Transplantation and Immune Pharmocotherapy Part 1 PDF

All right, so it's nice to meet all of these faces again. I do need to email a list of students that I got today because I've written down on a shirt with all of the different attendance from Friday. I hope you guys enjoyed it. I'm sorry you weren't able to come and creepily walk by and just look at...

All right, so it's nice to meet all of these faces again. I do need to email a list of students that I got today because I've written down on a shirt with all of the different attendance from Friday. I hope you guys enjoyed it. I'm sorry you weren't able to come and creepily walk by and just look at posters and idols and see if you can even realize this. You could be like, hmm, come on, I want to talk to you, which is silly, but you guys are participating anyway. There's a lot of really interesting research here at the Marian. Done! The other thing is, I don't want to talk to any of the groups, but they're like, yeah, this is my idea. Students are allowed to come up with their own projects. They've had a faculty member who's adjacent enough to work with you. And so there are a couple projects like Reesha's oral presentation on that as a city with medical students was an idea she was curious about. She proposed one of our faculty members to lead that research. So you're not going to do my ideas or any of the other faculty ideas. You have ideas that are within the realm of reason there are faculty members here who are willing to work with you and help get your projects off the ground. So last recording we left off talking about different HIV proteins. You will unfortunately have to learn all of them next semester. So thankfully not right now. For right now, just because it is relevant for diagnostics, we expect you to know differences between HIV1 and HIV2. There are different subtypes of HIV. HIV1 is more prevalent. And so they do different terms of protein expression. HIV1 is BPU, but you don't see that orange square on HIV2. Instead, they have VPX with HIV2. HIV1 and 2 do slightly respond to treatments differently. So this is diagonally important, especially with immunology, because you guys need to be in a lab. How do we determine for patients with HIV1 and HIV2 what would we need to do a test for in order to be able to properly guide them on the street? That's why it's irrelevant. Here's two. The other one that I think is useful to know now, just start introducing you to our gag poll. And the very well-named is Envelope protein. It's for the viral spike envelope. GP120 and N41. The protein is also known as a co-operative CD4. So it also explains why HIV is able to come back to certain subjects specifically to you before which I've done a museum here, too. Yeah, I just think it's the core structure of HIV, which you'll see on a couple different slides. It's just the inner portions of it. And polar enzymes, like reverse transcriptase, protease, integrase, which helps HIV go backwards. You'll learn a lot more in the next semester. HIV is an oddball. It is an RNA virus. And the normal central dogma of molecular biology is you have RNA where does it go? HIV goes backwards. HIV incorporates into a patient's DNA, which is why it is something you have for the rest of your life, and why it is a secondary immuno-dish disease disorder. It has reverse transcriptase enzyme, which, like a sound, it reverses transcription. It takes DNA RNA and makes it DNA and incorporates it into your genome. And so HIV for the rest of your life, especially here, that envelope protein, which helps it is the receptor binding on the CD4 specifically targets CD4 T cells. It infects it, damages it, the whole function of those cells, and when you eventually destroy and deplete them, if you take out the general DNA, what do you think is going to happen? Just an absolute chaos. So that's basically what AIDS is. AIDS is a progression of HIV infections to the point that your CD4 levels are below a threshold needed to be able to fight habits. So patients living with HIV and AIDS typically don't die from the virus themselves. It's considered a secondary consequence, like primary source of. They're usually dying from fungal infections, or percoccus and other fungal infections. They can lead to yeast infections, things like that. Other bacterial infections like tuberculosis. It's not HIV that kills it. HIV destroys the T cells. They don't have genitals in the army. They can't help successful immune responses to everything else. And they end up dying because they're more susceptible to other infections, unfortunately. So it is important that here, this is just showing you how the virus enters. It needs to bind onto a receptor, and it coerces its main receptor here, CD4. And then it uses a CCR5 receptor. Unfortunately, CCR5 is also found on macrophage monocytes. They also do know that HIV is capable of binding on an infecting. What happens is the virus binds on and injects it into the bacterial inside. There's really cool facts here. There are some patients who are deficient in the protein receptor, CCR5, needed in order for HIV to also bind on an infective cell. And so there are patients whose immune systems actually gave them an advantage, even though they're depleting a receptor that helps us be more functioning here. And so there are patients whose CCR5 is more than a delta-thirty mutation. If you have one copy of it, they said you could be like a six-ton chance of your exposure, and you won't contract it. If you have both copies, you could be strangled with a pediatric virus and not contract the virus, which is wild to think about. But this is one example where the immune system is a little altered, but in a good way. It provides resistance to certain infections. They've also tracked them down. It's mostly in populations of Western European descent, whose families have been tracked back to the black plague. Black plague is a bacterial infection, but they think that some reason this patient may have provided some sort of survival mechanism for the black plague. Therefore, those answers divide past that down, and now it actually provides some protection against HIV, which is pretty cool to think about overall. Don't panic. This