Video 1: Maturation of T-Cells
So welcome to the immunologic course and a lecture on adaptive immunity. So, uh, in our last lecture, we started describing about the. In it immune system, which we described as the very first response of our body against any pathogen or any, uh, external invasions. So the immune risk, the inept system, as I described is the first line of defence. And then when the, in it system, Is unable to respond or unable to contain that, uh, infection or, uh, uh, that infection. Then it tries to transfer the message to the adaptive system. Now, who is the eruptive system and how does that Aaptiv system work? So we will try to get an overview of how. The in it system and the adaptive system works together in how this message from the Nett system is being processed by the adaptive system and the cells of the adaptive immune system. They start to work now who are the sales of the adaptive immune system, primarily duh lymphocytes. The T N the billing for sites. So again, the additive immune system can also be divided into that cell-mediated part and the humeral part. So the cell-mediated part is mainly mediated by the T-cells and the T-cells again are of the T helper type and the cytotoxic T-cells. We know that. And we have the B cells, which is the humoral part of the immunity. There is a humoral immunity that is antibody mediated. So this is the very broad classifications. Now we have to look how the cells of the innate system. They bring the, or carries the message from the unit system to the eruptive system and how that activates that up to system or the sales of that. Our two systems are getting activated. So of course, uh, uh, let us start again from the beginning where we have seen that dialysis at the cells of disruptive system, like the antigen presenting cell. Now these antigen presenting cells are the main connectors between the two systems who are the antigen presenting cells. The antigen presenting cells are mostly the macrophages or. The dendritic cells, these cells, they engulf the pathogen. So grossly, the idea is like this, that this cells, they engulf the pathogen and then they process it and chops the protein components into small PIP types. And the present it on the surface by two classes of MHC molecules. Either class one or the class two. Now it depends on what type of antigen it is presenting, depending on that it uses class one or the class two images to present the antigen. So now this cells of the innate system expressing MHC class one or class two, carrying the antigen will enter the adaptive system and we'll activate. The cells of the adaptive system, as I told the sales of that uplift system are the T-cells and the B-cells. So in this lecture, we try to summarize or try to see how it activates the T cells. So if you look into the picture here, it is the bone marrow, which is the site of. Starting point. So all the cells of the immune system are coming from there. So that T cells, the B cells, they, or their progenitors. So for example, they are called the lymphoid precursors. So now this lymphoid precursors, they enter from the live, the bone marrow and they enter into the bloodstream and they migrate. So we have discussed a little bit about, uh, migration of the cells, uh, in our, uh, class of, uh, in our lecture, on the inflammation, mostly the migration or the extravasation of the neutrophils, similarly, this, uh, other lymphocytes or leukocytes other, uh, lymphocytes. They also migrate. And these T-cells or the T-cell precursors, we call them the T-cell precursors because we don't call them the T-cells. They have not yet become mature T-cells so the first stage is their maturation, so they have to mature to get, become the T-cells. Now, what is a match? Your T-cells are match. Your T cell should have, should have what we call our T cell receptor. So it should be expressing a T-cell receptor. And along with it, our core receptor, which is, which can be a CD eight or a CD four core receptor, this are required for recognition and binding to the MHC molecules. So these match, your diesel has to be first produced, and this is produced in the timeless. This maturation process starts in the timers. So this precursor cells. The T cell precursor, we now call them the T cell precursor.
