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Health and medicine
Course: Health and medicine > Unit 1
Lesson 9: Immunologic system introduction- 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
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Clonal selection
Clonal selection is a process by which the body produces B and T cells to respond to infections. These cells each have unique receptors that allow them to identify specific pathogens. When the body encounters an infection, the B and T cells that can recognize the invader multiply rapidly to create an army of cells to fight it. Created by Patrick van Nieuwenhuizen.
Want to join the conversation?
- When lymph nodes become inflamed and swollen due to our body fighting off some type of infection, is that due to the rapid proliferation of the B and T cells or an innate inflammation response? Or perhaps both?(31 votes)
- As far as i know, swollen lymph nodes are both because of increased proliferation of the B and T cells as well as an increased migration of antigen presenting cells to the lymph nodes. Swollen lymph nodes can also be a sign of cancer, and in that case the reason for the swelling is because of metastasis (the cancer spreading) via the lymph.(24 votes)
- Do T cells originate in the bone marrow and then migrate to the thymus to mature? Or do they just go through their entire creative process in the thymus?(14 votes)
- Both B and T cells originate in the Bone Marrow, but T cells leave and mature in the Thymus while B cells mature within the Bone marrow.(37 votes)
- So, the B cells sees a pathogen, lets call the pathogen Mr. Potato Head.
1) Does Mr. Potato Head have multiple epitopes that can present to different B (and T) cells? (His hands have an affinity for a 'red B' and his legs have an affinity for a 'blue B'.) The cascade of events would then depend on which epitope was presented to the correct B cell first or which had the better fit.
2) Can two 'red' B cells attach to one Mr. PHead at the same time? One 'red' B cell to each hand?
3) Can two Mr. PHeads attach to one red B cell at the same time?
3) Once a (let's say purple) B cell absorbs Mr. Potato Head do the MHCII complexes present all or most of his body parts outside of it's cell (so we have a ball presenting the arms, legs and other various body parts) or is it just ONE portion of Mr. PHead that is presented (a ball presenting hands to the outside world). - I vote for the first option there, but I dont know.
s say it is indeed the first option and we have a purple B cell presenting the various parts of Mr. PHead to the outside world. A purple Tcell comes along. Are its purple receptors specific to the hands or can they recognize any of Mr PHead`s body parts presented by the MHCII complexes of the B cell? If it can recognize any of the arms, legs or eyes of Mr. Potato Head then there is a great deal of variability that the purple T can recognize. How does it know this is the pathogen it was created to destroy?
4) Let
5) It is amazing that any of this can actually work!! In fact, it's barely believable when you think about it. Even IF we have the same rainbow of B (and T) cells present in every node of the body there are billions of chances that a pathogen WON'T come into contact with the correct B/T cell. Does the pathogen spend a long time in the nodes? How does our body increase our chances of contact?
Wow.(13 votes) - I realize that B (and T) cells come in billions of 'colors'. Are there billions of 'red' B (and T) cells and so one 'red B' would reside in each node of the body? (ie. Therefore each node has the same 'rainbow' of B and T cells?) or
is there only one 'red' B (and T) cell in the entire body? ....it can`t be this second option, but how does the first option work?(7 votes)- Each node doesn't present the same rainbow precisely; however, they do have a wide array of B cells within each node, and in fact, more and more "colors" are being generated all throughout your lifetime, provided you have functional hematopoetic stem cells. Because the lymphatic system is circulatory and B cells mediate humoral immunity, if the appropriate antibody isn't generated for a given antigen in one lymph node, it will (hopefully) be caught in the next lymph node in the chain.(6 votes)
- Why can't T cells recognize a pathogen directly? It seems counterintutitive that it can recognize a broken piece on MHCII but not the whole bacterium?(5 votes)
- The fact that T cells need MHC II proteins to be activated acts as a "double handshake" to make sure proliferation is necessary. If T cells could recognize a pathogen directly it may cause unnecessary energy to be used for cell division. This is why multiple immune interactions need to be made in order to activate an adaptive response.(10 votes)
- Do Lin B need the Lin T helper to get activdated, or they can just start cloning themselves by just attatching the bacteria?
