this is part 3 for chapter 17 adaptive immunity your immune system protects you from infectious disease and cancer and overall your immune system is composed of two parts the innate immune system and the adaptive immune system the innate immune system is also considered nonspecific because it's against all microbes in general and it encompasses your two lines of defense the first line of defense which is meant to prevent infection and the second line of defense which starts fighting the microbes once they have entered your tissues your third line of defense is your adaptive immune response and this is the immune response that is generated after you have become infected and this involves the t-cells the b-cells and the antibodies I've talked about the adaptive or specific immune response before and just as a reminder there are two parts to it the first part involves the humoral immune response which specifically focuses on the antibodies and the B cells that produce the antibodies and again the humoral immune response is very good at protecting you from viruses bacteria and toxins the second part of your adaptive or specific immune response is the cell mediated immune response and this involves more specifically the T cells and this is what I will be focusing on in this lecture the purpose of your cell mediated immune response is to kill eukaryotic cells and the T cells are responsible for eliminating eukaryotic microbes cancer virally infected microbes and even transplants and in this image this is a t-cell down here this is the T cell and it is inducing apoptosis in a target host cell so the cell could be a cancer cell it could be one of your cells that is infected with a virus or infected with bacteria or it could be a transplanted eukaryotic cell but this is essentially what happens in cell mediated immune response t-cells kill eukaryotic cells when talking about t-cells there are many different types of T cells and the T cells are identified by their CD molecule CD CD stands for cluster of differentiation and these are glycoproteins that are found in the glycocalyx of the T cells and CD molecules there are over 200 different CD molecules and specific ones are used to identify different types of T cells first type of T cell I want to talk about are the T helper cells and these are identified as cd4 cells or sometimes called cd4 positive cells and this T helper cells their main function is to secrete cytokines so they are communicators they receive information and they send information so they receive information in the form of cytokines or interleukins and they release signal molecules cytokines are interleukins to communicate with other cells and in your book it goes over two different types of T helper cells T helper 1 and T helper 2 I'm just going to group them together so we'll just talk about T helper cells in general second type of cell you need to know are the cytotoxic T lymphocytes and these are the cd8 positive cells so cd8 positive and they are cytotoxic these are actually the T cells that will destroy the target cells these used to be called T killer cells so I might call them T killers because that's what they do they kill the target cell and the way they kill the target cell is by secreting a molecule called perforin or friend which perforates the cell membrane so these are not phagocytic cells the only phagocytic white blood cells are macrophages and neutrophils CTLs or T killer cells kill by secreting perforin which induces that apoptosis second type of T cell that I want you to know are the T regulatory cells and their job is to stop the T killer cells once they have completed their job so T regulatory cells turn off the cell mediated immune response and these are identified as cd25 cells cd5 cd25 positive cells also involved in cell mediated immunity are macrophages and I'll talk about those later the last type of cell I want you to know are the natural killer cells and these are very closely related to CTLs but they are involved only in that antibody dependent cell-mediated cytotoxicity which is one of the results of antibody binding to antigen so these are very similar to CTLs except they are nonspecific they need the antibodies to tell them which cell to destroy the next thing I want to do is go through t-cell development so like I went through the B cell development I'm going to talk about T cell development so where they originate what happens when they mature and how they are activated the basic story of a T cell is very very similar to the basic story of a B so so just as a reminder with the life story of a b-cell b-cells developed from stem cells in the red bone marrow and then they mature in the red bone marrow and once they mature they go to the lymph node T cells have a similar life story to the B cells they are also generated by the stem cells in the red bone marrow so that is where they originate but then in order to mature T cells migrate from the red bone marrow to the thymus so that is actually why they are called T cells because it tells you where they mature so they mature in the thymus and the thymus is a small organ that lays right over your heart during maturation B cells went through a specific process called genetic shuffling T cells have their own process called T cell education or T selection T cell education or T cell selection is a very important event