so for the final part of this chapter we are going to be covering something known as monoclonal antibodies so before we talk about the monoclonal antibodies we will start off with the situation let's say for reasons which I'll explain later we would like to have a large scale production of a particular type of antibody there can be many reasons why we want to do that but what I want you to understand here is when I say large scale production I don't mean this is going to be happening in our body uh we want it to be industrial industrial meaning to say it's going to be artificial we might have to use uh you know certain types of fermenters technology to produce these type of antibodies why I will explain it later but for now I just want you to understand that we can use monoclonal antibodies for the diagnosis or the detection of some diseases and we can also use monoc colal antibodies for the treatment of certain types of diseases so in our body under normal circumstances it is the plasma cells that produce antibodies and yes while the plasma cells can produce a lot of antibodies it's not enough I want more we would like to have more antibodies so the question over here is is there a way for us to artificially produce a lot of antibodies without relying on our body itself and the answer is yes let's talk about these monoclonal antibodies a little bit clonal in this case just means clone or identical cells and mono just means one so when we talked about B lymphocytes in the previous video I told you that our body has many clones of B lymphocytes which means to say they are genetically identical but do you notice any differences in the B lymphocytes over here yes the B lymphocytes each of the B lymy while they are genetically identical they actually have different types of receptors on their surface and those receptors were the ones that were complementary to specific antigens now when we talk about monoclonal antibody I am only wanting to focus on one of the Clone which I have circled over that so why are we focusing on that one well we just want that particular bosy to produce the specific antibodies and look at the shape of the antibodies those are the specific antibodies that I want produced at the large scale so how do we do that the steps of monoclonal antibody production or Maps some books will just refer to monoclonal antibody as Maps okay it's just a short and formed of it um the way to produce it is as follows first thing first we want want the B lymphocytes to become plasma cells right and the only way the B lymphocytes can become plasma cells is it must first undergo clonal selection and where it will bind together to these specific antigens which are complementary so they will respond to the antigens and then they'll undergo clonal expansion so the first step in monoclonal antibody production is as follows you take an injection or a slinge you take a slinge and you fill it up with the specific antigens and look at the shape of the antigens and what we do with this is we inject it into a rodent or a mouse or a small mammal now remember mice are mammals and they also have immune systems quite similar to humans so in the mouse what exactly will happen so the antigens which were injected into the mouse will bind to the specific B receptor and the B lymphocytoid of the mice under goes clonal expansion they will undergo repeated mitosis to produce two types of cells which are the plasma cells and also memory B lymphocytes but here you must understand that we only want to focus on the plasma cells that is the those are the cells that we want why do we only want the plasma cells it is because the plasma cells are the ones that can produce antibodies that is why now so what we do is the plasma cells will then be extracted from the mouse now I'm not going to go into the detail of how the plasma cells are extracted from the mouse uh you don't want to hear it so let's just skip that step okay so you just have to know that once the plasma cells are produc used it will be removed from the mouse okay now we have a problem here the problem with the plasma cell is it can produce antibodies but they don't live for very long in fact they only live for a few days so even if you give them enough nutrients they are only able to survive for a few days and yes while they produce antibodies you will not be able to get a lot of antibodies out of it uh so then some students might say oh well maybe we can make the plasma cells undergo mitosis here's another problem plasma cells cannot undergo mitosis at all once they specialized to become plasma cells they will just be producing antibodies until they die that's the issue so scientists have decided to fuse the plasma cells together with cancer cells now you might be thinking why the hell would C scientists do that see here's the thing plasma cells have a characteristic where it can produce antibodies and cancer cells have a characteristic where they can keep on dividing by mitosis so what scientists will do here is scientists will fuse these two cells together through electrofusion you don't have to know that in detail but in this case over here the reason why we fuse them together is because we want to get cells that can keep on dividing continuously like cancer cells but they can also produce antibodies at the same time like plasma cells so you want the best of both worlds so the plasma cells are fused together with the cancer cells and they will produce this type of cells known as hybrid cells hybrid meaning to say a mix of the plasma cells and the cancer cells om just means pertaining to cancer cells so hybridoma cells are just basically a mix of the plasma cell and the cancer cell that's all it means all right so it produces many different types of cells and the cells are then put into the specific type of Wells I'm going to show you the picture of the well over here and each of the well will only contain one cell now what the scientist will do in this case over here is the scientist will have to identify the hybridoma cell that is the most suitable for example the first hybridoma cell even though it was produced by fusing plasma cells and cancer cells together for some reason that hybridoma cell cannot divide by mitosis and it cannot produce antibodies do we want that hybridoma cell no we don't want that the second hybridoma cell as an example it can divide by mitosis but the problem is it cannot produce the antibodies that we want so we don't want that hybridoma cell either the third one it cannot divide but it can produce antibodies we don't want that to the fourth hybridoma cell however when the scientists examine it they found out that that Homa cell can divide by mitosis that's good and they can also produce these specific antibodies that we want so we have the best of both worlds so the correct hybridoma cell is identified and cultured when I say cultured it just means it is grown