So now this T cell precursors, they enter into the Pimas and inside the timers, the timers you can, if you see have a magnified view of this, then you will see there is a Cortex region and cortex region. So this maturation privately occurs in the cortex region. What happens here? This precursor cells, when they enter into the timers, they neither express any of the CD four or the CD eight. Nor the express that T-cell receptors. So they are not yet dessert T-cells or match your T-cells. So they, these cells, they start to get Matchu inside the timers. And since they are not expressing either of the two core receptors, like the CD four or the CD eight, that means this cells are CD four minus. CD eight minus. So the CD four and the CD eight are the markers of these T-cells. So we call them the markers to identify what kind of T-cells they are, or finally to what kind of T-cells they will differentiate into. So CD four and the CD eight minus diesels are also called the double negative. Because they are negative to both the CD four and eight. So they are also called the double negative cells. The next stage, once they enter the timers, the next stage is they will start to get matched your, and they will pass through several double negative stages. So we call them like double negative one double negative two. That means the cells are still not expressing the CD four or the CD eight core receptors on the surface. And in the meantime, what happens is there is rearrangement of that T-cell receptor. So there is this. You will be starting about T-cell receptors and T-cell receptor year and remains in details later on. But for the time being, uh, just for your understanding. So there is a T-cell receptor rearrangement during this double negative stage. So it rearranges and at the stage. When the cells are still double negative, that is den for at this stage, they start to express the diesel receptors. Now they are expressing the T-cell receptors, but they are still not expressing the core receptors. So that means they are still double negative. They are CDA negative CD, four negative. Now, these cells start to express on their surface, both the CD four and the CD eight. So, and of course that T-cell receptor. So this is the TCR and they are C, D four plus. As well as CD, sorry, as well as they are CD eight plus. So now this stage is known as double positive stage. So that means they are not any more double negative. They have started expressing on their surface, the T-cell receptor. As well as both the CD four and the CD eight core receptors, which means although they are expressing the core receptors, but they are still not designed. They are still not designed to bind a specific class of MHC molecules. Now they have to be selected for that. Now, who is doing this selection. Someone has to select these double positive cells and finally end up in either city four plus cells or the CDA plus cells. So who is doing that? So inside the timers, we have the timing epithelial cells. So there's time, Mick IPI hellion cells. They express. The different MHC molecules, the class one and the class two molecules on their surface. Now this time it gave cells, they are kind of helping this T-cells to match you and select one of the C either, either selected as a city four plus. Or selected as a CD eight plus cells. So these cells, as I told they are expressing the MEC's on their surface, this timing, epithelial cells, they are expressing on their surface. They may seize. So depending on the type of MEC molecule it is interacting with. So if this double positive cell. Is interacting with an MHC class one, then it is going to become a CD is going to become a city, a plus cell C D a plus cell expressing the CD eight coreceptor only if. It is interacting with the class two MEC by the CD four coreceptor. Then it is going to be a CD four plus cell. Now what happens to those cells, which do not interact with timing, epithelial cells. So it's a process of selection. So that means there are also cells which might not interact with those timing epithelial cells. So those cells, which are not. So these are the cells which are interacting those cells, which do not interact with the timing epithelial cells. They are not selected and they will die by apoptosis. So these cells will then die by apoptosis.
Video 2: Activation of T-Cells
Now, these cells, which has been selected as CD eight or CD four plus cells, these are still the naive T cells. So they are the knife cells because they have not yet encountered with any foreign antigens. So those, so there's, they have not been activated. So now these cells, they still have not encountered with any foreign antigen. So that is why we call them as the naive cells. So these are the knife T cells. Now these knife cells, after being selected as the CDA plus, and the Citi four plus cells, they can undergo a second round of, uh, selection. And this selection occurs usually by the help of the macrophages or the antigen presenting cells. So they can undergo a second round of selection and those which are selected as CD four or CD eight plus cells, we know there will no leave the timers and. They will not leave the timers. So these are the knife T-cells expressing either CDA or CD four. So they are the knife cells expressing either CD eight or the CD four. They will now go to get activated. Where do they go for activation? So now they will migrate to. Specialized organs like the