is big picture stuff. This isn't a life cycle HIV. This is a lot more next semester when we go through HIV, like we get another electron A to get a lot more focus on this. If you're not familiar with this, it's a nice introduction to how this works out. HIV has a weird word that goes backwards. It is informal, so usually when you have a viral infection, it has to be under receptors and co- receptors of the cells. It's going to affect COVID, like A2 and T and PRS2. Every virus is a different receptor than it likes. It's a different receptor from different cell types. So it affects which cell types can be infected by various viruses in T2. But then it allows that the fusion of the enliloped virus allows the fusion of the enliloped today that will fossil a biolayer membrane with R. So basically the viral membrane fuses with R and injects the genetic material inside here. Then at this point, the virus has come with its own enzymes, but this is a specifically reversed transcriptase to convert since our body can't read already backwards. It has to come with its own transcriptase to create this viral cDNA or copyDNA. Here, the body recognizes that you have this extra DNA outside of the nucleus where it doesn't belong. Unfortunately, your very helpful body should transport that DNA into the nucleus because it's like, oh, you must be a little buddy, let's put you back where you belong. Oops. And so it incorporates into our DNA here, so when our body goes through and transcribes the DNA to RNA, it's actually incorporating in those pieces of genetic material from HIV. And then once the RNA is out in the cytoplasm, the body reads it in the normal process again, makes those proteins, and then in the cytoplasm here, the body starts rehacking all of those pieces together, and then the virus buds out from the cell membrane and goes on to infect more cells. So in terms of viruses, HIV is brilliant, sneaky, and horrific in that it will subvert a lot of mechanisms of our immune system here. So I wonder the broad overview of this. You might see in order to step this question, but that way I can test you guys without being too overwhelming with a lot of material here. Just pace yourself through it. It's logical, it makes sense. Just go through it slowly. It'll be fine. So after infection HIV, so when you first infected, you do see symptoms very briefly. You do see infections very briefly because there's a short dip in CD4 T cells right after infection, but the body mounts a response to it, tries to control the HIV, surprises it a little bit, and we're able to see rebounds in that CD4 T cell count. And for the most part, patients have this asymptomatic period where viruses are hiding outside the body, sometimes it's replicating, sometimes it's not, and this could be either an antiretroviral therapy, obviously if you have antiretroviral therapy, it's blocking virus from spreading, or replicating, there's multiple different types of therapy, and that can extend the period of time in which you are asymptomatic, because it decreases that viral load overall, but very early on you do see this flu-like symptoms as it's taking out your CD4 T cells, your immune system's fighting back, but then you have a seroconversion where you control the infection, your CD4 T cells will go back to normal, but then over the rest of your life it's going to be a gradual decline. And for the most part, we gather that you have less than 500 per microliter number CD4 T cell count. That's when we say your asymptomatic phase starts to experience more symptoms associated in HIV, so flu-like the most part is viral infection in your body. It's really seen in your area, your macrophages are aggregated, things like that, and then eventually when you drop a load 200 is when you are officially defined as having AIDS, and if your T cell levels are low, a threshold where you are at this point, it's acquired in the infectious viewer at a point where your immune system can't function against anything else, and at that point you are in critical periods and very frequently patients die very soon after that if it is not managed. And so that leads me into, well this first, and then we'll talk about some of the research I did. But it's showing very early on our immune response to HIV, that is showing the infectious plasma, here's showing the antibodies against poor proteins, we also have antibodies against the envelope, because again there are a lot of different adenoclinic proteins with viruses that our bodies can make immune responses here too. We can also make HIV specific biotoxic T cells as our immune system ramps up. So we can get that first infection again, you know the virus increases and infects a lot of cells, causes damage to flu-like symptoms, but our immune system at the same time is ramping up responses, we're triggering that adapt immune response and eventually gets it under control, and that's what leads to that sero-conversion, where we have very very low levels, if at all, in our body, you have a little bit of repeats, and this is usually when you've got cold, menstruation, stressful events, things like that. In some cases your immune system is as simple as this, you have minor little peaks and viruses here and there, but for the most part pretty well contained by these immune responses here too, but eventually HIV starts to ramp up production, you're not entirely sure why more than likely just age as you're getting older, you're not having any pollution, you're in your T cells, HIV is taking advantage of the fact that you have your T cells causing more damage, and then you start to have that symptomatic period within two to three years, which is when it's very critical to have patients come in pretty frequently for testing, and adjusting antiretroviral therapy as possible as necessary. It is also possible to see patients develop resistance to different antiretroviral drugs, which is why we are now prescribing the combination of typically two or more, like the gold standard right now is three different types of meds, that if you just throw everything in the virus that you keep it down enough, that hopefully it doesn't develop resistance to all three of them, and then once you progress