0:00 So, here we have a lymphoid precursor cell, which enters the cortex area of the 0:14 thymus, 0:16 right? 0:17 And it moves in through the blood vessel, so a lymphoid precursor cell. 0:21 Now, this lymphoid precursor cell, as I said earlier, is going to mature to 0:27 become a T cell. 0:29 However, the lymphoid precursor cell expresses no signs of being a T cell on 0:35 its surface, 0:37 so it doesn't express a CD4 or it does not express even a CD8 co-receptor. 0:42 That is why we call this lymphoid precursor a double negative, because it 0:47 contains no 0:48 CD4 or CD8 co-receptor, which is required for a T cell. 0:55 The thymic epithelial cell will assist the development of this lymphoid 0:59 precursor cell 0:59 throughout the cortex to become a T cell, a CD4 T cell or a CD8 T cell. 1:06 Now, this lymphoid precursor is in stage one, also known as double negative one 1:13 . 1:13 After some time with the help of the thymic epithelial cell, it will become a T 1:18 cell precursor, 1:20 double negative two, where it loses its ability to become other type of lymph 1:26 ocytes, such 1:27 as a B cell. 1:28 So in the double negative two stage, it has already lost its ability to become 1:32 other 1:32 types of cell, such as a B cell or a natural killer cell. 1:37 So it's destined to become a T cell for sure. 1:41 This precursor T cell is in the double negative two stage, where it also begins 1:46 to slowly 1:46 express the T cell receptor, but it still does not express the CD4 or the CD8, 1:52 hence 1:53 double negative. 1:55 Again after some time with the help of the thymic epithelial cell, the 1:58 precursor T cell 1:59 will become a thymocyte, which is still an immature T cell, and this stage is 2:04 double 2:04 negative three, which means that it still does not express CD4 or CD8 co-re 2:09 ceptor, but 2:10 it has expressed the T cell receptor. 2:14 Right after some time, it enters the double negative four stage. 2:20 And during this stage, the thymocyte will begin to proliferate, meaning it will 2:24 begin 2:24 to make many thymocytes, and with the appropriate chemical signals, cytokines, 2:31 this thymocyte 2:32 will become a double positive, meaning that it will express both CD4 and CD8 co 2:39 -receptor, 2:40 as well as the T cell receptor that was previously expressed. 2:43 Now, what is the fate of this double positive thymocyte? 2:48 Well, it can die due to neglection if the thymic epithelial cell does not 2:53 interact with 2:54 it, and interestingly enough, this is what usually happens to the thymocytes, a 2:58 majority 2:59 of them die, but we won't talk about that. 3:03 Now alternatively, this double positive thymocyte can interact with an epit 3:09 helial, a thymic epithelial 3:11 cell. 3:12 The thymic epithelial cell expresses an MHC receptor on its surface. 3:17 MHC stands for major histocompatibility complex. 3:21 The thymic epithelial cell can either express MHC class one or MHC class two. 3:28 Depending on what MHC receptor the double thymocyte will interact with, causes 3:35 will cause the thymocyte 3:37 to become a single positive thymocyte, either a CD4 or CD8 thymocyte. 3:46 So for example, if this double positive thymocyte interacts with MHC class one 3:50 receptor, this 3:51 double positive thymocyte will become a single positive CD8 thymocyte, or 3:58 alternatively, 3:59 if this double positive thymocyte interacts with MHC class two receptor, this 4:04 double positive 4:05 thymocyte will become a single positive CD4 thymocyte. 4:10 Either way, the double positive thymocyte will become a single positive thym 4:15 ocyte. 4:16 Now of course if this double positive thymocyte does not recognize our own 4:22 antigen in that 4:23 it thinks our own body is a foreign object, this thymocyte will be destroyed 4:28 through apoptosis 4:30 because we don't want to activate a T cell that thinks our own body is a 4:36 foreign antigen 4:37 because it will start attacking it. 4:39 And so these type of double positive thymocyte that recognizes our body as a 4:42 foreign antigen 4:42 will be destroyed through apoptosis. 