lymph node, for example. So let us see how, what happens in this lymph node. So, so this is kind of a picture. What we see in the lymph node and the lymph node is also having three major regions. One is the medulla, the batter cortex, and the cortex. So the middle arm. It's mostly filled up with T and B-cells match your B cells and the knife. This better cortex is a site for T-cell activation and the cortex is primarily the site for B-cell activation. So we will talk about, uh, this cortex area or the B-cell activation when we start either humoral immunity. So for the time being, let us concentrate on the bad aquatics. Where the T cell activation occurs. Now, this lymph node also apart from containing this T and the B cells or the T-cells and the B-cells in the cortex better cortex, they also contain the antigen presenting cells, like the dendritic cells and the macrophages, which are presenting the antigen on their surface by class one order plus two M it's similar. No, this, this diesel's as now, they are kind of disc time. So they have on their surface T-cell receptors as well as either CD four plus or the CD eight core receptors. So the CD four plus CD eight, plus decents. No for the activation of the T-cell, it has to meet the MHC molecule. The activation of the T-cell requires our MC meeting between the image, the molecules and the T-cell receptors and the core receptors. And this interaction is vital for activation of the T-cells and further differentiation into different T-cell types. So what happens here is inside the lymph node. Our T-cell interact with an antigen presenting cell, which can be a macrophage or even a Dendright XL, which is expressing the MHC molecules. It can be an MHC class one or MSC class two. Let us take an example of the music class too, from here. So let us say, this is the MHC class two, and this is a CD four, plus T-cell in this intro. This is the T-cell receptor and our city forward. Coreceptor apart from these interactions, the CD four plus or the CDA plus the T-cells, the knife T-cells they also express another marker on the surface, which is the CD 28. And this can interact with the B seven, the B seven. On the surface of the MSC on the surface of the macrophage order dendritic cells. That means antigen presenting cells. We call it in general as the APCs. So basically we see there are three different interactions operating. One is Dar DCR or the T-cell receptor. getting dark and pigeon. Of course. And, uh, coreceptor the CD four or the CD eight, depending on the type of disease, uh, uh, type of the T-cell. And along with that, uh, CD 28 to a B seven interaction, this interaction is particularly vital for the activation of. The activation off the teeth. So we call this the activation. So this, this part is the maturation and this bar is activation. So now the T-cell is activated after all these three interactions are complete. So it. Gets activated something similar happens with the CD eight plus cells as well. So the CDA plus cells will interact with antigen presenting cells, which are expressing MHC class one. So this is image C class one. And then this is the CD eight core receptor. The T-cell receptor, the DCR. And of course there is thus CD eight and B seven. CD 28 to be seven interaction. So this is a class one, it Mitzi. This is another antigen presenting cell, a PC. So this is a class one image interacting with the CD eight here. There's a CD eight and this is. CD four. So the cells which are expressing on their surface, the CD eight core receptors, they will finally form either the cytotoxic T-cells. Are the D memory cells. They will finally differentiate into the cytotoxic T cells or the team memory cells and this which interacts those, which interacts by the city for core receptors. With the MHC class, two molecules presented on the surface of the ABCs, then we'll finally produce different subsets of T-cells. So the T helper cells, so they can give rise to T H one D H two or. T H 17 or D H the direct cells are the regulatory cells, as well as a specific class of T-cells, which are also known as D FH or the follicular helper. T-cells are this TFH cells. And also the other T helper cells. They are required for helping in the activation of the B-cell. So they are also required in the humeral part of the immunity. So they will, uh, they are not really the effector T-cells. So the effector T-cells, if you see the effector T cells, which act to actually give the cell-mediated immunity or which actually performs a cell-mediated immunity are the th one and the th two cells. And the cytotoxic T-cells. So the cytotoxic T-cells are the class of T-cells, which directly can interact with the pathogen and can kill the pathogens. So they have that mechanism, they express certain effector molecules, which leads to after direct interaction with the pathogen that can lead to Destruction of the pathogen directly. So these are the effector cells. So either the class, the th one or the th two cells or the cytotoxic T-cells, and then you have the memory T cells. So this entire process occurs inside the lymph node, the pet aquatics of the lymph node and the T helper cells. Now these. These T-cells. So depending this depends on what type of cytokine is actually present in the surrounding. And depending on that, they start different differentiating into the different types of T-cells the th one or the th two or the or the TA or the TFH cells. So if we look into