Thank you for your help. This website is incredible!(5 votes) - AtIt was mentioned that the B and the T cells are going to replicate .Where does this replication take place ? Is it in the lymph nodes? 8:00(4 votes)
- mostly, yes, but that's not to say they wouldn't replicate if there were to come across the relevant pathogen outside of the lymph node.(3 votes)
- Where do all the different kinds of cells come from?(3 votes)
- hematopoitic stem cells (which differentiate into leukocytes, white blood cells, and erythrocytes, red blood cells) are located in the bone marrow(5 votes)
- What allows the cells to create identical clones of themselves as they weren't making clones before they found the pathogen?(3 votes)
- So, if a B-Cell "daughter" and T-Cell "daughter" are in the lymph node and are not activated by an antigen, would the replicate into more "daughters" or would they die normally?(2 votes)
- Is there additional work or research available regarding mutations in the cells during production such that they have more than one type of receptor on the same cell membrane or perhaps gene therapies that can produce the same effect?
As it is, the original process only yields a cell with a specific receptor. The body must shuffle the genes in the first production phase (before activation) to produce another cell with a different type of receptor. My question is in regards to this phase.(3 votes)
Video transcript
In this video, I'd like
to give an overview of how the B and T cells in your body are prepared to fight infections. And so, let's start with
where B cells come from. So where do B cells come from? They come from the bone marrow. So, here's a bone and
inside it we have some bone marrow, and it's from
there that B cells come from. But the process by which the B cells are prepared in the bone marrow is actually very interesting and unique
in terms of the human body. Because well, like many
other places in the body, the B cells divide and form millions of descendants and that
is how your whole body grows and comes to be as big as it is. But, for B cells there's something very different from other parts of your body, and that is that each daughter cell that grows up in the bone
marrow is different from its parent and is also different
from all of its siblings. So, just to remind you, B cells have these receptors that later on
will be their antibodies. But each daughter cell of this original B cell will have a different receptor. And that's because, in
the process of being made, these daughter B cells will have a slight shuffling, a slight changing in their DNA, but specifically for this receptor, and so by the time they're created, they have a unique receptor that
will identify a unique criminal, a unique bacterium or virus or something in the body. That receptor will be useless for all the other criminals in the body. So, it's very specific but very powerful if it finds the thing
that it wants to kill. So, this is happening in the bone marrow. And, basically the same exact thing is happening for T cells, except it's not happening in the bone marrow,
that's happening here. You know what this is called? This is called the thymus and I'm drawing it a little bit
bigger than I should, maybe, but that way
you can see it clearly. The thymus has two lobes or two parts, and it's located right
behind your sternum. So, T cells come from the thymus. And, very similar to B cells,
they have a unique receptor. It's not quite the same and it doesn't become an antibody later on. They have a unique receptor and, while these T cells are dividing and creating millions of daughter T cells, each of these daughter T cells will have its own unique receptor that will also identify a unique criminal or
bacterium in the human body. And we remember that these receptors actually find antigens, so pieces of these criminals that are presented to them by antigen presenting cells and
we'll revisit that in a second. So, all this is occurring in the thymus. And so, this is step
one of the process and it's unique to the human body because we end up with all these actually, literally genetically different
B and T cells that are very specific to things
which may or may not even exist out there because they're
really created at random. Now, the next thing that happens is that these B cells and T
cells, once they're ready, are going to migrate to a lymph node, and you have lymph nodes all over
your body, about 600 of them. But, let's say that they go
to one here, in your armpit. They're going to migrate
to that lymph node, for example, and that is where they're going to wait for their special criminal that they can react to. So, they're going to go over
there to that lymph node. And let's draw that down here,
maybe significantly bigger. So here's the lymph node, and you're going to have your B and T cells, all the different kinds of them,
lying in wait there. And they have their special receptors. Each one is specific to something else. So, these guys have migrated here to all the different lymph nodes of the body. And now these guys are ready, and so the next step is really infection, so let's look at a tissue in your
