Immune Tolerance

in this video, we're going to begin our lesson on immune tolerance. And so what's important to note is that our immune system must be able to build what is known as immune tolerance in order to prevent an inappropriate response of our immune system to harmless antigens. And so immune tolerance can be defined as the ability of our immune system to ignore or in other words, to tolerate any given molecule. And so really the goal of immune tolerance is to generate immune tolerance to only harmless antigens. And so in other words, we only want our immune system to ignore harmless antigens. And we don't want our immune system to ignore dangerous or harmful uh antigens. And so without immune tolerance, our immune system would have a really hard time distinguishing between harmless and harmful. And so that would leave our immune system more likely to attack our own healthy uninfected cells, leading to diseases known as auto immune diseases. And we'll get to talk more about autoimmune diseases later in our course, in a different video. Now, if we take a look at our image down below, we can get a better understanding of immune tolerance, which is really the ability for our immune system to distinguish harmless antigens from harmful antigens. And so notice here, what we have in the middle is one of our adaptive immune system cells, perhaps a T cell or a T cell here. And so notice that this T cell has learned to tolerate all of the things that are listed over here on the left, which include the normal micro flora or normal microbiota, normal self cells or our own healthy cells, as well as other harmless antigens. And so it's the harmless antigens that are immune system has built a tolerance for. And so immune system tolerance is built towards harmless antigens and notice that this again immune system cell in the middle of this T cell has not built a tolerance towards these harmful antigens and pathogens, including pathogens, cancer cells that are infected and also other harmful antigens as well. And so ultimately what we're saying here again is that immune system tolerance is the ability for our immune system to distinguish harmless from harmful and to practically ignore all of the harmless substances but attack all of the harmful substances. And so this year concludes our brief intro to immune tolerance and we'll be able to continue to learn more and more about it as we move forward in our course. So, I'll see you all in our next video

in this video, we have a football analogy for immune tolerance. And so first we need to recall from our previous lesson video that immune tolerance is the ability for our immune system to distinguish between harmful and harmless antigens. And so here, in this football analogy, the immune system is represented as the QB or the quarterback of the team, and the harmful antigens are represented as the opponent team, and the harmless antigen are represented as the teammates. Now without immune system tolerance, then our immune system cannot distinguish between harmful and harmless antigens. And that means that the immune system will not be able to perform its job very well. And so if we take a look at our image down below at our football analogy, notice that without immune tolerance then our immune system will be unable to distinguish harmful from harmless substances. And so that means that our immune system represented as the QB QB immune system here is going to be unable to distinguish his teammates from the opposing team. And so notice that all these players are on the field. However, the QB which is representing our immune system cannot distinguish between the harmful and harmless substances and what that means is because the QB can't figure out who's on his team, he's not going to be able to do his job properly. And so without immune tolerance, the immune system cannot do its job properly and it could lead to autoimmune diseases. Now, on the other hand, with immune system tolerance or immune tolerance, then our immune system can distinguish between harmful and harmless substances properly and that means that our immune system will be able to perform its job properly. And so, if we take a look at our image on the right hand side over here, notice it's representing with immune tolerance, that means that our immune system will be able to distinguish between harmful and harmless substances, which means that our QB here our QB immune system will be able to distinguish his teammates from the opposing team. And so notice here that his teammates are all colorful, and because the QB can distinguish the teammates from the opposing team, the immune system will be able to perform its job properly. And so I noticed the QB is saying, oh, now that I have immune tolerance, I can do my job properly. And so, really, the analogy here, the football analogy goes to show how immune tolerance allows our immune system to distinguish harmful from harmless substances, and again, to be able to do its job properly and only build immune tolerance towards harmless substances and target and attack harmful and dangerous antigens. And so this here concludes our football analogy for immune tolerance, and we'll be able to get some practice applying these concepts and learn even more about immune tolerance as we move forward in our course. So, I'll see you all in our next video