to that age criteria, your life rate is typically less than a year at that point, unless you can get it back under control, which you get as this heavy antiretroviral therapy and stuff like that. So at least in my research, because obviously if you drop a certain threshold and there's imminent death in the next year, something needs to be done. And so what we're looking at too is because we know CR5 is also found on monocytes, so it means in theory, HIV also infects monocytes, and we have data to support this, we also find it in the macrophages. We try to see, are there actually changes in monocyte turnover? Monocyte turnover means bodies producing more monocytes to make up the fact that suddenly they're dying or something's wrong with them. They're getting infected, they're getting damaged, you realize that, and we actually started increasing production of monocyte turnover. The lab that I was in actually showed monocyte turnover increases a couple of months before you see the drop-off from seeking 14 cell levels to the criteria of the finished rate. And it's been pretty consistent in both primary and human studies. It is not currently acceptable practice, which is why it's not relevant to your exam, but it's your future as a health care provider. We want the best for our patients. This is something that we're going to speak out. If you've seen these monocytes growing up, it might be time to start looking at their antiretroviral therapy. I mean, changes need to be made because they're kind of potentially progressing to A's into the monocytes turnover. If you're curious about how it works again, not on the exam, this is the paper with the controversial data that published that changed the paradigm of the field. The lab that I was in showed that what they think is happening is monocytes become macrophages. If they're infected, the macrophages are going to be damaged. They're not going to be functioning well. Your body is constantly producing new monocytes to create more macrophages to replace these infected macrophages that are not doing their jobs well. And that's why we have rapid increase in monocyte turnover and monocyte production because our body is trying to fight back again because the virus is slowly ramping up and increasing. So it might be an earlier time when to do more aggressive therapies to get a patient in a better state before they potentially progress to A's. So that's why I share it because I think it's important as you guys will treat A's with HIV with the rate of the HIV infection in the United States. It's only a matter of time, so it is important to know that here. HIV is particularly sneaky. It was just immune responses. It means there's two antiretroviral drugs through rapid mutation too. There are a lot of different strains too in HIV-1 and HIV-2 subtypes here. This one is just showing you the data. So it's just supporting information for the fact that we do know that it develops resistance to proteins and inhibitor drugs. So blocking one of the proteins needed in its life cycle here. But antiretroviral therapy does reduce blood-borne HIV detector levels. I'm pretty sure we've all heard of Magic Johnson, basketball fans. He has undetectable HIV which means you don't see virus in his blood. It's a good thing. It means not to actively replicate virus in his blood, but probably moderately controlled infections. Antiretroviral therapy is still very, very useful because it is showing you that we will find it below the level of detection to a very, very small amount actually. Viral antiretroviral plasma is like 10. I'm not sure the units on that one, but a very, very small amount. So if you have any level of viral replication below that, it's considered below the level of detection. At this point, you're not considered infectious. And so that's why it's very important for patients to also stay on top of their drugs. It keeps the virus in check. However, we do see an increase in drug resistance in the plasma overall. So we will take that out, sample it, and see what kind of traits these other viruses have picked up. And I think several weeks after the start of a protease inhibitor, which is why again we're using that combination drug with two or more, again, preferably three. Just because if you throw everything at it and block multiple aspects of its life cycle, it's going to make it harder if you chop up an arm. Well, eventually you learn how to use a left arm. Or if you chop off both arms and legs, it can be really hard to learn how to use pain, which is just one. So that's kind of the strategy behind using local drugs to control it. They do still work. It's just a longer and better period of time when they do work to use more. That's the standard of practice you guys are going to use, too. Because antiretroviral drugs do rapidly clear the virus from the blood, and therefore have increased the number of CD4 T-cells if they're not being attacked or not being damaged, they can live healthy normal lives. And so, their infection is CD4 T-cells count more than 99% of the plasma that's in blood, because then T-cells are most circulating from the blood, and some of them avoid tissue, too. And so the infected cells can be short-lived, so we see them drop off. And so if we block viral production with different types of drug, it helps then their virus eventually get filtered out, your immune system will be able to take control of the source and keep it under check. That's why, again, we use multiple types of drugs to keep it in place. That gives it time for more T-cells to be produced and created, thus controlling the infection and keeping it in check, also maintaining your CD4 T-cells, so that you don't progress to the age of the goal here. We do something bolded. It's a definition known as clinical latency, and it defines the period of active infection and renewal of CD4 T-cells. Which means, the virus is still present within your body, however your body is producing enough CD4 T-cells to not really experience these symptoms. And so it's clinical because you still have a virus within the rest of your life, but you're producing enough CD4 T-cells to keep it in check. And so it's kind of that period where we're looking at it as