all right wrapping up our discussion of uh issues with the immune system we're going to talk about autoimmunity which is a breakdown in differentiating self from non-self um we'll talk about a few ways this can happen and some of the diseases that are caused by this and then we will talk briefly about what happens when someone rejects a transplant like an organ transplant or something like that okay so let's review right self-tolerance to do this B cells and T cells have to learn not to react with self-antigens we talked about T Cell education if they react with self they get deleted in the thymus B cells undergo a similar process in the bone marrow uh if something causes a loss of self-tolerance and autoimmune disorder develops Auto means self and this means self-immune disease this can result in tissue damage there are some infections that can actually trigger autoimmune reactions um there is one example of uh s pyogens it makes a protein called the M protein that looks a lot like a heart protein that we make so the immune system reacts to this and starts making an antibody that will attack this cardiac protein and can cause rheumatic fever which has heart issues associated with it there are various ways this can happen one is spontaneous through mutation uh here is a self protein right it has two different epitopes um one of them is this kind of wedge-shaped thing and one is a circle if there's a mutation and our self-epitope changes to a square our body will not have been trained to recognize that itself right when our T cells were educated this was not a self-epitope so if there are mutations in our cells that change the antigens uh we can then actually lead to T cells being activated against them and autoimmune disorders happening this is kind of like the case I just talked about with the bacteria that makes something that looks kind of like our antigen this is a similar process but here our own genome has mutated and caused something that looks slightly similar but uh causes an immune reaction and then it attacks our body so let's look at a case study here we have Tamil she's 26 years old and she recently just started developing joint pain in her fingers wrists ankles and she noticed this strange rash that goes through her cheeks over her nose and it kind of looks like a butterfly so she goes to the physician and this redness has grown worse um particularly after she was out in the sun for a very short time so it you know she thought it might be a sunburn but such a short time in the in the sun seems strange so they do a blood test and um she's showing normal blood cells but her serum anti-nuclear antibody test is very positive um it's a very high level um so this is looking at basically antibodies that attack the body anti-nucleus antibodies so she has a lot of antibodies that are attacking her own body the tighter level is down to one to 256 so remember back to that Elisa this is a very high level normal levels are negative at one to eight dilution so she has very high levels of these self antibodies basically well based on the lab findings the physician says that she has systemic lupus erythromatosis which is a common autoimmune disorder complexes of these Auto antibodies form between her own proteins and the nuclear material like DNA and histones and things like this that are all in the nucleus and these antigen antibody complexes form and then travel to various tissues and Trigger inflammation think back to the type 3 hypersensitivity this is similar to that it's a type of it so this is going out into the joints as we talked about it's also going to the kidneys and various organs so if you were a fan of the show House you will notice that they always guess that it's lupus but as you know Dr House always says it's never lupus they choose lupus so often because we don't really know what causes this in a lot of cases um we don't understand why this process develops and uh it's a great thing for a TV show because you can kind of guess that it's lupus all the time because uh there's no great cause for it so but as we know it's never lupus right unless I think there's like one episode when it's probably lupus right there are other autoimmune diseases um again Auto antibodies binding to different parts of the body Graves disease and Hashimoto's disease both autoimmune um diseases that involve the thyroid in Graves disease Auto antibodies bind to the thyroid stimulating hormone receptor and they actually cause hyperthyroidism so basically that the thyroid is over activated this leads to a very high metabolic rate high energy levels in the patient in Hashimoto's disease it's the opposite the auto antibodies bind and damage the thyroid which causes hypothyroidism low thyroidism which causes severe fatigue from this um so these are both thyroid autoimmune diseases myasthenia gravis um Auto antibodies bind and block muscle receptors for acetylcholine this leads to muscle weakness you'll see a drooping eyelid here and it will eventually progress to more muscle um weakness this is a type 2 hypersensitivity because it's binding to a cell surface protein Diabetes Type 1 diabetes can be an autoimmune disorder where T cells start attacking the pancreas cells and leads to no insulin production so this is kind of a Type 4 hypersensitivity basically autoimmune disorder it destroys the pancreas cells that can make insulin so type 1 is childhood onset and it can be caused by this autoimmune disorder rheumatoid arthritis also an autoimmune disorder antibodies form those immune complexes in the connective tissue of joints and cause inflammation so here's a normal joint because of these complexes of antibodies it starts forming inflammation here and actually later can call in T cells and lead to more damage on this can lead to prolonged inflammation so one of the treatments is uh anti-inflammatory drugs long term you have to go to Stronger things that basically kind of suppress the immune system this is actually very common particularly in females it's estimated about one in a hundred will develop rheumatoid arthritis so you probably know someone that has this and uh you can see how kind of debilitating it can be there's many other autoimmune disorders this is just a few I want to finish with talking about organ transplantation and organ donation so I we've talked about the immune system recognizing self versus non-self this also goes not just between different species but between different individuals um our immune system recognizes MHC and it recognizes self versus non-self MHC so when you get an organ transplant we have to make sure that the MHC molecules are compatible with your own if not your body is going to bind to and reject this as foreign material and will actually start destroying it the CDA T cells will come in and start destroying it so this is why we often look for close relatives that are genetic matches for donations um interestingly you might say well why doesn't this happen with red blood cells well red blood cells have no nucleus so they have no MHC on them so that's why you can get blood of the same type from any individual on the planet right we don't have to match MHC for blood otherwise blood donation would be basically impossible that would be very devastating right there is an interesting problem that can happen though sometimes the the grafted material the the donated organ can bring immune cells with it and those immune cells can actually attack the new host we call this graph versus host disease um so it is really important that there are matches here and even when they match things can go wrong um in a lot of cases we still need to suppress the immune system when a organ transplant is done to keep our body basically from attacking the new material as foreign so we have to take basically immune system inhibitor drugs to do this okay we're at the end uh I think there's a lot of really cool material in there hopefully you learned something hopefully something piqued your interest in there that is it for the material that we're covering for this unit I'm in the final unit we will finish up with a few various different things a little bit about how pathogens cause disease how we detect microbes and some tests and things and then talking about epidemiology all right that's it see you later