This lecture is all about disorders that have to do with the immune system. We've learned a lot about the immune system, the cells that are involved, the different processes involved in your immune response, and so we're going to see a lot of these terms, a lot of these processes come up when we talk about diseases of the immune system. So before we go into the different types of disorders, let's talk a little bit about something called the hygiene hypothesis. The hygiene hypothesis basically states that the more we are exposed to pathogens in our everyday life, that means we're going to be less sensitive to allergens and things that are going to cause a reaction. So for example, people who have grown up on farms, people who are part of tribal populations, they're exposed to a lot of things, right? Like if I grow up on a farm, I'm exposed to a lot of dirt, the outside nature, animals, and so I'm going to have less allergies, less asthma compared to someone who's grown up in the city. And nowadays, we have way less exposure to pathogens because we're in really clean environments, right? We have disinfectants that we use, right? We always wipe our benchtop in lab. We're always using sanitizer and hand soap. And so, we live in a really clean environment, which makes us more sensitive to allergens. And so, nowadays, we have way higher asthma rates. We have a lot more cases of allergies. And this is because of our um lack of exposure. Okay. So we become hyper sensitive. We start reacting to things um way more intensely than we should. For example, pollen outside, dust, um cat fur. It's really not harmful to us. It's not going to do anything to us. But for some reason, when we have allergies to these things, we are kind of overreacting to them. This is called hypers sensitivity. Hypers sensitivity is when your antigenic response is beyond normal. It's too high. It's an overreaction um that's going on. And in this lecture when we talk about antigens, we're talking about allergens. And this is because we're talking about um allergies and hypersensitivity. So an antigen, if you recall, it's anything that triggers an immune response. That antigen can be a foreign antigen from a pathogen that's entered your body. It can be even a self antigen which is a molecule on the surface of my cells that belongs in my body. Or the antigen can be an allergen, a pollen grain, dust, a sort of plant, whatever that is that's causing that hypersensitivity. Now there are four types of hypersensitivity reactions. We have anaphylactic, cytotoxic, immune complex, and delayed cell mediated. And when we're studying all of these types of hypersensitivity reactions, we call this study immuno pathology. Literally, the immune system's diseases. So again, there's a definition of the hygiene hypothesis. So, when I limit exposure to pathogens, then I'm going to have a harder time coping with antigens and allergens that are basically harmless to me. Make sure you know and you're able to explain the hygiene hypothesis. So, let's look at type one hypersensitivity reactions. This is also called anaphylactic reactions. This occurs just minutes after someone is sensitized to an antigen gets reexposed to that antigen. So it's kind of like the second exposure to that allergen causes that over reaction. So you've been exposed to it before, you've been sensitized to it and now you're reexposed to it, whatever that allergen may be. So what happens during a type one or anaphylactic reaction? We've learned about Ig antibodies before and those were the antibodies that we learned are involved in allergic reactions and we've learned about basoils before that are our immune cells. We've learned that they are also involved in allergies and they release histamine. So during an anaphylactic reaction your IG antibodies bind to your mast cells and your basopils and once that binding happens mass cells and basopils undergo a process called degranulation and that's when they start releasing these substances called mediators. The three types of mediators that are released are histamine, lucotrien and prostaglandins. These three types of mediators are what's going to cause all of those symptoms. So, if you've ever taken like an allergy medication, that's an anti-histamine. It's going to block this histamine so you don't feel all of those allergy allergy symptoms like runny nose, watery eyes, whatever it might be. Now, there are two types of anaphilaxis and it can be really really serious or it can be mild. So the serious anaphilaxis or the severe anaphilaxis we call it systemic. That means that it involves the whole body. This can also be called anaphylactic shock which you may have heard of before. So that's again when you've been sensitized to an antigen and you get exposed to it again. This can lead to circulatory collapse and it can be fatal. So these are the cases where you'd have to carry an EpiPen with you which is epinephrine and you'd have to inject yourself to basically save your life. Localized anaphilaxis means that it's just in one area and the symptoms