that. Zero conversion, plateau control is usually considered clinical latency because you still have virus, everyone's probably a little peaked in it where it is still producing more viruses, but the drugs help you to check enough for your immune system to keep it in control, also your immune system can do a decent job by itself, but you have a shorter quality of life, or shorter life span in a shorter or worse quality of life if you're not doing anti-retro drugs. Do not have neurodegenerative problems, although you'll learn... Actually, nearly everything will be in the next semester. So, something to look forward to. These are all the different patterns that we frequently see in patients with AIDS. Because, again, your CD4 T-cell counts. Because of that, it's wiping out all possible responses. So you frequently see patients die from parasites, bacteria infections, specifically tuberculosis. It's very, very common. Salmonella. A foodborne. A lot of times you can take patients out too. Fungi. We frequently seeococcus. And patients living with HIV. As well as other viruses too. And unfortunately, we see cancers associated with it too. And so a minority of HIV-infected individuals make antibodies that neutralize mini-strangivitis. We did find that there would be super......are superior to most antibodies than anybody else exposed HIV-buses. And you guys are known as broadly neutralized antibodies. That really had a question. One of the wrong answer choices was B-A-N-A-S. Because... I'm looking for B-A-S. But broadly neutralizing A-B-S antibodies. And so we did find that patients, they perceived these beautiful antibodies that really died back in infection. And so when they identified these, they were able to actually fill them out from patients' plasma. And actually isolate them to create various treatments. And help control the antibody treatment. And help control others with HIV. The whole thing about these is it actually recognizes four different sort of epitopes of the like protein. But it's a really nice antibody. And it's affecting and recognizing multiple parts of the virus here. So this is showing you that it's binding onto multiple parts of the fragment here. I wouldn't remember all the different pieces of it. But with the broadly neutralized antibodies are very effective. They were isolated from patients who just mount really nice immune responses to it. And they've been used as a potential treatment option to also help control it. If we can make synthetic antibodies or even isolate it through things like that. To help control infection even more. So this is one more level that we can fight back with overall. So that is the A-B question. Do we have any questions about that one? Do we have a little bit of time to kind of... Time for Jack? I did make it. We haven't seen next week. Next week I did have... Nope, it's this week. It's this week. It's this week. Next week we'll be giving in Monday's type sensitivity reporting. So this week we've got our instruction. This is like transplantation. And then it's like transplantation slash intrinsic cancer slash cancer. Because there's only two power points in this week. We're just trying to catch up on all the material. They're all just slightly longer power points. You look for a third power point. There is none. It does stay on our hands. Of course, it's just two of them. But together we caught up. So we should be good Friday. I've been in the type sensitivity lecture. Dr. Nate Lam, who's an in the studio. He's a TNC now. He got his first choice. He was a DMS grad. Probably phenomenal computer. You guys will love him a lot more than me. He can be like, talk slowly. He timed it really well. He practiced a lot. He timed it really well. It's beautiful. One of the best presidents in the world. I was like, oh, this is so exciting. That guy's going to do it. Tell me more. You guys will love it. It's fantastic. And now we will start introducing some of the transplantation. Whatever we don't finish today, obviously. We'll go over to Wednesday. And if they have extra time on Wednesday, then we will put up cancer. And then whatever we don't finish on Wednesday for cancer will be Friday. And then Monday Thanksgiving, I hope you guys have a good break. Oh, I shouldn't do that while you guys are here. I know Michelle is going to reach out. Where's Michelle? Michelle is not here. She's going to reach out and ask if it was OK. We've got a ton of people going to eat ham in the box. Unfortunately, obviously, the oxygen is a ham. It's smoked pork sausage. I know some people don't eat. I was already planning to make ice smoke. I'm going to go back to red beans from the world in my series. I was planning on making red beans and rice this week. So now I'm going to make red beans and rice with all of you and ham and stuff for your Thanksgiving call on Thursday. So if you'd like to see the Dr. So if you'd like to see the Dr. Lee camera down in the kitchen, RCP and the little QR code and the email I sent out this morning, I hope you guys check your email. If not, you're missing out on delicious food. I got smoked in my series and I'm pretty sure I had bags of dried meat. And it's a bottle of else. I'm pretty sure yesterday I was like, what? But anyway, it's Kinsey in here. Yes! Yes! Oh, Kinsey. Kinsey, this is much late and I'm very sorry about that. But we are going to appreciate these beautiful Halloween costumes and the effort they must take to put these good ways and girls. Yes. Oh, girls. Just girls. Good girls in these Halloween costumes here. So Poppy is a black pit formist. Poppy looks like an instigator. Poppy's trouble. Poppy's trouble. Aww. The little sister that always makes the big sister get in trouble. I was like, oh, she just hit me in the face. Poppy looks like she's doing like... She's the aggressor here. That's the best though. This is Charlotte and that's Poppy. And they're so cute and I love them. Very much. Also the Roomba. Did they ever chase the Roomba? I really want to know. Did they chase the Roomba? They don't. Like, they don't fluff it. I don't know. It's like, I see a biscuit stuck up in here. Cats are easily smart and like, we're like, let's break it. Sticking larger objects and then