the whole picture, once again, Starting from, uh, here in the, in the bone model. So the T-cells and the B-cells, uh, the, the, the progenitor cells or the precursor cells, they enter into the timers, the T-cell precursors. They enter into the timers inside the timers, they get matched cured. So they initially these T-cell precursors, they match your, uh, through different stages. Where the T-cell receptor are rearranged the T-cell receptor rearrangement talkers. And during this time it does not express on its surface, either off the two markers, CD four or CD eight. And that's why they are known as the CD four minus CD eight miners or the double negative cells. This DN cells are the double negative T-cells. Then gradually start developing or expressing the T-cell receptors on their surface. They don't start to express these T-cell receptors on the surface and at the stage double negative four, they express the TCR or the T-cell receptors. And then they suddenly start expressing both the core receptor. That is the CD four and the CD eight. And they become CD four plus and CD eight plus. So now this CD four plus and CD eight plus T-cells are called the double positive cells. Now this double positive T-cells they have to be selected. Then now, who does this selection? It's that dynamic epithelial cells, primarily who can express class one and class two, we Mitzi's on their surface. And the select for the CD four plus or the CDA plus cells. So from the double positive cells, now they become single positive. So it's either a CD four plus or a CD eight plus. Now they are further subjected to another round of selection. By mostly the macrophages or the antigen presenting cells, which expresses the emit, sees on their surface. Plus one of the class, two images. And then finally the cells which are selected, they proceed to the lymph node for activation and those cells, which are not selected. That is, those are, those are not selected by the time he kept battalion cells, they get destroyed or they're killed by the process of apoptosis, programmed, cell death. And then this CD four plus, and the CD eight plus cells, the, which are still kind of naive T-cells they have not yet met with any. Antigen yet. So now they will go into the lymph node and they're there. They will encounter with the antigen presenting cells, which are presenting the antigens by class one or class two MHC molecules. So this is an interaction here showing the class two interaction or class two. We may see interaction with a city four plus cell and the class one emits the molecule, which interacts with the CD eight plus cells. So now, uh, the mid, the basic of the interaction is kind of similar. So it makes it class two interacts with the T cell receptor and the CD four coreceptor along with there is another co-stimulatory interactions. So this is called a co-stimulatory interaction between the CD 28 and the B seven. Which is expressed on the surface of the antigen presenting cells and the mature T diesels, they start expressing the city 28. So this city 28, two B seven interaction is also important for activation of the T-cells. Now these T-cells are now kind of activated and what also happens here. So these T-cells, they now start to express on their surface though. Receptors for cytokines, for example, I'll do R and the secret I'll do or interleukin two, and this in turn leads to their differentiation. So that, uh, class of, uh, interleukins, this helps these cells to differentiate into different types of effector cells or the memory cells. So either they will produce effector T cells. Which are the or the cytotoxic T-cells and they produce the memory T cells as well. So now, uh, this interaction between the CD four, uh, plus T-cells and the antigen presenting cells, having the class two Mac, that is which approved, uh, mostly, uh, exhibiting the up. Uh, bacterial or the exogenous, uh, uh, antigens presenting those antigens, they will be presented in these T-cells will get activated and they will now give rise to different subset of T-cells, which will be either effector T-cells or will produce the memory T cells. Similarly, the CD eight plus. T-cells they interact with class one, MHC molecules. So class one, MHC molecules are usually, uh, displaying viral antigens or, uh, self cell, uh, antigens. So this class one is molecules carrying that, um, antigenic peptide bound, bound class, one image, the molecules they interact with CD four plus diesels. And once this interaction is complete, along with this costimulatory interaction here shown for the city 28 and the B seven, once this entire interaction is complete, it can develop into the cytotoxic T-cells, which can directly affect the pathogens. We can directly go and kill the pathogens, um, or the cells. The target cells, so they can directly go and kill the target cells, or they can also develop the memory T cells. So this is kind of the cell mediated part of the adaptive immune system. So it is the cell-mediated part of the adaptive immunity that we discussed or focused on today. And, uh, in the next class, we will, uh, try to understand the humeral part of the immunity. Which is the B-cell mediated. So this was the T-cell mediated, adaptive immune response. And this is the cell-mediated part of that active immune response. In our next class, we will try to describe the B-cell mediated human immune response.
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