activated, he's going to start cloning himself. He's going to say, look, I'm the guy that can match this virus here-- and so he's going to start cloning himself. He's going to start dividing and repeating himself. So there's just going to be multiple versions of this guy. So they all start to replicate and they also differentiate-- differentiate means they start taking particular roles. So there's two forms of differentiation. So many, many, many hundreds or thousands of these are going to be produced. And then some are going to become memory cells, which are essentially just B cells that stick around a long time with the perfect receptor on them, with the perfect variable portion of their receptor on them. So some will be memory cells and they're going to be in higher quantities than they were originally. So if if this guy invades our bodies 10 years in the future, they're going to have more of these guys around that are more likely to bump into them and start and get activated and then some of them are going to turn into effector cells. And effector cells are generally cells that actually do something. What the effector cells do is, they turn into antibody-- they turn into these effector B cells-- or sometimes they're called plasma cells. They're going to turn into antibody factories. And the antibodies they're going to produce are exactly this combination, the date that they originally had being membrane bound. So they're just going to start producing these antibodies that we talk about with the exact-- they're going to start spitting out these antibodies. They're going to start spitting out tons and tons of these proteins that are uniquely able to bind to the new pathogen, this new thing in question. So an activated effector cell will actually produce 2,000 antibodies a second. So you can imagine, if you have a lot of these, you're going to have all of a sudden a lot of antibodies floating around in your body and going into the body tissues. And the value of that and why this is the humoral system is, all of a sudden, you have all of these viruses that are infecting your system, but now you're producing all of these antibodies. The effector cells are these factories and so these specific antibodies will start bonding. So let me draw it like this. The specific antibodies will start bonding to these viruses and that has a couple of values to it. One is, it essentially tags them for pick up. Now phagocytosis-- this is called opsonization. When you tag molecules for pickup and you make them easier for phagocytes to eat them up, this is what-- antibodies are attaching and say, hey phagocytes, this is going to make it easier. You should pick up these guys in particular. It also might make these viruses hard to function. I have this big thing hanging off the side of it. It might be harder for them to infiltrate cells and the other thing is, on each of these antibodies you have two identical heavy chains and then two identical light chains. And then they have a very specific variable portion on each one and each of these branches can bond to the epitope on a virus. So you can imagine, what happens if this guy bonds to one epitope and this guy bonds to another virus? Then all of a sudden, these viruses are kind of glued together and that's even more efficient. They're not going to be able to do what they normally do. They're not going to be able to enter cell membranes and they're perfectly tagged. They've been opsonized so that phagocytes can come and eat them up. So we'll talk more about B cells in the future, but I just find it fascinating that there are that many combinations and they have enough combinations to really recognize almost anything that can exist in the fluids of our body, but we haven't solved all of the problems yet. We haven't solved the problem of what happens when things actually infiltrate cells or we have cancer cells? How do we kill cells that have clearly gone astray?