4:45 Now these single positive thymocytes are also known as naive T cells, either 4:48 naive CD4 4:49 or naive CD8 T cells. 4:52 And they can interact with dendritic cells in the medulla of the thymus. 4:56 The T cells can scan for antigens on the dendritic cells to become activated. 5:01 So if dendritic cell can express an antigen on an MHC, and then the T cells can 5:07 interact 5:08 with it to become activated. 5:09 But this does happen, but only when a pathogen has invaded the body, and so 5:15 with this the 5:16 dendritic cell can then present the antigen of the pathogen to the naive T 5:20 cells in the 5:21 thymus so that the naive T cells can be activated much more faster. 5:26 However, if there is no invasion and the naive T cells have already been 5:31 produced, they will 5:32 just migrate, they will leave the thymus and migrate elsewhere. 5:37 So the single positive CD4 and CD8s will actually migrate to the peripheral 5:42 lymphoid 5:43 organ through the blood vessel. 5:47 So here leaving the thymus, we have the naive CD4 and naive CD8. 5:52 And they will migrate to the peripheral lymphoid organs. 5:55 What is a peripheral lymphoid organ? 5:57 Well, a lymph node is a good example. 6:00 And so these naive T cells will migrate from the thymus into the lymph node 6:06 here, as shown. 6:07 And remember, in this area we also have the immature B cell migrating to the 6:11 lymph node, 6:12 because this is where the immature B cell also gets activated. 6:17 So let's learn some important areas in the lymph node. 6:21 This middle area here towards the archery in the vein is known as the medulla, 6:26 the lymphoid 6:27 medulla. 6:28 And it consists mainly of plasma cells. 6:31 It's actually densely packed with other cells such as macrophages as well. 6:37 Then to the outer area, we have what's called the paracortex. 6:40 And this is where most of the T cells are situated. 6:44 And then further towards the outer side of the lymph node, we have the cortex. 6:52 And the cortex consists mainly of the B cells. 6:56 And also within the cortex, we have follicles and germinal centers, where B 7:02 cells maturing 7:03 or become activated in. 7:05 And then we have the afferent lymph vessel, which brings certain cells into the 7:10 lymph node. 7:11 And then we have the efferent lymph vessel, which brings cells out of the lymph 7:16 node, 7:16 the activated lymphocytes, for example, the activated T and B cells, for 7:20 example. 7:21 And we'll look into this soon enough. 7:23 Now, let's just take a cross section or a section within the lymph node here 7:28 and zoom 7:28 into this area. 7:38 So over here, we have the lymph vessel circulating within the lymph node. 7:41 And here situated here is the cortex, the outer part of the lymph node with the 7:45 follicles 7:45 and germinal centers here in orange. 7:47 And then we have the paracortex in the middle and the medulla in the inner 7:50 aspect of the 7:51 lymph node where the artery and veins come through. 7:56 So the naive T cells, which came from the thymus, will enter the lymph node 8:02 into the 8:02 paracortex through the blood vessel, through what's called the high endothelion 8:08 venule. 8:10 And this process is through diapodeces, how it enters. 8:14 So the naive CD4 and CD8 cells enter the lymph node and are positioned or are 8:19 situated 8:20 in the paracortex. 8:21 And then we have also the immature B cell, which came from the bone marrow, 8:24 right? 8:25 And the immature B cell, which only expresses IgM, and possibly IgD now, goes 8:30 to the cortex, 8:31 which is where most of the B cells are situated. 8:35 And remember, both the naive T cells and the naive B cell, the immature B cell, 8:39 they 8:39 are not activated. 8:41 They have not been stimulated or activated by any form of chemicals or signals. 8:47 And so we'll just leave them in the lymph node for now, and we'll go back to 8:52 where our 8:52 tissue was and where our innate immune cells are. 8:58 And in the next video, we'll see what happens when a pathogen invades the body 9:01 and how the 9:02 innate immune system responds, just an overview sort of thing. 9:07 So that's the next video. 9:09 Thanks for watching.