really depend on how it entered into the body. It's usually either something that we inhaled or something that we ingested. So if you ate something you're allergic to, if you inhaled something you're all allergic to. Some examples of localized anaphilaxis can be like hives in a certain part of the body, asthma, which has to do with inhaling um antigens. So that can all cause localized anaphilaxis. So here on the left are just pollen grains, just harmless pollen grains, but for some reason some of us are hyper sensitive to them. And here is a dustmite. A lot of us are also allergic to dust mites and it's actually on like carpet or something. So how do you prevent anaphylactic reaction? So there is a treatment and it's called desensitization. So you're literally making yourself less sensitive so you won't react to a certain allergen. So, this has to do with injecting that antigen just a little bit and increasing doses just beneath the skin like right under your epidermis little by little um maybe like once a month or something and that's going to get your body used to it. It's going to help you produce IGG antibodies so you can neutralize the antigens um and you won't react to them anymore. That's desensitization. So little by little little tiny dosages of that allergen is are injected so you get desensitized so you won't react to it. This is an allergy test. So a skin test um where again you inject different types of allergens just underneath the skin and you see if there is a reaction. So if it's red, we call this like a wheel. It's kind of like this uh rapid inflammatory response where it's redness around a bump. Um, these are basically a reaction. So, this is an allergy test that's done. Um, and they inject with all different types of like different types of plants or trees and fur and pollen and so on. Okay, moving on to type two reactions which we also call cytotoxic. What does cytotoxic mean? That means toxic to the cell. Right? Now during the cytotoxic or type two reaction the complement pathway is activated and remember one of the outcomes of the compliment pathway was cytosis right which means cellis. So that's what can happen. So a big example here is the blood group. In the blood group system which we've talked about before you have antibodies against antigens that you don't have. Right? So if for example I am blood type A that means I have the A antigens on the surface of my red blood cells and that's normal. If I'm blood type B then I have B antigens on the surface of my red blood cells. What if I have no antigens on the surface of my red blood cells? I don't have A and I don't have B. Then I would be considered type O. What if I have both A and B antigens on the surface of my red blood cell? Then I would be type AB. So whatever antigens I have on the surface of my red blood cells, that's my blood type. And whatever antigens I don't have, I have antibodies against it that I'm born with. So for example, if let's say here's my red blood cell and I have A antigens on the surface, this means that my blood type is type A. And do I have antibodies against A? No, because I'm not going to have antibodies against my own antigen cuz then my antibodies are going to attack this red blood cell and basically lice it and kill it. Do I have antibodies against antigen B? Yes, because I don't have B on my surface. So, I'm going to naturally have antibodies against B. What if I am blood type A? So, that means on the surface of my blood cell, I have A and B antigens. So, in this case, do I have antibodies against A? No. Do I have antibodies against B? No. What if I'm type O, right? And so I don't have A or B antigens on the surface. Do I have antibodies against A? I do because I don't have A antigen. Do I have antibodies against B? Yes, because I don't have B antigen. So that's how the antigens and antibodies work. Now we're going to add on to this information and we're going to talk about something else called an RH factor. Now, an Rh factor or Rh antigen is what makes your blood either positive or negative. So, maybe you've heard of like A positive, B negative, AB positive, AB negative, O positive, O negative. So, what is this positive and negative? So, there's another type of antigen on the surface of our red blood cells called Rh. So, it's pretty simple. If here's my red blood cell. If I have the Rh antigen on the surface of my red blood cell, then I'm positive. If I don't have the Rh antigen, then I'm negative. That's simple, right? If I have it, it's positive. If I don't have it, it's negative. However, the antibodies are a little bit different here compared to Like remember, whatever antigen I don't have, I don't have antibodies. Oh, whatever antigen I don't have, I'm born with antibodies against it, right? Like if I'm type A, then I have antibodies against B. And you're born with those antibodies. However, our H factor works a little bit differently. This one works kind of like a typical cold or infection. For example, let's say I had corona virus last night uh last month, right? I had COVID last month