the Roomba will break. Very smart. And so, because they're just the dogs. Here is Moose. Moose covering his face. Is there her face? His face. And then... Unfortunately, I bet that would be pretty close. But anyway, I mentioned, this is today's lecture. Organization structure. Wednesday, Wednesday's lecture. Transplantation. Whatever we were like, how do we have it? Or start cancer. Friday, we just fell off. And then Monday's activity is Thanksgiving. It's like, pretty chill. I don't know if it's Thanksgiving yet. If you guys do this, if you look far away and it's cheaper to fly out earlier, none of us are going to care. We'd rather you guys have a good vacation with your family. We're all reasonable in that front. Thanksgiving, obviously. I will not be here. So, don't come looking for me. Audience disorders. What's wrong with me, Katie? This will be fun to be hopefully more interactive. And then the final immunology debrief. I'm trying to think if we have some sort of interesting interactive class activity that we can do. I'll probably get RSPC to see if he's going to be here for the players we need. But probably some sort of fun review to set everything. And then obviously maybe some sort of fun. Why are you here today? Hopefully you're here today. But just in case you're struggling today, we are talking about matching and transplantation today. And the chance of finding a match can actually vary based on SBC status too. Black or African American individuals, over 3 out of 4 will not find a donor in their life. Asian or Pacific Islander. Greater than 2 out of 4 will not find a donor. Hispanic or Latino. Over 2 out of 4 will not find a donor. American or Alaska Native. Less than 2 out of 4 will not find a donor. White is one of the most frequently matched. A lot more people of the way than this use sign up to do the bubble swabs to even determine. So, say that you guys are curious. You're interested. Okay, I'll help you. I'm willing to be back to my community. Being the master of self-changing, I'm going to hand out an RMP or something like that. I've got a new abbreviation for it. But you can send off married and once in a while to do blushes. But it's a bubble. You just rub your cheek, get some cheek cells and send it off. You don't have anything else after that. They scan you or your arm just try to find out if any person comes through needing a donation. Match it and they will contact you. You can still turn down the number on what the match is. But at least you can find out. You're in the system and you're there and available. It's like someone needs bone marrow. That's something where it's typically like... I'd say it's a day process. Maybe a week recovery is going to be sore. But they frequently drill into femur or long bones. Just take a little bit of your bone marrow. You're frequently in and out. It's very, very safe. It's invasive if you drive through the drilling. Drilling your bone. But it's the way that you can get back and help people over the U.S. We need transplantations of those. Bone marrow blood. Bone marrow blood. Different types of tissues. Organs too. Or organs as well. Every three minutes someone is diagonally blood cancer. Blood cancer is one all the time that ran through this morning. We've had several people diagonally blood cancer and need transfusion. That's 480 people each day by the end of this class. 180 people will be diagnosed with a blood cancer and will need bone marrow transplant. So again, you can sign off for like cognitive kits. And if you guys are interested also, we're about to get through one there. They'll provide free return shipping. Susan's like, no signal to get. Just because you do it does not mean you have to agree to then donate. Just at least put the information out there in case. And then they contact and say, hey, you know. You have a five-year-old girl who just died of leukemia. You have a very free chance of recovery. But you're the best match that we have. We need bone marrow. At that point, you set up a donation. So only one in 430 who have a reduce and then go on and actually donate. You may never actually be a match. But if your data is there, just in case someone comes through and doesn't need it, it's a possibility for you to get back. So I do recommend it overall. So talking about the science transplantation, it's actually quite thorough. There's a lot of stuff to go through because the risk of rejection is incredibly dangerous overall. And there are different types of rejection we'll talk about. Blood is actually the most commonly transplanted tissue in the United States. And actually, we'll talk about transplantation. Unfortunately, you guys didn't know Dr. Yu. But we've had an analyst. I think she took a different position about two years ago. But unfortunately, she passed away two weeks ago from a sudden brain injury. She donated on a match list and she donated all her organs to science. In the house, a lot of faculty are all listed willing to donate. They were all organ donors. It is the way that you can continue to give back and give someone else a little bit of future. We are all very happy. We are still all very grateful doctors. She was also really in the behind the kids. Pretty rough. But we do have different types of transplantation that affect the likelihood of rejection. And so they can categorize a couple of different ways. By location or genetic relationship. Oftentimes we see both terms used in a sentence. So there could be various intermixed resources to be sure to be familiar with all terms. Like Matura naive. Or we can't Matura naive. Not even activated. No, you can't Matura naive. Matura naive. There we go. So we talked about location. You have two main locations. You have orthotopic. Where tissues and organs are placed in their normal and atomic location. So like cutting your finger off. You're losing your finger. Cut your finger off. Or a heterotopic. Where the grass is placed inside of their normal. You cut the thumb off and place it in someone's ear. That is not normal. So heterotopic. Heterotopic being different. And so. Heterotopic grass can be useful. Especially when orthotopic places may be a little bit more difficult. I don't want to elaborate on