in the laboratory to increase the number of cells it is being given a lot of nutrients and whatever substances necessary for it to undergo mitosis so this is good because when you have that specific hybridomas cell that hybridoma cell can divide by mitosis and when it divides by mitosis it produces many genetically identical cells and each of those cells can also produce antibodies and they will produce a little bit of antibodies and those cells will continue to divide the newly divided cells will continue to produce antibodies constantly and in this case you now have a specific type of cell that can undergo cell division and unlimited amount of times and they can also produce the specific type of antibodies at a very large scale so this is how monoclonal antibodies are produced but then comes the more important question what can we actually do with these antibodies one application of monoclonal antibodies is in diagnosis now the meaning of diagnosis is just the identification or the detection of a disease like for example for example remember during uh the covid outbreak we would do something called the rapid test and the rapid test is able to diagnose whether you might have covid-19 or not so that's an example of diagnosis by the way so how can we use monoclonal antibodies in diagnosis as an example over here we can actually use monoclonal antibodies to detect blood clots in our body now what exactly is a blood clot you see just drawing out a leg and in our leg we have multiple veins now as an example the vein in our legs may have a blood clot blood clots are just basically when the blood cells tend to Clump together under normal circumstances blood clots are helpful because they prevent bleeding but sometimes these in this situation here this blood clot is quite dangerous because this blood clot is stopping the blood from flowing inside your vein now one of the treatment of blood clots is the surgeon would have to do an operation where they have to cut open the person and remove the clot manually but the surgeon has to ask the very important question where do I cut because where exactly is the blood clot uh the blood clot can be in any position of the veins so how do we know where the blood clot is located because you don't want the surgeon to cut every single point looking for the blood clot that's going to waste a lot of time so one way in finding out the location of the blood clot is we have to understand something interesting here blood clots are caused by the protein known as fibrin so what we can do is we can actually produce monoclonal antibodies that are complementary to the fibrine protein as an example I'm showing you over there and once we have actually produced the monoclonal antibodies which are complementary to fibrin what we can do is we can actually attach radioactive material to the monoclonal antibody now what exactly is a radioactive material a radioactive material long story short is just something that gives out radiation whenever something gives out radiation you are able to detect it using special types of cameras that's as simple as that okay so as you can see the monoclonal antibody I have attached some radioactive material and they're giving out radiation in the yellow color radiation over there so what they do then is the monoclonal antibodies are then injected into the patient and it will travel in the person's blood vessels and what happens here is in the person's body look at what the monoclonal antibody does the monoclonal antibodies will bind to the blood clot why does it bind to the blood clot again because these antibodies are complementary to fibrin so logically they will actually attach to the fibrine proteins which are those green color proteins over that surrounding the red blood cells so once they attach to the blood clots the radiation because there's a very high concentration of radioactive material it would it will just give out radiation and when it gives out radiation the doctors will use a special type of camera called the gamma ray camera and when they take a picture of the person's leg using the special camera they find out that that special spot over there is yellow in color or it is glowing so why is that spot glowing by the way that spot is glowing because that's where the clot is located so the surgeons will immediately know that the blood clot is located exactly there that's where they have to cut the patient and remove the blood clot from the veins so in the exam you just have to say that monoclonal antibodies can be used to bind to blood clots all right in order to detect the location of the blood clot in a person's body this is an example of diagnosis where we are identifying and detecting the location of the disease another application of monoclonal antibodies in diagnosis is by using the monoclonal antibodies to detect and locate cancer cells in the person's body now you don't need to memorize this part but I'm showing this to you here where normal cells will have very few receptors you don't need to know the names of The receptors by the way okay and in a cancer cell they also have the receptor but the receptor is in a large concentration on the cell surface membrane so what we do here is we produce Maps which are complementary to those specific receptors and we attach radioactive material to the maps just like we did in the blood clot example so in this case here the monoclonal antibodies will then be injected into the patient right now let's take two patients over here I have patient a and patient B both of them come to the hospital and both of them are suspected to have cancer all right so the doctors will inject them with monoclonal antibodies and the monoclonal antibodies will travel in the blood in search of the cancer cells because they want to bind to The receptors on the cancer cell as you can see here by using the gamma ray camera all right person a does not show any results whatsoever but person B under the gamma ray camera they have certain parts which are glowing in yellow now why are those parts glowing in yellow because those parts which are those parts which are glowing actually have cancer cells and the MS have bound to the cancer cells have attached to the receptors on the cancer cells and they giving out the radiation in this case so the monoclonal antibody in this case is not just confirming that person B has cancer cells it is also telling us where is the location of the cancer cell and more importantly the size of the tumor because by knowing the location of the cancer cells and the size of the tumor the doctors would be better prepared to give the patients advice in what's the possible treatment uh does the patient have to go for chemotherapy or surgery or if it's untreatable so for person a however the reason why it's not glowing is because the monoclonal antibodies did not attach to any cancer cells therefore the glow is not there at