in this video we're going to introduce and differentiate central immune tolerance and peripheral immune tolerance. And so what's important to note is that sometimes our adaptive immune response can make a mistake and it can mistakenly produce what are known as self reacting T. And B cells. And so self reacting here just means that these T. And B cells will react to our own self cells that are healthy and uninfected. And so these self reacting T. And B cells will actually harm our own healthy cells which is a bad thing. And again this is a mistake that our adaptive immune system can do occasionally. And so in order to prevent this mistake from happening, our body has to be able to build up a tolerance by strictly controlling T. And B. Cell development to make sure that these self reacting T. And B cells are not produced. And so really there are two types of tolerance mechanisms that control T. And B. Cell development. And those two types of tolerance mechanisms are central immune tolerance and peripheral immune tolerance. And so central immune tolerance is going to occur via negative selection of mature T. And B cells before leaving the primary lymphoid organs. And recall that the primary lymphoid organs include the bone marrow for the B cells and the thymus for the T cells. And so this negative selection of the maturity and B cells involves the elimination or the removal of the self reacting uh T. And B cells by apoptosis, essentially killing any cell that binds self or harmless antigens. Now, peripheral immune tolerance on the other hand involves the selection of mature T. And B cells after leaving the primary lymphoid organs and making their way to the secondary lymphoid organs. And so uh peripheral immune tolerance involves both negative selection as well as positive selection. And so uh peripheral immune tolerance will positively select T cells that bind any MHC. So it will positively select for um T. And B. Cells that bind their antigen. Uh and it will negatively select T cells that bind harmless antigens. And so positive selection refers to promoting cells that do something. Uh And negative selection refers to inhibiting or killing cells that do something. Um And so we'll be able to distinguish that a little bit better down below When we get to this interesting image of jigsaw from the scary movie saw. Now these self reacting T. And B cells they will actually become a nerd GIC or unresponsive uh and eventually they will undergo apoptosis again uh negatively selecting for those T cells that bind harmless antigens. And so between these two tolerance mechanisms, central tolerance and peripheral tolerance. These tolerance mechanisms are so strict that approximately 95% of all of the T. And B cells that we initially create are going to undergo apoptosis. And only 5% of the T. And B cells will be able to make it through these tolerance mechanisms. And so that means that that that small percentage that small 5% of the T. And B cells that make it through are going to be very effective at doing their job appropriately and targeting harmless harmful antigens appropriately. And so if we take a look at this jigsaw down below, we can better distinguish between negative selection and positive selection. So negative selection as its name implies, is going to involve something negative here and that is uh if you do this, whatever this may be, then you die. And so negative selection means that it's going to be killing or eliminating cells that do something specific. And in the case that we're talking about here, negative selection is going to be applied to T. And B. Cells where if the T. And B cells bind to harmless and self antigens then they will die. That is negative selection. Now positive selection on the other hand is somewhat positive. If you do this, whatever this may be, then you get to survive. And if you don't do it and then you die. And so positive selection involves reinforcement for uh something that is happening. And so in the case that we're talking about here, positive selection is going to be promoting and allowing cells that bind any MHC uh to proceed forward and survive. And so will also be able to apply this down below in this other image that we have as well. And what you'll notice about this image is that it's focused specifically on T cells. Um but of course the concepts that we're talking about here applied to both T cells and B cells. And so notice on the left hand side of this image over here we're focusing on central tolerance um occurring before the immune cells leave the primary lymphoid organs. And for T cells that would be the thymus. So central tolerance for T cells occurs in the thymus. And then on the right hand side of our image, we're showing you peripheral tolerance after the immune cells leave the primary lymphoid organs and go to secondary lymphoid organs such as the lymph nodes for example. And so what's important to note is that central tolerance uh is going to involve negative selection, meaning that if cells do something they will be eliminated and that something in this case is going to be bind to self antigens. And so notice that on the far left over here we have a bunch of T cells. Okay. And which you'll notice is that there are a total of six T cells that are right here at this