that occurs during T cell maturation in the thymus during this process the T cell is going to be tested as to how well it recognizes self molecules compared to non-self molecules so during this time the T cell is going to be tested by thymic cells cells that are found in the thymus and it is being tested to see how well it recognizes self antigens and MHC MHC is going to be an important molecule that I'll talk about in terms of the immune response and MHC our molecules that are found on your own cells so this is one example of a test so the T cell is being tested to see how well it recognizes the self antigen and the MHC molecule in this case this T cell fails to recognize the MA see molecule so it's t-cell receptor t-cell receptor does not interact with the MHC molecule and that is a fail basically so that cell cannot survive so it is triggered to go through a pack apoptosis it does not pass the test a second situation could be where the t-cell is interacting with the thymic cell and it recognizes the MHC and the self antigen so it has the appropriate level of recognition and it is allowed to finish maturing and to survive the last example is where the t-cell over reacts to self molecules so again here is the T cell here is the thymic cell and the T cell is recognizing the self antigen too much so the self antigen is actually stimulating the T cell which means that this T cell would actually recognize self molecules and would overreact and start killing your own normal cells so of course that is too much of a reaction it's an overreaction and those particular T cells would be eliminated by apoptosis so during T cell education or selection the T cells are tested to see how well they react to self antigens in MHC molecules if they fail to recognize this MHC they will be eliminated if they over react to the self molecules they will be eliminated only those that have the right balance where they recognize the MHC but they don't over respond to the self molecules the self antigens those will be allowed to survive so during T cell education or t cell selection in the thymus only those that respond appropriately to hc' molecules will be allowed to survive and finish maturing once they finish maturing they then will migrate to the lymphoid tissue such as the spleen and the lymph nodes just like the b-cells did as a review of the development of the lymphocytes the B cells and the T cells both of them start in the bone marrow derive from the stem cells for maturation b-cells remain in the bone marrow that's why we call them b-cells and during maturation they go through genetic shuffling once they have matured the b-cells will then migrate to the lymph nodes t-cells again start in the bone marrow derived from the stem cells they migrate to the thymus where they go through t-cell education teeth cell selection if they survive that process they finish maturing and then they join the B cells in the lymph nodes once the B cells and T cells migrate to the lymph nodes there they will wait to be activated and each b-cell and t-cell will wait for about 3 months to be activated if they are not activated by the end of the 3 months then they will die by apoptosis for activating B cells and T cells there are two different pathways T independent activation and T dependent activation T independent activation for T independent activation all you need is the antigen so only the antigen is required to activate the lymphocytes this way these cells are the only type of lymphocyte that can be activated T independently and activating b-cells T independently will produce low antibody production and they will only produce class IgM so relatively speaking this is going to be a weaker response than if you activate the b-cells T dependently so T independent activation is what I talked about when I went over B cell activation in the previous lecture when I went through this diagram this was an example of T independent activation so to activate these b-cells all that is needed is the antigen so only the antigen when the appropriate b-cell with the IgD molecule that could recognize that particular antigen when it bound to the antigen the b-cell was activated to go through mitosis to generate genetically identical daughter cells that were either memory cells or plasma cells once the plasma cells arose then they secreted antibody starting first class IgM and then IgG in the case of T independent activation it will only be class IG so these B cells will not switch over to IgG so T independent activation it requires only the antigen and it is only used to activate B cells but if these cells are activated this way you're going to get very low antibody production only class IgM and overall this is a weak response conversely T dependent activation requires a T helper cell and the antigen so T dependent activation you are dependent on the T helper cell and this is a way to activate t-cells and b-cells so all sorts of lymphocytes can be activated this way if the b-cells are activated T dependently then you will get high antibody production and you will produce IgM and IgG and overall this will be a much stronger response t dependent activation is a fairly complicated response it's going to start first with an antigen processing cell like a macrophage that which will activate a T helper cell and then that T helper cell will activate T cells and