and now I made antibodies against CO. Was I born with antibodies against CO? No, it was just based on my exposure, right? The Rh factor antibodies work the same way. So if I am negative, meaning I don't have Rh antigen, I don't necessarily have antibodies against Rh. I'm not born with antibodies against Rh. Only if I'm exposed to Rh positive blood, then I would make my anti-R antibodies. Now this is a really big deal when you think of pregnancy and when you think of blood transfusions because the blood has to be compatible. So what happens during pregnancy? So let's say a mother is pregnant with their first child. Okay. Now the mother is Rh negative. So she does not have Rh antigen in her blood. But she's also not born with antibodies against Rh because she's never been exposed to positive blood. However, her first baby has Rh negative blood. Uh, sorry, her first baby has Rh positive blood. So, what's going to happen when the mom's blood cells come into contact with the baby's blood cells? That's in other words, the Rh negative blood is going to come into contact with the Rh positive blood. Now that there's that exposure, now the mom is going to make antibodies against Rh. Now that's fine for the first baby. She came into contact with it. She was exposed to it and then she made antibodies. Now, if she got pregnant with her second child and that second child is also Rh- positive, that's when it becomes a big deal because now that she has antibodies against Rh, what's going to happen? The antibodies are going to attack the baby's red blood cells and lice them. This is called hemolytic disease of the newborn. Okay? So again the mom is Rh- negative the fetus is Rh positive. First baby she gets exposed she makes antibodies against Rh. Second baby her anti- Rh antibodies are going to damage the fetal red blood cells if it's Rh positive baby. So that's hemolytic disease of the newborn. Very very serious because basically all of the newborn's red blood cells get attacked and they lice. Right? This is cytotoxic. So it leads to cell lis. Okay. Now there can also be drug induced cytotoxic reactions. For example, th uh thrombocytoenic perpa. This has to do with thrombocytes which are another word for platelets. So some drugs they can combine with platelets and they form a complex that your body considers an antigen. So it's going to trigger an immune response. It's going to trigger antibodies and complement to lead to cytosis of those platelets. So your platelets end up getting attacked which is bad. We need our platelets for blood clotting. Hemolytic anemia is another one. So this is drug induced destruction of your red blood cells and if your red blood cells are being destroyed then that's a form of anemia. Okay. So type three hypers sensitivity reactions are called immune complex reactions and that's when you have antibodies that form against antigens in the blood and whenever they um kind of bind together we it creates something called an immune complex and these immune complexes kind of lodge themselves in the cells. So it's specifically in the basement membrane of the cell. So, let's say I have a bunch of cells, right? They're next to each other. They're making up a tissue. Whatever that tissue is, all the cells are together making up a certain organ in your body. And they're all attached to this base. Okay? And this is called the basement membrane. And so this basement membrane is where these immune complexes kind of lodge and they go in here and they kind of get stuck in here and they're going to cause an impairment in the function of that tissue. This is going to activate compliment and again one of the outcomes of compliment is inflammation. So it causes inflammation in that individual and immune complexes can be formed in different parts of the body. We'll see a couple examples of that soon. Now, type four hypers sensitivity reactions, we call these delayed cell mediated, we can also call them delayed hypersensitivity reactions. These are caused by TE-C cells, right? Remember cell mediated immunity. That main player in that process were TE-C cells. So, antigens undergo fagocytosis. they're presented to TE-C cells and the TE-C cells get sensitized to whatever that antigen or allergen is. Now, when you're reexposed, now you have memory cells um that are basically going to release cytoines and destroy that antigen. So, it's kind of like your typical adaptive immune response, but this time it's to a random allergen that's normally harmless. And remember with your immunes with your adaptive immunity that one has memory. So the second exposure it's going to have a more intense stronger um attack on that antigen. And so that's why it causes a lot of symptoms. So one example of delayed cell mediated reactions are allergic contact dermatitis. Dermatitis has to do with inflammation of the skin. So, this happens when, let's say, you're in contact with something. So, it's always going to be with direct contact, either like you touched a poison ivy plant, you put a certain type of um makeup on your face, a latex