body with some cells. These are cells, let's
say it's over there. So it's not too far from
that lymph node there. And let's say it gets infected. So here are some bacteria
which are causing damage. And one of the things we have out here is these cells, which are
part of the immune system, which are called dendritic
cells, dendritic cells. And these cells can eat some of these bacteria, so they can
actually kill some of those bacteria, they can ingest them. But, it's actually not quite to the point that they can defeat this infection and that's not really their purpose. And their purpose is
actually more to present these bacteria to the B and T cells that we've been talking about. And so, the way that they do that is that they come here into
these lymphatic vessels, which start here in the tissue, and they go up to the lymph node where they're going to present these
bacteria to these cells. And at the same time,
some of the bacteria might also get swept in there and
might go into the lymph node. And so, you get some of them out here. You get some bacteria and maybe just some pieces of bacteria that got broken down. And you also have your
dendritic cells here, which are antigen presenting cells, which means that they have this protein that we've talked about
called MHC, MHC, on which they present pieces of those
bacteria that they've ingested. Now these T cells here
are unable to identify these bacteria when they're
just freely floating. They need this antigen presenting cell to show this piece of bacteria to them. And only the T cells, which can recognise this very specific pathogen, are going to see it and bind to it and react to it. So in this case, it's this guy. He's going to bind to
that little piece and recognize that his invader, the one guy he's been created to kill
is somewhere in the body. Meanwhile, these B cells are made to react directly to these bacteria without this antigen presenting cell. And so, the specific one that is specific to this bacterium is going to see it, bind to it and also be alerted. However, all these other guys? They're not going to know
that anything's going on. Because, they can't bind to any of these pathogens that were brought
into the lymph node. And so, this right here is step two. When the infection occurs, and the right B and T cells are alerted. And what are they going to do now? Well now, they're going to activate. They're going to jump into action because finally they're needed. Now these B and T cells are going to start replicating like crazy. So here are the two lucky
winners who got selected. And they're going to say, "well, "now that we know we
are useful for fighting "this infection, we better
replicate like crazy "because right now there's only two of us "and that's not nearly enough." So, they're going to start replicating, and each of their descendants, unlike this kind of replication, now each of their descendants is going to have the same receptor. It's going to have the same receptor. If it had a different receptor, this whole process would be useless
because it wouldn't be able to fight the specific infection
that we've just identified. And I should mention that not all of these guys are going to do the same thing. So, most of them will
become effector cells, which means that they're going to be ready to fight this infection right now. But some of them are going to become memory cells, which means that they're not going to actually fight right now. They're going to wait until the next time that this pathogen comes around. And the reason why we create these guys is because if we get this bacteria once, there's a high chance that
we're going to get it again. Because, really, you create billions and billions of these different receptors, but only a very small subset of them will actually end up being
pathogens that you see. And so, this is step 3 of our process, which has finally resulted in an army of B and T cells, ready to
fight this specific invader. So that's what they're going to do now. The B cells are going
to pump out antibodies to attack this bacterium and the T cells, some of them are going
to stay in the lymph node and some of them are going to travel out to this site to join the battle. And so, this whole process can actually be called clonal selection,
clonal selection. Which is a name for the theory of this process when it first came out. So this is clonal selection and the reason it's called clonal selection is because you're going to select B and T cells that you need and then you're going to start cloning them like crazy into this army. And the process involves all these very unique, specific B and T cells coming from the bone marrow and
thymus to the lymph node, where they're going to be met by these bacteria that are infecting your skin, that are going to travel through the lymphatic vessels to the lymph node. And so, they'll meet there and then the armies will be prepared.