all now some students will say but couldn't it bind to the normal cells as well you see the concentration of monoclonal antibody that binds to the normal cell will be very low so it will not give out a very strong glow or a fluoresence so in that case it is not detected by the gamma ray camera so in person B however the areas where it's glowing in yellow tells us that there's a lot of cancer cells in the area and a lot of the MS have actually attached to the receptors so this is extremely specific in locating the cancer cells this is another form of diagnosis because we are able to identify that the person has cancer and also detect the location of the cancer cells in the person's body and last but not least we will also be able to use monoclonal antibodies in treatment so if a person is sick how can we use monoclonal antibodies to cure them or help them solve the problem of the disease not only could we use monoclonal antibodies to detect cancer we can also use it to treat cancer now you don't have to memorize this part but traditional cancer therapy treatment involves a type of chemical called chemotherapy all right now as you can see here the purple color cells are healthy cells and the green color cells are cancer cells when you use chemotherapy drugs on the Pati the problem here is it doesn't just destroy the cancer cells it will also destroy the healthy cells as well and that's not necessarily a good thing that is why traditional ways of treating cancer can be quite difficult on the person because it damages healthy cells in the process now with new research coming up we can use monoclonal antibodies to only target the cancer cells how remember I told you that healthy cells have less of these specific receptors but cancer cells have more of these receptors so we produce the monoclonal antibodies which are specific to The receptors and what do these antibodies do these antibodies will bind to those receptors and here's the interesting thing about the monoclonal antibodies once they bind to The receptors on the cell they will signal our immune cells to destroy the cells that have lots of monoclonal antibodies on it now this is an example of an immune cell it might be a killery lymphocytic body attached to it the immune cell might go yeah that's uh that's not a problem so I'm just going to ignore that cell over that but the moment it sees the cancer cells look at the cancer cells the cancer cells have a lot of monoclonal antibodies on it this will stimulate the immune cells to go into a frenzy and only kill off the cancer cells this is a good thing right here another way that we can use monoclonal antibodies to treat cancer is instead of of attaching the radioactive material to the monoclonal antibody we will attach drugs to it and these drugs have anti-cancer properties which means to say it can kill cancer cells so when the monoclonal antibody attaches to The receptors on the cancer cells the drugs can directly be delivered into the cancer cells to destroy them so only the cancer cells are destroyed in this casee now you might be thinking but then again that monocon antibody is attaching to a normal cell as I'm circling over there but the concentration of the drug is insufficient to kill the cell when the concentration of the drugs going into the cell is very high which I'm circling there only those cancer cells which are green in color will die this is referred to as targeted therapy because in targeted therapy only the cancer cells are destroyed and the healthy cells are left undamaged so this is good another way that we can use monoclonal antibody is we can use it to treat infectious diseases obviously so as an example I'm just showing this to you here you do not need to memorize this example but I'm just I just want you to understand this now in some cases dogs may have a certain virus called the rabies virus and in the rabes virus over here this virus will cause the dogs to be extremely Wild and they tend to bite people now the rabies virus which I'm just drawing out in green it has antigens on its surface if the dog with rabies bites us the rabies virus will enter the human and sadly there is no cure for it usually people who are infected with rabis will eventually die our body cannot produce the antibodies as quickly enough to combat the rabes virus okay so we cannot use active immunity to deal with this virus by the way so is there a way to actually help treat the person with rabus in this case here we extract the antigens which are from the virus we inject it into the mouse the mouse produces plasma cells the plasma cells are extracted and fused with cancer cells and we get the hybridoma cell and once we get the proper hybrid once we get the correct hybridoma cell we make the cell undergo cell division to produce monoclonal antibodies and look at the shape of the antibodies they are complementary to the rabies virus so what we can do here is we can take that antibodies that are produced from the hybridoma cells and bottle it up and what we have over here is we have Maps or monoclonal antibodies that can combat the rabies virus so imagine if a person was bitten by a dog which has rabus the virus has now entered the person correct immediate mediately the person can go to the hospital and the monoclonal antibodies are immediately injected into the person where if the maps are given to the person the maps can directly attach to the antigens of the virus and in this case it can deactivate the pathogen now I want you to understand that we are not 100% successful yet in treating rabies using monoclonal antibodies but the research is getting better and there is a higher success rate in people who are infected with rabies so we can use the monoclonal antibodies through artificial passive immunity why is it passive immunity because the person did not produce the antibodies by themselves the person were given the antibodies and the reason why it's artificial is because the antibodies will produced through the hybridoma cells artificially the this is not a natural production of antibodies so long story short in the exam the users of monoclonal antibodies for diagnosis is to detect the blood clots in order to find out the locations of it we can also use monoclonal antibodies in the diagnosis of cancer cells where we can detect the location and the size of the tumor we can also use monoclonal antibodies in treatment where we we give monoclonal antibodies that will attach only to cancer cells to destroy specifically cancer cells and not the healthy cells in the human body this is called targeted therapy and we can also use monoclonal antibodies to treat a variety of infectious diseases I'm just using rabies as an example but we can also use monoclonal antibodies to treat covid okay so and this is a form of artificial passive immunity that's what we have to know for monoclonal antibodies for the exam I hope you understand this