that. Because I can't think of a good example at this specific moment with all you guys staring at me. That's what you should do in my donor recipient relationships. This is a little bit more complex. You have a couple different subjects in it. Autograph means self. So if you've ever heard of burn individuals. Where they have like burn off part of their face. They will cut off skin usually from the leg or bust and place it onto the face. So it's skin graft from you. But placed back into different parts of your skin. And syngeneic also known as isograft. It's transferred to be different individuals for genetically identical or nearly so. So frequently identical twins or members of an inbred strain. And so syngeneic for the most part. The likely to be inbred strain is very slim. It will mostly be inbred or not inbred. Identical twins. Alrighty. Syngeneic. Identical twins. So not for maternal twins. Identical. Because again the material is so similar. You can swap them out in between. Allogeneic graft which is shortened to aloe graft. Transfer between genetically disparate or different individuals of the same species. So brother and sister. Parent and child or even unrelated individuals who have enough compatibility matching. That you can do this transplant. You really don't want to do people who are significantly different. We also have known as isograft. And this is exchange between members of different species. Like placement of primary parts of the human recipient. We're all seen as the pig parts now too. And so I will also elaborate on my favorite time for story time. I love it. He's the coolest person I've ever met. So in the rascal we all got really weird nicknames. That's kind of what you do. It's like a cult. They give you weird nicknames. At the primary center we have a guy named Nimble Nick. All of his folders are every computer. He didn't do it. We all changed it for him. We're all labeled Nimble Nick. And this is because he's a brilliant, brilliant man. Has relatives diagnosed with breast cancer. And really when you don't dissect them a lot of times too they will take a lot of tissue. Usually they've never seen one. And at times they've gotten a lot of surgery. Just the mass of a scar. And it affects the quality of life and the self- esteem of the individual experiencing breast cancer. And it's already a really traumatic thing to experience. He wanted to try to apply quality of life back to him. Again, he could do *** needs or like a breast transplant. And things like that. After *** he's kind of replaced all of you and things like that. But it still kind of never really looks the same. This is really an idea. What if we take a lower tissue before a double mastectomy. They planted it onto primates. On the backs of primates. It actually grew human nipples on the backs of primates. And then at the end once we had full development of the tissue. And then you guys thought it was a cancerous tissue. They then cut the nipples out of the backs of the primates. And transplanted it back onto the woman with a double mastectomy. And that was kind of replacing. They made it as normal as possible given a very traumatic nature of surgery. When I was in graduate school he was just finishing up his speech on it. And he actually dropped out. And you know the act back is like he's literally made massive strides in the field. But he put up a biotech company. And they're actually using like they want their human, full human transplants of it now. Except they didn't use the stuff they did in New Orleans. We started it. And so it was a really cool thought. That he still used autographed tissue. To grow it in a different area. Or a different animal. But still considered at that point autographed. Because the tissues themselves are still from the donor. You know they needed the tissue grown. Then transplanted back. This is kind of a new revolutionary way. That you can revolutionize transplantation field. We're still using our own tissues. There's no risk of rejection. And in this case it will help boost the self-esteem of the patients who are going through a pre-traumatic experience. So they actually did a really nice news clip up there. Just an announcement. If you guys are curious. A woman who went to volunteer to be the participant in the first trial to test it back out. And she was crying and singing. And it was amazing. You know. It was a really bad event. When she heard you got a chance to check that out. And so. Yeah. Fact is able to improve her quality of life after that. It's really pretty. And I'm going to try and talk fast now. What was your temptation? You can't be somewhere. A little more detailed than this. But we're going to narrow it down. Very easy to remember. You can actually write them all together in one sentence. So a host can recognize as foreign. And mount a response against any histocompatibility antigen not encoded within its own cells. As a definition. Like I could be broken up in several sentences. I combined it into one pretty short sentence here. The outcomes and most types of tissue are greatly improved if donors have similar types. And so. That's what we call the histocompatibility. You're a liar. Antigens are similar enough. The body should hopefully recognize it as self. And so histocompatibility by definition describes two individuals with the same or near identical age-related types that will not mount a strong immune rejection reaction against each other's tissues. Because that's the worst thing that you can think of. Hey we just got transplanted kidney but oops. Our body sits foreign. And rejects the kidney and kicks it out. And then we don't have the kidney and we die. So it is pretty critical overall to have really matching here. We can talk about this a little bit more. Hypersensitivity. So even still. Allogeneic. We go back to definition here. Allogeneic. Where they are similar enough. Between slightly related individuals. These hands still have rejection. Very variety here. And they can't trigger their hypersensitivity reactions. So we talk about it with blood. Blood rejection follows very tight two hypersensitivity. We'll talk about what this means on Monday right now. Just memorize rejection of blood to two