How do monoclonal antibodies work? Rituximab, infliximab, adalimumab and others

hi this is tom from zero define is calm in this video i want to talk about monoclonal antibodies I want to talk about them firstly because they're more and more monoclonal antibody treatments that are coming out all the time and it will be important for you to understand how they work but also because they're really cool and exciting treatment with lots of potential to revolutionize some of the treatments of the worst conditions to understand how monoclonal antibodies work firstly we need a bit of background knowledge of immunology and if you want to learn more about the immune system I recommend watching the zeroD finals video on the cells of the immune system and the immune system in one video but for this video we're going to focus on the most relevant part and we need to focus mainly on the b-cells and the antibodies these cells are a very important part of the specific immune system b-cells have antibodies on their surface membrane and each b-cell has antibodies that are specific to a single antigen and they useless against all other antigens so for example if you choose one b-cell at random from within a lymph node it may have antibodies that are only useful to a very specific antigen that's found on a specific bacteria that only exists in some remote part of the world or it may have an antigen that's completely useless altogether that specific b-cell will never encounter that antigen so it's never going to be able to contribute to the immune response you might choose a b-cell that has an antibody that's specific to an antigen on a virus that's caused by the common cold and when the person picks up that specific virus the b-cell multiplies furiously and becomes essential to the immune response to fighting off that infection with that virus and protecting against that virus in the future once a b-cell encounters the antigen that matches its antibody it becomes activated and undergoes differentiation and becomes either a plasma cell or a memory B cell plasma cells produce vast amounts of their specific antibody and memory b-cells hang around for years as part of the immune memory so that if they're needed again they can be quickly activated so let's talk about antibodies antibodies are also known as immunoglobulins so you might hear either of these phrases and antibodies are complex molecules that are made up of two heavy chains and two light chains that arranged in a Y shape the bottom of the Y contains something called the FC portion and this remains the same amongst all antibodies and this is the portion that's used for binding to the cells of the immune system so that they can recognize the antibody and carry out their function the cells of the immune system have an FC receptor that binds to the FC portion of the antibody the top of the Y contains what's called the variable region and this has millions of possible configurations and it's this part that's designed to match only a single type of antigen so how these antibodies any use in fighting off disease antibodies help the immune response in a variety of different ways as we go through these different ways we're going to talk about pathogens but instead of pathogens we can also mean cancer cells or cells of the person's own body when they have got an autoimmune condition remember antigens are just proteins and they don't necessarily have to be from pathogens they can be proteins from anywhere firstly antibodies attach themselves to the antigen and become something called an antibody antigen complex and this antigen antibody complexes activate the classical pathway of the complement system which in turn leads to the destruction of pathogens secondly antibodies can attach themselves to the toxins produced by pathogens which themselves are antigens and they neutralize the effects of these toxins thirdly antibodies can attach themselves to the receptors on pathogens and disrupt the function of that receptor so for example it could stop viruses from being able to recognize the cells that it wants to invade and therefore prevent viral invasion or it could bind to receptors in a bacterial cell wall that are important for that cell taking in essential nutrients and therefore starving the bacteria of those nutrients and reducing its pathogenicity or flee antibodies can attach themselves to pathogens and then clump together to slow the spread of pathogens down and this is called agglutination the fifth thing they can do is antibodies can act as ops onehans and this involves attaching themselves to pathogens and making it easier for Faga sites to recognize and destroy those pathogens that would have otherwise not been able to recognize them because of the primitive measure that's usually used by macrophages and neutrophils for recognizing pathogens so they help these cells of the immune system the FEA sites to recognize the pathogens and the sick thing is antibody dependent cell-mediated cytotoxicity and this is where the antibodies attach themselves to pathogens or abnormal cells and then they help natural killer cells neutrophils macrophages or a sinner fills to recognize the pathogen and kill it so finally let's get on to monoclonal antibodies so we know that we have these antibodies which are part of the immune system and provide a really effective way of fighting off pathogens and essentially they're very good at selectively identifying specific proteins that are part of a harmful process such as toxins or parts of bacteria or parts of cancer cells and set the immune system to work destroying whatever is associated with that antigen so when treating it's possible to identify proteins or antigens that are associated with harmful processes that we'd like to stop so for example you might know that a patient with breast cancer has the her2 receptor protein on the surface of their breast cancer cells and these scenarios it would be good to have a medication that killed cells associated with that protein and that's where monoclonal antibodies come in monoclonal antibodies which basically means single clones are a single type of antibody that target a specific protein and there's loads of different monoclonal antibodies that target different proteins however each monoclonal antibody has its own specific target protein and we can develop these monoclonal antibodies in a lab and then inject them into patients once we inject them the antibodies then travel to their target and activate the immune system and attack that target in the same way that the antibodies produced by a person's own b-cells would do in this way the monoclonal antibodies essentially utilized that the patient's own immune system in a targeted way that's useful for their particular condition so let's go through some examples of monoclonal antibodies first we will start with rituximab and this is a monoclonal antibody that targets the cd20 protein on the surface of b-cells and it's used for immuno suppression for autoimmune conditions and cancers related to the b-cells so it's used in conditions like non-hodgkins lymphoma rheumatoid arthritis and autoimmune hemolytic anemia and it causes the immune system to target those B cells that are associated with that cd20 protein and reduces the function of those cells next let's talk about alum to zoom up and this is a monoclonal antibody that targets the CD 52 protein on T and B lymphocytes and it's used to treat multiple sclerosis and certain types of leukemia and it works by targeting those T and B cells that are associated with that CD 52 protein and the intention is to reduce the amount of those cells that might be targeting the myelin sheath in ms or may be cancerous in leukemia another example is trust toss zoo map and this is a monoclonal antibody that targets their her2 receptor protein so like we talked about that patient with breast cancer that's known to be her2 positive we can give trastuzumab which then targets that her2 receptor protein and causes the immune system to attack cells associated with that protein example is adalimumab and infliximab and these are both monoclonal antibodies that target a cytokine called tumor necrosis factor-alpha and tumor necrosis factor alpha is involved in generating inflammation as part of an acute phase reaction and this is an important cytokine that's involved in a lot of inflammatory processes in conditions like inflammatory bowel disease rheumatoid arthritis and psoriasis so these monoclonal antibodies that attack this cytokine reduce the inflammatory response in these conditions and can be very effective in treating them common monoclonal antibody that you might come across ran a busy map and this targets vascular endothelial growth factor a or veg F a which is a growth factor that stimulates the development of new blood vessels is injected directly into the eye of patients with wet age-related macular degeneration and it targets that veg earth growth factor and destroys it and this helps to slow the development of new blood vessels in the retina of patients with wet age-related macular degeneration and slow the progression of the disease so thanks for watching I hope you found this video helpful if you did don't forget there's plenty of other resources on the zero to finals website including loads and loads of notes on various different topics that you might cover in medical school with specially made illustrations there's also a whole test section where you can find loads of questions to test your knowledge and see where you're up to in preparation for your exams there's also a blog where I share a lot of my ideas about a career in medicine and tips on how to have success as a doctor and if you want to help me out on YouTube you can always leave me a thumbs up give me a comment or even subscribe to the channel so that you can find out when the next videos are coming out so I'll see you again soon

Channel: Zero To Finals

Views: 319,702

Rating: 4.960587 out of 5

Keywords: education, medicine, rituximab, infliximab, adalimumab, trastuzumab, ranibizumab, doctor, pharmacology, immunology, herceptin, humira

Id: h6sGMaf6Yew

Length: 11min 49sec (709 seconds)

Published: Sun Feb 10 2019