allergy, you came into contact with a certain metal like silver that you're allergic to, maybe like a piece of jewelry. So normally these things like poison ivy, cosmetics, latex, whatever it is, they have these substances, these molecules called haptins. And the haptins in these products or items, these are normally harmless. But when they combine with our skin proteins, that's when they trigger an immune response. So again haptins normally like let's say this is poison ivy there are these molecules that are haptins normally harmless but when they combine with the proteins in my skin like when my skin is in contact with poison ivy it creates this complex that triggers your immune response and that's when you're going to feel those symptoms. For example uh poison ivy you get like these itchy rashes um and it's kind of bumpy. Okay, we're going to talk now about autoimmune diseases. So, what do we think of when we think of like an autoimmune disorder? We think of it something attacking us, right? Our body attacking itself. So, in an autoimmune disorder, there is a loss of self- tolerance. This means that your body and your immune system and your immune cells, they cannot tell the difference between what belongs in your body and what doesn't belong in the body. they can't differentiate between self and nonself antigens and so that's a big problem because then they start attacking our own self antigens that's autoimmune now autoimmune diseases can be with cytotoxic reactions immune complex and even delayed cell mediated so let's talk first about cytotoxic autoimmune diseases the first or actually the only example that we're going to talk about with cytotoxic reactions is multiple sclerosis. You might have heard of multiple sclerosis before uh abbreviated as MS. In this disorder, in this autoimmune disorder, you have auto antibodies. They're these abnormal antibodies and you have TE-C cells. You have macrofasages that basically attack your own myelin sheath of your nerves. So, let's talk about first what myelin sheath is. So, your nerves are part of your nervous system, right? They help you feel things. They help with your movement. And your nerves are always signaling to your muscles. So the nerves, we call them neurons. They're like the simple form of a nerve. And neurons communicate with each other. And they communicate really, really, really quickly. For example, if let's say you're in the kitchen, you turn on a pan and you're going to cook and then you forget that that pan is on, right? That the stove is on and you accidentally put your hand on the hot pan. What are you going to immediately do? You're going to immediately take your hand off, right? You're going to yell, "Ouch!" and you're going to take your hand off. Well, that's how fast your neurons communicate. The second you feel that heat, you immediately took it off. But during that time, all your nerves from the tips of your fingers from your hand are sending a message all the way to your brain. Your brain is processing what's going on. And then your brain is sending that sending a message to your muscles again through a bunch of neurons. It's kind of like a pathway of neurons all the way to your muscles to help you pick your hand up so you don't burn yourself. That's how fast a bunch of these nerves communicate with each other. So what does this have to do with MS? Well, one reason why nerves communicate so quickly, like a split second, is because they have this covering. They have something that kind of surrounds the nerves. It covers the nerves and this is called a myelin sheath. So the myelin sheath insulates your nerves and allows them to have really really fast signals, really really quick impulses. So without myelin sheath, your nerves are going to communicate very very very slowly. So if for example in a healthy individual, you'd pick your hand back up from that hot pan really quickly. If my nerves do not have myelin sheath on them, then it's going to be really really slow. It's I'm going to take really really long to pick up my hand because that signal is not being passed around fast enough. So in MS, your te- cells, your auto antibodies, your macrofasages are attacking and killing the myelin sheath surrounding your nerves. And so you are going to deal with fatigue, weakness, even paralysis where your muscles just don't even work. Keep in mind that without getting a signal from your neurons or your nerves, the muscles are not going to be activated. Your muscles are not going to contract. So I can have the most amazing perfect muscle ever in the entire universe, but without getting a signal from a nerve, that muscle is not going to move. that muscle is not going to do anything. It's going to be paralyzed. So that's why this is so important and that's why people deal with weakness and they feel a little bit more slow because they're missing this myelin sheath. Okay. So let's talk about some immune complex autoimmune reactions. So this again has to do with these abnormal antibodies in the body. Now there is two examples of this. Graves disease