hypersensitivity. We'll talk about serum sickness. Maybe we'll again refer back to this on Monday here. But as you can see here from the different blood types. They differ in terms of what carbohydrates make it up overall here. You can see how there's an extra count on that. You can see that there's an extra count on A and gender. This is two lactose on A and gender here. And you don't have either of those on O here. And so the reason why it's called O is because they thought they were zero. And gender in the literature. So that's why the O's actually meant to be type zero blood. Because there was nothing. But now we have O. So they just wanted to add an A and B. And so it's basically on the type of liposome surface here. And so this is the main structure. All blood types don't think of the additional gal back. With type A blood here. And then this is gal with type B blood here. And so O individually has this core lipid. A has this one here. And B has this here. I'm going to give you AB. You have a mixture of these guys here. A and L. You have a mixture of these guys. You have B and L. You have this one and this one. How good? Very easy. Try to match those up. You don't have to memorize this. But you do have to loosely know which one might be in pattern. So this is the kind of picture showing what is a pan. What is an obviously green. Is anyone wearing green? The only one in the classroom. I'm not going to put it in. You are just email me and I'll pick a different colored graph. Because you probably can't see the difference. Here. So this is showing you what you can match. Because O is kind of missing any additional structure. O is one of the universal donors. And so this is showing donors in the sense that O can be given O. O can be given A. B and AB doesn't have an NP. You can memorize against A or B. And so AB can donate to A and AB here. As well as certain O's. And then you obviously can't give A to B. A to B here again. So you don't want to put anything that looks different enough that your body has no training on it. And then we respond to it. Who can remember the specific name of the antibody term that we use? So the type of antibody that responds to blood incompatibility. Do you guys remember where it's natural antibodies? Oh yeah. They're probably from E1 cells. And that's what actually contributes to a lot of our rejection of blood types. You guys all heard of resistance factor. It's an additional antigen on the surface that can, if it's positive. If it's negative it means it's not present. If it's positive it means it's present. We do additional matching with the resistance or the site how antigen is here too. And so the quickly important ones that we use are ADO and the resistance D or RHD factor. Interestingly, I learned this last year. If you actually look at every other new proposition of a new different blood type, like HLA science is super elaborate. There still can be as perfectly as possible. And there can still be rejection. And so then they go back and try to figure out why this patient rejected the new antigen that might have triggered an elicited new rejection response. And then they actually propose a new blood type that we should be using. So far these two have stuck and we haven't changed it. But many, many other ones that they do pose. If you go into HLA science, they do take action a lot of positions in this. So it's a pretty great field overall. But with it, they do also look at it. They have the ability to test for other antigen. They will look at it 2% in this creature. Say you're an immune back to the bus. Someone's bleeding out for a lot of people. Typically it's O. They're going to go pretty quick. Because then, you know, die now, die later. That whole argument there here too. O is not considered L-H genic because everyone has O pretty much. O negative and R-H-D negative people lack all three instances. They don't have A, B, and C-C-D. They're considered universal donors who can provide a transfusion to any other person. But unfortunately, they only receive blood from other O negative recess factor negative donors. A, B, recess factor positive people have all three instances of Christmas. And therefore, they're considered universal recipients. And so they receive blood from any other donor. But only donates to other A, B, recess factor positive donors here too. Bottom line is actually showing you the frequency of A blood types in the U.S. population. This is a little bit different. You can go by this point here. But notice that A, B negative is one of the rarest blood types here. If you're A, B negative, I highly encourage you to donate close. If you know you or others might need it. B negative is actually pretty rare too. Call it that. And then A, B positive is fairly low too. And then A negative and O negative a little bit less frequent. O positive is quite frequent. And A positive is actually quite frequent in blood type too. So pretty fascinating overall. And others are just going to talk about what are the hyper-acute rejection of a transplanatory to move from blood to talking about solid organ transplants here. This is also considered a type 2 hyper-acute reaction caused by pre-existing antibodies binding to the graft here. So this picture on the left side is highlighting this here. It is showing the antibody present. And so this kidney failure is transported, transplanted with a healthy alginic kidney so again. It seems easy to call it similar to possibly grafting here too. The patient antibodies against that donor blood, your antigens initiate an inflammatory response that blocks the blood vessels. If you block blood vessels, what does it get to the tissue? Blood, nutrients, oxygen, things that you need to keep tissue or organs alive. And so because of that, the kidney will become forged and purple colored because of massive hemorrhaging and clotting within the kidney. The kidney will fail and the patient will die from a hyper-acute reaction. Call it hyper-acute because you can guess how quickly it happens. Very fast. This is typically because there are antibiotics for some reason within that patient that rejects this transplant tissue very, very quickly. And we reject it almost immediately. There's a