this is part 2 for chapter 17 adaptive immunity chapter 17 is all about your adaptive or specific immune response and this is also known as your third line of defense and your third line of defense involves the lymphocytes the t-cells and b-cells and the antibodies and your adaptive or specific immune response is responsible for fighting a microbe that has infected your body so it is a response to an actual infection for your adaptive for a specific immune response there are two parts the first part is the humoral immune response and the humoral immune response involves mainly the antibodies and the B cells that make the antibodies the second part of your adaptive or specific immune response involves the cell mediated immune response and this more specifically requires T cells and the T cells will go out and kill eukaryotic cells in the previous lecture I talked about antibodies and as a review the basic structure for an antibody is a monomer basically a Y structure and it is composed of four protein chains two heavy chains and two light chains and these are held together by disulfide bonds and every chain has a constant region in a variable region and the variable region of the light chain and variable region of the heavy chain make up the antigen binding site and the antigen binding site has a particular structure that fits perfectly the epitope of an antigen so when the antibody binds to the epitope of an antigen we say the antibody is recognizing that antigen I also went over the five classes of antibody in the first class I went over was IgG IgE G is a basic monomer it has found mainly in the blood makes up 80% of the antibodies found in the blood and it is so small that it can cross into tissues so it can leave the circulation and go into the tissues and an important part about IgG is that it is the second class of antibody made by an activated b-cell the next class of antibody I talked about was IgA IgA is a dimer it's two of those monomers bound together and IgA is found mainly in mucus and other secretions such as breast milk the main purpose of IgA is to prevent attachment the next one was IgM IgM is a really large antibody because it is made of five of those monomer structures an IgM is found only in the blood because they cannot leave the circulation cannot leave the blood vessels and cross into the tissue tissues an IgM is responsible for transfusion reactions the last 2 IG D and IgE are monomers in structure but they act as cell receptors IG D is on the surface of B cells B cells and when it binds to its appropriate ancient antigen it serves to activate the B cells IgE is found on the surface of mast cells and basophils and mast cells and basophils when the IgE binds to the appropriate antigen it will serve to activate the mast cell and the basal fill and both of these will release histamine which stimulates inflammation so these are the five classes of antibody and one particular B cell is able to produce all five class then I went over the five results of antibody binding to antigen or the five benefits of antibody binding to antigen so the five things that will help fight an infection the first results of antibody binding to antigen is agglutination because every antibody has at least two antigen binding sites that means that mixing antibodies with the microbes you will get clumping of the microbes and this prevents the spread of the microbes through your body IgM is really really good at agglutination the next result of antibody binding to antigen is activation of complement so activation of complement every antibody has complement binding sites on the constant region of the heavy chains so this is the classical pathway of complement activation when you have an antibody bound to the microbe that activates complement and complement activates in a cascade manner so once you activate one one complement protein you will have many proteins activated and that will lead to opsonization triggering of inflammation and direct lysis of the microbe third benefit of antibody binding to antigen is optimization basic definition of optimization is when a microbe is coated with an antibody in this case the antibody sorry when a microbe is coated with a protein in this case the protein is the antibody when you have opsonization it makes it much easier for the phagocytic cell to bind to the microbe and phagocytosis fourth benefit of antibody binding to antigen is neutralization neutralization means that when the antibody binds all over the virus it prevents the virus from binding to cells so that neutralizes the virus it will not be able to infect the cells if antibody binds all over a bacterium it prevents it from adhering to the tissues of the human and then that microbe can be flushed away or washed away for exotoxins if antibody is bound all over the exotoxin then the exotoxin cannot affect the target cell last benefit of antibody of antibody binding to antigen is antibody dependent cell-mediated cytotoxicity and this is where the antibody binds to a eukaryotic microbe and that signals to other white blood cells that they need to destroy this organism so the antibody dependent cell-mediated cytotoxicity the antibody is basically tagging different organisms so that the other white blood cells know they need to eliminate it the rest of the lecture is going to be over B cell development and B cells are important because they are the white blood cells that actually produce the antibodies so I'm going to talk about where B cells come from how they mature and how they become activated to actually start producing antibodies B cells like all leukocytes they are derived from stem cells that are found in the red bone marrow so that is where a B cell begins its life it is derived from the stem cells and it is found in the red bone marrow after the B cell is formed the B cell has to go through maturation and B cells mature also in the red bone marrow and that is basically why B cells are named B cells because it tells you where they are maturing they are maturing in the red bone marrow during maturation there is a really important event that occurs and that is called genetic shuffling genetics shut wayne is an important event that occurs during the maturation of b-cells and the genes that are actually being shuffled and randomly selected are the genes that encode the variable region for the heavy chain and the variable region for the light chain so genetic shuffling is going to determine the shape of the antigen binding site for the