and mymia gravis. Graves disease has to do with these auto antibodies that are in the thyroid gland and they cause the thyroid gland to produce excessive amounts of thyroid hormone. So the thyroid gland is one of your endocrine glands. It releases thyroid hormones and so it kind of causes your thyroid gland to be overactive and just keep producing producing producing thyroid hormones more than it's supposed to. So the symptoms of Graves disease actually mimic hyperthyroidism which is another condition which is treatable. It's not an autoimmune gravis also antibodies but these antibodies are blocking the signal from nerves to muscles. So I mentioned that neurons or nerves they have to send a signal to the muscles for the muscles to act right or to get activated and contract. And the signal that they send to the muscles is in the form of a neurotransmitter called acetylcholine. So acetylcholine is the se is the signal. So let's say if I have here's my neuron cell. I'm just going to do this for to be simple. And here is my muscle cell. So what the neuron is actually sending to the muscle is acetylcholine. Okay? This is a neurotransmitter and that's the signal that the muscle receives. Now, the muscle has receptors for acetylcholine, but you have these antibodies that are going to go in and they're going to block this receptor. They're going to sit in this receptor and so now acetylcholine is not going to be able to be sent to the muscles and so the muscle again if it doesn't get the signal it can't move. And so in myia gravis your skeletal muscles um stop being able to move. It starts with the eyelids. You can't open up your eyelids. You get droopy eyelids and then it can spread to other parts of the body. So it's basically like paralysis. And then by the way with the Graves disease when I mentioned that it mimics hyperthyroidism one of those um symptoms or signs is a really really enlarged thyroid gland. So there's like this big bump um in like the anterior neck. Okay. Couple of other examples of immune complexes. One of them is lupus which maybe you've heard of before. The entire term is systemic lupus arythmatitosis. And this is where immune complexes form in the kidney glomeriuli. What is the glomeuli of the kidney? Glamuli are these little tiny structures. you have a bunch of them inside your kidneys and they help filter your blood and get rid of waste. And so if you have a bunch of immune complexes lodged in the glomemeuli of your kidneys, that's going to be a really really big problem. It's going to impair the functioning of your kidneys. It's going to impair your ability to filter and clean out your blood and get rid of waste. So a lot of times lupus patients, they have to get a kidney transplant. rheumatoid rheumatoid arthritis or RA again same idea but in this case immune complexes form in the joints so there's a lot of joint pain because these immune complexes are building up inside of the patient's joints okay an autoimmune diseases that have to do with cell mediated reactions so this one is going to have to do with teac cells so you have tea cells that are not acting like they're supposed to tea cells that are attacking your own cells cells. So, we've all heard of diabetes before, right? There's two types of diabetes. There's type 1 and type two. Type 1 diabetes malitis is also called insulin dependent diabetes malitis. That's the one that someone is born with. So, the person is born with this autoimmune disease. And this is when TE-C cells attack and destroy the cells in our body that release insulin. Insulin is a hormone. It's released from cells inside of your pancreas and it is there to basically store glucose. So if I have like a really big meal right now and I eat my meal and I finish it, I have a lot of sugar in my blood. I have a lot of glucose in my blood. Insulin then gets released and takes that glucose and stores it inside of my cells for energy. If I don't have insulin getting released, then I'm going to have sugar left in my blood and no one to tell it where to go. And that's why diabetes patients have high blood sugar. So again, the cells in the pancreas that release insulin get destroyed by tea cells. And so that's why these individuals have high blood sugar because they don't have insulin getting released. Another example of a cell mediated autoimmune reaction is psoriasis or seroriatic arthritis. Again, same idea, but te-c cells are destroying the skin. So the skin cells are constantly being killed off. Um and so that's why you have like this really like flaky exfoliated like skin. Um this slide is just um what we talked about plus more um examples of autoimmune diseases. So there's extra information in here if you're curious. Now when someone has for example a transplant of an organ, a kidney transplant, whatever it might be, there's a high chance of rejection, right? So the recipient's body can reject that donated tissue or that donated organ. So that's why blood typing is really important because you want to make sure the donor and the recipient have compatible blood