position and all of these T cells are initially produced and developed within the tinus. Now, before all of these t cells leave the thymus central tolerance will uh take place. And central tolerance involves negative selection. So any T cell that binds to harmless or self antigens will be eliminated via apoptosis. And so notice that most of the self reacting T cells here are going to be eliminated via apoptosis. And that is a good thing again, we do not want self reacting T cells. And so it's a good thing that our self reacting T cells are being eliminated here. However, sometimes negative selection can fail. And so what that means is that sometimes a self reacting T cell is not going to be eliminated and it will be able to leave the primary lymphoid organ. But notice that uh these T cells down below right here are not self reacting T cells. And so because they're not self reacting T cells, they are not going to be eliminated and they will be able to leave the primary lymphoid organs. Now, after these T cells, this one right here and these two down here after they leave the primary lymphoid organs, they will be exposed to peripheral tolerance mechanisms in the secondary lymphoid organs and peripheral tolerance mechanisms involves both positive and negative selection. Now, positive selection once again is going to be um if you do this then you get to survive and this in this case is going to be bind to the appropriate antigen. Uh And so what you'll notice here is that um this uh t cell over here is going to bind sufficiently to an MHC and because it binds sufficiently to an MHC, it will be able to be promoted and survive. And the same goes with this one right here, it's sufficiently binds and recognizes antigens on MHC. So it again gets to survive and be promoted. Now notice that the one that's down here has insufficient recognition of MHC. And so because it does not sufficiently bind and recognize uh it is going to be eliminated. However, the cells that do sufficiently bind the cells that do something and sufficiently bind are promoted. And so that's why it's positive selection. If you do this, you survive. If you don't do this then you don't survive. Now, after these cells are exposed to positive selection, then they will be exposed to negative selection. And so again, cells that do something are going to be eliminated. And so in this case this cell is self reacting. And so in uh this peripheral tolerance it's going to be exposed to more um harmless self antigens. And again, when it is going to respond to harmless self antigens, it will become a nerd chick and ultimately undergo apoptosis. And so the Big Red Xs here represent, it's going through apoptosis. Uh now this cell right here notice that it is going to recognize and respond to harmful viral antigens in this case. And because it is responding appropriately to something that is harmful, it is going to be able to proceed forward and survive and ultimately generate an immune response. And so what you'll notice here is that in the very, very beginning we had a total of six T cells that were produced. However, of these 60 cells, only one of the T cells is able to make it through both central and peripheral tolerance mechanisms and generate an immune response. So only a small person percentage of all of the T cells and B cells that we produce are actually going to make it through the central and peripheral tolerance mechanisms to be able to generate an immune response. And so the T cells and B cells that we do have in our secondary lymphoid organs are going to be ones that have undergone these strict tolerance mechanisms and are going to be capable of generating uh an appropriate immune response. And so this year concludes our brief lesson on central versus peripheral tolerance mechanisms and we'll be able to get some practice applying these concepts as we move forward in our course. So I'll see you all in our next video.

The most important function of peripheral tolerance is to:

• A. Eliminate mature B & T lymphocytes that bypassed central tolerance from reacting to self-cells.
• B. Eliminate inactive B & T lymphocytes from peripheral blood.
• C. Eliminate self-reacting B & T lymphocytes before they enter central tolerance.
• D. Eliminate mature B & T lymphocytes from the bone marrow.

Where do T cells undergo central tolerance selection?

• A. Bone marrow.
• B. Pancreas.
• C. Thymus.
• D. Liver.
• E. Brain.

What is immunological tolerance?

• A. The ability of the immune system to remove lymphocytes that recognize and attack foreign antigens.
• B. The ability of the immune system to differentiate between self and non-self antigens.
• C. The ability of the immune system to create antibodies that most effectively bind foreign antigens.
• D. The ability of the immune system to tolerate a certain amount of pathogens before triggering an immune response.

Which of the following is NOT a consequence of the immune system lacking an immune tolerance?

• A. The immune system cells will only recognize and attack foreign antigens.
• B. The immune system cells will recognize and attack foreign and self-antigens.
• C. The immune system will attack self-cells causing autoimmune diseases.
• D. The immune system will not remove T and B lymphocytes that bind to self-antigens.