antibodies produced by a particular b-cell and the shape of the antigen binding site is going to determine what epitope is recognized this image will help you understand genetic shuffling better at the bottom is an image of an antibody so here are the two identical heavy chains here are the two identical light chains and these colored regions represent the variable region of the heavy chain and light chain so going through first the heavy chain this is the variable region and for the variable region there are actually three sub regions so AV region which is represented by the red Square D region which is by the blue hexagon and a J region the green circle every heavy chain variable region has 1b region 1d region and one j region but for the V region there are over 79 options for the structure of the B region so there are 79 possible genes that you can select from to determine the shape of the V region for the D region there are 12 different genes and you would select one for the J region there are four options for the genes for the structure of the J region so during genetic shuffling it is randomly determined which of these genes will actually encode for those regions so for instance for one particular b-cell is randomly determined that v4 will be selected so v4 is selected to encode the structure for the B region and maybe d2 is randomly selected to encode for the D region and maybe j1 is randomly selected so those are the three genes that are randomly selected to form the structure of the variable region and once they are selected they never change same thing happens for the light chain except for the light chain there are only two regions there is a V region with a hundred options and there is a J region with five options so in this case maybe V 98 is selected and maybe J 5 is selected so again this is a random process that's why it's called genetic shuffling the shuffling implies that it is random but once it is selected then all the antibodies produced by that particular V cell will have exactly the same structure their antigen binding site will be exactly the same for both antigen binding sites on one ant body and all the antibodies will recognize exactly the same epitope of an antigen so the B cell arose from the stem cells in the bone marrow it's remained in the bone marrow to mature during maturation it went through genetic shuffling which will determine which epitope the antibodies of this particular V so will recognize once the B cell has finished maturing then it is going to migrate to the lymph nodes and also the spleen so all the B cells once they have matured they migrate out of the bone marrow and go to one of the lymph nodes or the spleen and there they wait to be activated so as I mentioned once a b-cell matures it goes to the lymph node and it will wait to be activated and on average b-cells will wait for about 3 months in the lymph nodes until they are activated if they are not activated then they will die off but if they are activated then they will go through the following process so b-cells again start from the stem cells in the bone marrow they go through maturation during maturation they go through genetic shuffling where it is determined what antigen their antibodies recognize once they have matured then those b-cells go to a lymph node so here is an example of four different B cells that are waiting in the lymph node and every b-cell has a different antigen binding site on the antibodies so remember these antibodies if they're in the cell membrane they are IgD so this B cell be cell number one recognizes around antigen B cell number two recognizes a square antigen B cell number three recognizes a triangular antigen and B cell number four recognizes an inverted antigen for instance so these four B cells along with actually thousands of other b-cells are waiting in the lymph nodes for an antigen to filter through an antigen that entered the tissues and was flushed out of the tissues into the lymphatic vessels and is now being transported to the lymph node so those B cells are waiting for an antigen that they can respond to and B cell number three apparently has an IgG molecule that can recognize this particular antigen once a b-cell comes in contact with the antigen it is specific for then that b-cell will be activated and when a B cell is activated it's going to go through a process called clonal expansion so it is going to divide by mitosis to form daughter cells genetically identical daughter cells so that means all of the daughter cells are going to have exactly the same antigen binding sites as the original activated b-cell the first type of daughter cells that the activated b-cell are going to form our memory cells memory cells ourselves that are going to wait in the lymph node and will activate the second time the body comes in contact with this particular antigen and these memory cells are going to wait for 10 years if they have not been activated in 10 years then they will die so an activated b-cell is going to go through clonal expansion dividing by mitosis to form memory cells which will wait for 10 years and the other type of daughter cells will be plasma cells and the vast majority of the daughter cells will be plasma cells and the plasma cells are the cells that actually produce the antibody so they're called plasma cells because they will be secreting the antibody into the plasma in here the plasma cells are secreting antibody into the plasma into the blood and as you remember it the first class of antibody that they will be secreting is IgM and after a few days they're going to switch to I gg so in this diagram you can see that one particular b-cell is able to make 3 different classes of antibody so all the b-cells start with IgD and if they are activated can secrete IgM and then switch over to IgG related to your third line of defense is the idea of primary and secondary responses a primary response is the first time you come in contact with a particular antigen and the secondary response is the second time you come in contact with a particular antigen primary response in the primary response in terms of b-cells it's it is an a naive b-cell that is being activated a naive b-cell has never been activated before that's what naive means no experience so in a primary response it involves a naive b-cell being activated so with that naive b-cell the first class of antibody it's going it's plasma cells are going to produce is IgM and later it will switch over to IgG a few days later also