types. And another thing that's important is tissue typing. and tissue typing we do with MHC genes. Remember we learned about MHC type class one MHC class 2 genes. MHC in humans we call these HLA. And there's a bunch of different types of HLA. They're all signified by like a number like HLA 12, HLA1, whatever it is. And depending on the types of HLA genes that an individual has that is related to their susceptibility for developing certain autoimmune diseases or other genetic diseases. So looking at the HLA types in an individual and testing this is tissue typing and that's another big part of transplantation. Okay. So there are also privileged sites or privileged tissue in our body. Now remember transplants they can be attacked by the recipient's tea cells their compliment system um antibodies macrofasages but there are some parts of the body where you won't get an immune reaction. You won't get a any chance of rejection. Um one example of that is coral transplant. So if someone has a corneal transplant, which remember the cornea was the outer layer covering of the iris of your eye, it's like a clear covering. Um if someone gets that donated, there's no reaction that's going to happen there. So no risk of a rejection as well as heart valve transplants. So transplantation of heart valves. Um that's a privileged tissue. So you won't get an immune response. So nothing's going to get rejected. Let's now talk about stem cells. Remember that stem cells, we call them master cells. They can turn into any type of cell. That's called differentiation. So they can differentiate into any type of specialized cell in the body. They can turn into a blood cell. They can turn into a liver cell. They can turn into a skin cell, a bone cell, whatever it might be. And so embryionic stem cells um are stem cells that are taken from blastois. Blastois is basically um the structure before it turns into an embryo. So a really really really premature um and you take these stem cells from the blastois and you can use these stem cells to regenerate types of tissues and organs by basically making those cells specialize into a certain type of cell whatever cell that you need. An example of transplants are bone marrow transplants, also known as hematopoetic stem cell transplants. And that is when a recipient, an individual needs help producing healthy blood cells, they can have a bone cell uh transplant or bone marrow transplant. Okay. Now whenever someone um gets tissue like donated tissue um it can be from another individual or let's say someone is a burn patient and their arm needs a little bit of extra skin. They can get skin from another area of that patient's body and basically transplant it or graft it onto let's say wherever they're missing the skin. Right? So grafts can have different sources. So an autograph is when you use your own tissue. Isograph is if you're lucky enough you use an identical twins tissue. Allographs are getting donated tissue from a whole other person. And then xenographs are using nonhuman tissue. So there's a bunch of different types of grafts. And I mentioned earlier that the recipient's body can reject these grafts, right? Like if it's from a different person. However, there is a disease called graft versus host disease, and that's when the opposite happens. The donated tissue can attack the recipient's body. So, that's graft versus host. Let's talk a little bit about cancer and the immune system. Now, normally cancer cells are removed by a process called immune surveillance, right? There's always all of these checkpoints. cells. Uh we don't our body doesn't allow cells to divide if they're defected, if the DNA is mutated. However, we know that there's a lot of genes that can be turned on, it can be turned off to turn a cell into kind of like a constantly uncontrollably dividing cell. So cancer cells, they divide uncontrollably, right? We've learned how they don't have any contact inhibition. And whenever a cell turns into a cancer cell, there are antigens on the surface of these tumor cells that are considered nonself. They're considered foreign. So we our tea cells, our macrofasages, our natural killer cells actually do attack and kill and lice these cancer cells. However, cancer cells, they don't have like a one consistent type of antigen that our body can recognize. They're always mutating. The tumor cells are always dividing way too fast for our immune system to keep up with. Also, tumors, remember when the cells kind of they lose contact inhibition, right? So, they're building up on each other, creating this mass, this tumor, they slowly start to gain blood vessels, they vascularize, and so they get blood circulation, and that kind of lets them hide out from the immune system. So, the immune system won't recognize them as something foreign. and it'll just be like another type of tissue in the body. There's a lot more to cancer and the cancer processes. You can teach an entire class on this but this is as much as we need to know for this um topic. Now we also have immuno deficiencies. Immuno