B cells the first cell involved in a T dependent activation is an antigen processing cell so the antigen processing cell is some sort of macrophage and in this case it's a dendritic cell which is a fixed macrophage so the first process is going to be this phagocytic cell antigen processing cell is going to phagocytose a microbe so it's going to detect the microbe it's going to adhere to the microbe and ingest the microbe so you should review the process of phagocytosis so attachment ingestion digestion and so on now important for the dependent activation is when the macrophage is digesting the microbe it's going to remove antigens from the surface of the microbe so as that microbe is being digested the phagocytic cell is going to remove the antigens then the phagocytic cell is going to put those antigens on to MHC molecules so it's going to put those antigens onto the MHC molecule creating and MHC antigen complex once it has done that it's going to transport that MHC antigen complex to be presented on the outside of the cell so there should be a little antigen on there so that is antigen presentation so a phagocytic cell is going to phagocytose the microbe take antigens off of that micro put those antigens into MHC molecules and then transport that complex to the outside of its self outside surface one Steph a go sit Excel that macrophage has processed the antigen and presented the antigen now it's time for the T helper cell and what they TL per cell is doing is the T helper cell is checking the MHC on the outside of macrophages to see if the macrophage macrophage has found a particular antigen if the T helper cell recognizes the antigen that is presented by the antigen presenting cell then that T helper cell becomes half way activated to become fully activated the T helper cell needs a second signal and we call this the second signal the second signal is il-1 interleukin one that is produced by the antigen processing cell and secreted out so in order to be fully activated the T helper cell needs to be able to recognize antigen that is presented in MHC from an antigen processing cell and it needs to receive the second signal the interleukin 1 once it has received those two signals now the T helper cell is come activated once the t-helper cell has received the first signal of the antigen presented in the MHC and the interleukin 1 secreted by the antigen presenting cell then it is fully activated and a fully activated T helper cell will secrete cytokines specifically in turn Lucan 2 so fully activated T helper cells secrete interleukin 2 which will then diffuse to neighboring T cells and will activate those T cells so T helper cells what T helper cells do is they receive signals from antigen processing cells and they send signals to lymphocytes like t-cells and b-cells and this will cause this T cell to go through mitosis and to generate memory cells memory T cells which will wait for 10 years until the second time your body experiences that antigen and it will also produce effector cells and effector cells are the CTLs that go out and kill the target cells T dependent activation can also activate b-cells so this is the same process just in a different image so here you have your antigen presenting cell it is phagocytose in the microbe it is removing antigen from that microbe and presenting the antigen in MHC molecules the T helper cell is recognizing the antigen in the MHC molecule and it would also receive the Aisle 1 signal from that macrophage to activate a b-cell that activated t-helper cell will secrete il-2 il-2 which will interact with the B cell and activate the B cell that is recognizing antigen and because that b cell has received il-2 that signal that means it will go through clonal expansion and it will divide by mitosis into plasma cells and memory b-cells and this time you will have antibody production from the plasma cells starting with IgM and it will switch over to I G G as a summary of your third line of defense or your adaptive immune response it has two parts first the humoral immune response and second the cell mediated immune response humoral immune response refers to the production of antibodies and that is accomplished by b-cells so your humoral immune response can be T independently activated so you can have antigen directly interact with the b-cells to stimulate or activate the b-cells to go through clonal expansion to generate plasma cells which will produce antibodies and also produce memory cells cell mediated immune response can only be activated T dependently so for this you need an antigen presenting cell some sort of phagocytic cell to phagocytose the microbe present the antigen to a T helper cell also it needs to secrete the aisle one to stimulate the T helper cell that T helper cell will then secrete il-2 which will stimulate the CTLs to go the target cells so the CTLs you are generating again memories t-cells and also the effector cells the effector cells which go out and have the effect of killing the target cells T dependent activation can also stimulate b-cells so this T helper cell once it is activated it can secrete il-2 which will activate the b-cells and create a stronger humoral immune response both of these are going to generate memory cells so at the end you will have memory B cells and memory T cells and both of these memory cells will remain for 10 years