delayed type reaction where it takes a few years for the tissue to start judging us more than life because slowly over time the host remains and then slowly builds a response and gradually attacks the tissue. This is for pre-existing. That's already there. It attacks very, very quickly. And unfortunately, it leads to that type 2 acute hyper-sensitivity. Type 2, hyper-sensitivity, hyper-acute rejection overall. So that's one example here too. Another example of that right here. You can have anti-aculate antibody rise from pregnancy, blood transfusion, and prior transplantation too. So let's talk about example with pregnancy specifically because the mother and father have different HLA class 1 and class 2. Remember, HLA class 1 is also synonymous with MHC1. HLA2 is with MHC2. But unfortunately, we were just solely talking about human antigen at this point. That's why we refer to it as HLA because it's human, but HLA2, MHC2, HLA1, MHC1. And so during the station, especially if these cells are not supposed to be in the mother's needs, there is some selective permeability of MHC2. But usually during birth-to-mother reaction, that when a very traumatic birth process, at some point there will be exposure either to the mother to fetus or to the fetus to the mother of other cells, like potentially a boundary reaction. So it's usually not risky for the first pregnancy because again, you need to develop an immune response to something. Let's say I'm a negative, I'm pretty sure my husband would be positive. If we ever have kids, if the first child ends up being positive, I won't most likely mount an immune response for pregnancy. If we ever go to have kids that time there is a risk, especially if it's positive, at this point my body really doesn't have antibodies against the positive blood. You can't have spontaneous abortions because the body recognizes the fetal blood is being born and causes an ******** and rejection. Why is it all very important to catch pregnancy early too? Jack, especially if you know your husband or a different part of his blood type, verify with him, kind of apologize. At this point, he will tell you about this next week. At this point, especially if you know you're pregnant, you know that your parents have different blood types. They'll just put on a road ramp off the spot to help lock that reaction regardless. Let's talk about road ramp a lot more next week. That's like standard care now. Road ramp for everybody is a very safe drug. It's not going to hurt you if you don't need it. So it's just better to be safe. Sorry, I just put everything on the road ramp. Let's go to the access of testing. So in acute, we just talked about hyperacute reactions. Now we'll talk about acute. We're still fast, but it's not as fast as like within the first week or so. And so graft versus host disease is another one we're talking about. So a chance at rejecting is host rejecting the new transplant tissue. Graft versus host actually where left over cells within the transplant attack the new host and then inject it too. Graft versus host is fatal in life. I'm pretty sure every instant I've heard of a single one where they've actually been able to save up the patient after their graft versus host has taken hold. I just want to talk about how quickly they pass away from it. Both acute transplant rejection and graft versus host are going to take type 4. Hyperacute disease is a delayed type. It takes a little bit longer to kick in. Because if you have a kidney or solid organ transplanted, if the recipient's T cells start attacking the organ, it leads to acute transplant rejection. Versus you transplant a kidney or a liver or something. Or even bone marrow. There's a left over T cell in there. That's something that looks already similar enough to host transplanting in it. It's like an evil army. It's like how many people tell you what to do. It goes out and it's like you need to show yourself. Go kill it. Go take care of it. I'm a T cell. I know what I'm doing. You should kill these things. That's what's happening. So it takes a little bit longer. Especially going with one cell. Like a left over. Unfortunately, it leads to where it leads to the telomeres of the very, very similar recipients to start attacking and killing itself. And Robert's host is an incredibly horrific disease overall. Both of them fall under type 4 because they're delayed. They take a little longer. We'll talk about how type 4 is just known as being a delayed type of sensitivity here. Organ transplantation does involve diseases that produce inflammation and the donated organ implants that recipient. Anytime you have an inflammatory condition, your immune system is activated already. So it's like pulling a firearm that we're already looking for danger anyway whether danger exists or not. It makes me more like to see something because of the alarm going off telling me something bad is happening. So when you have inflammation, it already kind of crimes you and stuff you up with this negative consequence of potentially having an injection here. So this is a good example here of showing a traffic accident, provides a kidney transplantation before the person is now deceased. They, you know, it's, he went through the trauma of death. They had then cut out the kidney. Why it transplants? I just wanted to say, I think that patient's called the transplant center. And again, they splurge with the cup of tea to go to bed. Remove one organ and put the new organ in. It's a very violent address process. There's a lot of inflammation in the body. So it does prime it for kind of immune activation anyway. So we'll frequently put immunosuppressant in to try to help control that process of going through. Usually a patient about to receive a transplant is put on immunosuppressant very quickly. Suppressant is as fast as possible to do transplant. And kick up the body a little bit at a time to recover hopefully. We'll stop there and then we'll pick up a little bit more detail. It seems like a lot of patients will go through it slowly. You get stuff that we know. It's pretty cool size overall. And they pay really, really well if you go on a transplant site. As a DO, PhD, MD. Please pay really well. Cool.