deficiencies are when the immune system is not sufficient enough. Maybe someone um doesn't have normal tea cells. Maybe someone is born without B cells. Now someone can be born with an immuno deficiency. Um they can be missing the genes. They can have defective cells. In this case we would call that congenital immuno deficiencies. Anytime you see the word congenital think of the person is born with it. Acquired immuno deficiencies are immuno deficiencies that develop later in a person's life. This can be due to cancers, different types of infections, different types of drugs. And so the one main example that we're going to talk about now to at the end of this lecture is AIDS. That literally stands for acquired immuno deficiency syndrome. And AIDS is caused by the virus HIV which we've talked about before. Now the first in the beginning before we even discovered what HIV was it was early8s there were a lot of cases in the US of pneumonia a specific type of pneumonia called pumoscystus pneumonia that's caused by the agent numoccystus gurovichi there was a certain type of cancer called caposis saroma that was getting um common in like a bunch of cases and this pneumonia and this cancer was also linked to a loss of immune function. So it wasn't your typical pneumonia or your typical cancer. It was causing an immuno deficiency in the patients who had this infection. And so they noticed that this is something really weird. Why would this pneumonia cause someone's immune system to fail? Why would caposio saroma cause someone's immune system to fail? They were like this is something else. And so they researched and that's when the discovery of HIV happened. And they learned that HIV causes the loss of immune function. And we discovered that HIV virus specifically infects T- helpper cells. Remember these CD4 T- cells that we've learned about? They play a big role in not only innate but also the two types of adaptive immunity. They help B cells, they help T- cells. they do a lot these CD4T helper cells and that's what gets infected with HIV and that's why these individuals immune function was getting debilitated basically. So let's talk a little bit about the structure and life cycle of HIV and how it infects the CD4T cells. Now HIV is a retrovirus right? So it's a it it's made up its genetic material is made up of two um positive sense RNA strands and remember it's a retrovirus. So it performs reverse transcription with the reverse transcriptise enzyme. So using that reverse transcriptise enzyme it can turn its RNA into DNA. And if you recall, it can then integrate its viral DNA into our host chromosome, our own DNA. HIV viral particle is also enveloped. So it has an envelope surrounding it and sticking out of the envelope, you have these spike proteins which are called GP120 spikes. So here you have the HIV particle, right? You have the envelope surrounding it. So here again is the envelope. And remember the envelope is just like the same material as the plasma membrane that surrounds our cells. You have these GP120 spikes sticking out. You have the singlestranded RNA in here. Reverse transcriptase enzyme. You also have an enzyme called integrace. What do you think integrace does? It helps integrate. So it's going to help that integration of viral DNA into host cell DNA. Okay. So how does HIV actually infect or enter into CD4 T- cells? So here on the left you have the HIV viral particle and then here on the right you have the CD4T cell. CD4T cells have certain types of receptors on their surface. you have the CD4 receptor and it also has a co-ceptor which is either going to be CCR5 or CXCR4. So this HIV particle using its GP120 spike protein it binds to the CD4 receptor as well as the co-ceptor and in that way it starts fusing its viral envelope with the plasma membrane of our cells and then it has entered into the CD4T cell and infected it and remember the core receptor can either be CCR5 or CXCR4 so that's how it attaches fuses and enters enters into the host cell. Now inside of the host cell, remember the RNA under goes reverse transcription into DNA using that reverse transcriptise enzyme and then the DNA gets integrated into the host's chromosomeal DNA using the enzyme integrace. Now this can be an active infection where it multiplies and then it buds out and it fuses out of the cell and goes on and infects more and more cells. Or it can be a latent infection where it just lays dormant. The DNA just hides in the chromosome. In that case, we call it a provirus and it just stays there and you don't feel any symptoms. Now HIV, there's a lot of problems and challenges we have with HIV. One of which is that it mutates a lot. It mutates really quickly. It mutates just in a single individual's body. it under goes a bunch of these antigenic changes, changes up its surface molecules, mutates its proteins, and so it's really hard for our immune system to keep up with it. So, let's talk a little bit about the symptoms of HIV and the signs of HIV. Now, an HIV infection has three stages. In stage one, that's when the