this process takes a relatively long time it takes about 10 days and that's because it takes time for the antigen to enter into your tissues to get flushed from the tissues to go through the lymphatic vessel to get to the lymph node to get to a b-cell that responds to it and then those B cells have to go through mitosis and for eukaryotic cells mitosis can take between eighteen and twenty hours and what's once that happens then the plasma cells have to start secreting the antibody first the IgM than the IgG all of this takes time so a primary response takes a long time and relatively speaking a primary response is fairly weak but the important thing about the primary response is that at the end of this you're going to generate memory b-cells so that's the important end product of the memory visa are the memory b-cells and they will wait around for 10 years in your lymph nodes secondary response a secondary response is the second time you come in contact with a particular antigen and if it is within those 10 years you are now activating memory b-cells and most of the time it's more than one cell because for every naive b-cells you generate about 50 memory B cells and memory b-cells are experienced they've been activated before so a memory b-cell will right away start producing IgG and will still produce the IgM so right away you have i GG being produced and it takes a relatively short time only about 2 to 3 days to get significant levels of antibody being produced and this is a very strong reaction because you have more than one b-cell being activated and you're producing IgG right away and high levels of IgG usually a secondary response is so fast and so strong and because you get a GG being produced the IgG can go straight into the tissues to the site of infection right away so because of all these things usually secondary responses are able to clear the infection before you get signs and symptoms so usually a secondary response is able to clear the infection before you get the disease and with when this happens we say the person is immune so if somebody is immune to a particular disease that means that they can still be infected but they'll have a secondary response which will be so fast and so strong it clears that infection before they get the disease this is a diagram that shows you what is happening during a primary and secondary response the x-axis is time in days and the y-axis is the concentration the level of antibodies in the serum so at x 0 this is when the person is first exposed to the antigen and there isn't any significant antibody production until about 10 days and first to peak is the IgM and then it takes a little bit longer till you get significant numbers of IgG but at the end of this you generate memory second exposure to the antigen so this is the beginning of a secondary response so sometime later there's a second exposure to the antigen and now you're going to have a secondary response which is going to happen much more quickly and first IgG you're going to get extremely high concentrations by G G and you still get the IgM being produced but the high concentrations of IgG are going to clear the infection before you actually get disease adaptive immunity adaptive immunity is where a person develops the ability to be immune to a particular disease and there are four types of adaptive immunity understanding adaptive immunity you have to understand the four different terms that are involved in the definition and the first two sets of terms are naturally acquired adaptive immunity and artificially acquired adaptive immunity so natural and artificial natural means that this immunity is acquired in a natural way part of the normal experience artificial means that there is medical intervention which usually means there's some sort of injection so those are the first two terms you need to know naturally acquired immunity and artificially acquired immunity the second two terms the next two terms are active and passive active immunity means that the white blood cells are exposed to an antigen they go through the process of activation they go through clonal expansion and they generate memory passive immunity involves just the transfer of antibodies naturally acquired active immunity is basically being naturally exposed to antigens like being naturally infected inhaling a respiratory microbe ingesting a microbe having been bitten by a mosquito having the microbe injected into your body so in a natural way your body is exposed to an antigen and then it goes through a normal response passive immunity is a natural way where antibodies are transferred from one person to another and the only natural process for that is from a mother to a fetus or a baby so a mother can transfer antibodies to her baby baby in two different ways IgG can cross the placenta and go into the fetuses circulation and IgA can be transferred to the baby through breast milk so this is naturally acquired active immunity naturally acquired passive immunity for artificially acquired immunity artificially acquired immune can be active or passive artificially acquired active immunity means that we are injecting antigens into the person's body to activate that person's own lymphocytes and generate memory and an example of this is vaccination so that's exactly what is happening during vaccination medical personnel are injecting antigens into the individual's body to generate memory and then of course the idea with vaccination is that if the person is actually exposed to the pathogen they will have a secondary response right away so that they can clear the microbe before they get the disease passive artificially acquired passive immunity this is where you are infusing antibodies into an individual and these usually this is an immuno compromised patients people getting chemotherapy or have other immuno compromising conditions and we take antibodies from other people and inject them into the person the most common form of this is gamma globulin gamma globulin is IgG that has been acquired from other people alright so adaptive immunity has two types naturally acquired immunity and artificially acquired immunity and both of these have an active form and a passive form the important thing about the active forms of acquired immunity is it's going to generate memory passive immunity there is no memory because you've just transferred antibodies and the immunity only lasts as long as the antibodies last an i GG will last about 3 months IgA lasts for about a month