individual first gets infected with HIV. And so either they can be asymptomatic, meaning they don't feel any symptoms, they feel just totally healthy. Or they can deal with um flu like coldlike symptoms. So they think, "Oh, I just have a cold or I have a fever. I have the flu." And then they get better and they're like, "Okay, I healed from this cold or this flu or whatever it was." And then we get into phase two. During phase two, you don't really feel anything for a number of years. You can go on for like 8 years, 10 years. and nothing's really happening, but you get sick more often than normal. And during this time, your CD4T cells are slowly declining. You're slowly losing. They're dying out. These CD4T cells are dying slowly during this phase. Once the CD4T cells reach under 200, meaning I have less than 200 T-H helpper cells in my body, that's when we enter phase three, which is officially an AIDS disease. And during AIDS, if someone has AIDS, they are going to be really susceptible to every type of infection. any germ, any bacteria, fungus, virus, protozoan that they are exposed to, they're going to get infected by it because their immune system is deficient, right? It's not working cuz they don't have any CD4T cells anymore. So these are the three phases of the HIV infection. Okay. Um so initially right during phase one you have enough CD4T cells so you resolve that first infection but as it goes down you can't fight off the infection and so this table shows a lot of these common diseases that are associated with having AIDS. So you can see a lot of different categories different types of bacteria fungi cancers and so on and you uh you just get hit with multiples at a time. Okay. So obviously um some populations are more susceptible to HIV infection survival. For example, older adults, their immune system is not functioning as well as it used to. Young children, they don't have a fully developed immune system yet. So they're more susceptible to not surviving as well with HIV infections. Now there is a population of people that have a mutation in their CCR5 co-ceptor. So if since they don't have or they have a mutated CCR5 co-ceptor, even if they get exposed to HIV like a million times, that HIV is not going to be able to enter into their CD4 cell. So they're not going to be infected. Okay. How is HIV transmitted? a lot of different types through sexual contact. It can be through breast milk from mother to newborn. It can be transplacental from mother to fetus, blood contaminated needles, like if someone is a drug user and um they're reusing a new needle from someone else and there's contaminated blood in there, organ transplants, blood transfusions. Um these are all ways that HIV can be transmitted from one host to another host. Now, anal receptive intercourse is the most dangerous form of sexual contact for HIV. And that's because with anal intercourse, the anus, the tissue of the anus is very very very thin. Um, and so it easily bleeds. It easily um rips and so with analcourse um high chance of bleeding, high chance of blood contact. So nowadays, AIDS is considered a treatable disease. It's still a chronic disease. We still don't have a cure, but it is treatable. You can live with it. You can still have a good quality of life. And with AIDS therapy, this is called heart or highly active anti-retrovir viral therapy because it's a retrovirus. And with this therapy, um, the patient gets prescribed a combination of drugs. is like a cocktail of drugs, maybe like four drugs at a time that target different parts of the viral process or the viral molecule and then every year or so they switch up the drugs and that's because we have to keep up with HIV because it mutates so fast. So that's why it's so important to know all of these different steps and enzymes and proteins and structure of the HIV virus, right? Of the viral particle. Why? because we want to find drug targets. So we have drugs that inhibit the fusion of HIV, the entry of HIV into our host cells. We have drugs that inhibit reverse transcriptase or inhibit integrase or inhibit protease which helps make a lot of the proteins of HIV. And so you can use different drugs that target different points all at the same time. And so this is part of HIV therapy. So lastly, I mentioned there are challenges with HIV therapy and developing a developing a vaccine and cure for HIV. One challenge is that HIV only infects humans. So it's really hard to research with. And if and we can't inject HIV into a human and treat them like a test, right? Um that's unethical. If let's say we want to test it on mice, like lab mice, it's not going to be exactly the same way as it would in the human body where we know a lot about retroviruses, but we're still learning about retroviruses. And the more we research, the more we learn and add to this research, the more chance we have of the treatments. And like I mentioned, HIV has a high mutation rate. It leads to a lot of resistant uh strains. It's always mutating. It's always changing. So again, it's hard to keep up with.