Chapter 19
Chapter 19. Hypersensitivity reactions are disorders that are involved that involve the immune system are discussed here, but also we're going to talk about what happens when our immune system fails. For example, infection, it happens when autoimmune system fails to to eliminate the pathogen and so therefore the pathogen takes over. Cancer is also a failure of the immune system because we do have those natural kill ourselves, for example, that are involved in what's called immunological surveillance, which their function is to just travel throughout the body and look for abnormal cells such as cancer cells, which is a that is a reason for. Actually seeing cancer more in elderly because the immune system is breaking down or or very the very young or the immune system is not is not mature yet. And also and of course, immune system. Speaking of aging, immune system also starts to break down and is not as effective in elderly as you age or your immune system becomes less and less effective. And in addition to aging, there are some drugs that are taken on purpose in order to depress the immune system. For example, a few that we're going to mention, this chapter that are used are prescribed for people who have. Undergone a tissue or organ transplant and and also some cancers depress the immune system. And. Next, we're going to talk about autoimmune diseases, so these are the they're a bunch of diseases that are known to mostly affect women. There's a genetic predisposition. And by that I mean just. That the genetic, I should say, gender predisposition, just being women, a woman is going to make you more susceptible to develop an autoimmune disease, an autoimmune diseases are those that happen as a result of the loss of self tolerance, meaning that the immune system itself has lost the ability to differentiate itself from non self molecules. Charles, transplant rejection is an unwanted immune response. Same thing with blood transfusions in case that it's a transfusion of income in compatible blood type. That's also. Unwanted, unwanted immune response, hypersensitivity or allergic reactions are also all unwanted immune response, allergy is a is an immune reaction that is beyond that is considered normal. And here in this slide, you you can see some of the most common allergens. So allergens are substances that in some people they provoke and exaggerated immune response.
And of course, they are saying, but they're actually there have been studies since 1970s where there they have. For all of a sudden, they've been noticing that there are more cases of allergy allergies, including food allergies and.
Also, cases of asthma increasing and now they call it the hygiene hypothesis,which really the study is sort of the 1970s, but they've noticed that increasingly in the urban area as opposed to farmlands where kids are more exposed to different kinds of microbes, including, you know, parasitic worms, the incidence of different kinds of allergies and asthma is a lot lower as opposed to children raised in an urban area. Similarly, in the developed countries, developed regions of the of a third of the world. They also see a lot more cases of allergies and asthma and other related hypersensitivity actions. As opposed to less developed or underdeveloped countries. So it's believed that. If it if we are not exposed as in our childhood, if we're not exposed to all these different kinds of microbes or parasitic worms, the less exposure will make us make our immune system less tolerant of any antigen that ordinarily should not cause any unneeded reaction. But in in those people, it does. So it is, in other words, large immune tolerance. And so something that should be a harmless antigen, it provokes asthmatic reaction or other types of allergies. Something else is also that in these developed countries, they also are seeing more and more
harmful bacteria, such as Clostridium difficile, which I'm sure you've all heard of, a city that is a big problem these days in the hospitals that infects the GI tract. And they're seeing more and more prevalent incidence of this. And they also attribute that similarly to those antibiotics that are available. And in more, you know, developed countries, different kinds of antibodies that are available. But the these antibodies also cause an imbalance of our normal microbiota. That imbalance is called displaces so that then they believe that is a reason for having Clostridium difficile infection. Why? Because those little more microbiota in our GI tract, they also produce different antiinflammatory substances that are called butta rates. And with normal microbiota gone because of extended amount of antibiotics, therefore no rates. And therefore, as organisms such as Clostridium difficile takes over because of infection and also the disposes is considered to be responsible for inflammatory bowel disease, that bowel disease that is also very common disease. We're seeing more and more of cases of inflammatory bowel disease such as. Before I go to next slide, let me talk about. This is actually Clostridium difficile and you're looking at the spores and rod shaped bacteria, and for one of the one of the treatments that now they use for treating Clostridium difficile infection is using what they call poop pills, which is also called fecal transplant. And what they get these from these are actually the microbiome of healthy individuals which are placed in these. They're covered with three layers of gel so that, you know, in the stomach, they will not break down once they're exposed to acidic environment of the stomach. And so they're hoping that this way, normal microbiota will be introduced back into the GI tract of individuals who have been have been
undergoing long treatment, long time treatment of antibiotics, and therefore now they're infected with Clostridium difficile. So in order to replace the last normal microbiota of the GI tract, they are using fecal transplant this way. So. So, as I was mentioning earlier, inflammatory bowel diseases are some of the outcomes of display ulcers. So there are two of them ulcerative colitis and Crohn's disease. And I'm sure you've heard of those because they're becoming more and more prevalent, both of them. What is happening is chronic inflammation and alteration of GI tract, specifically colon and rectum. If it's ulcerative colitis and we're looking at an ulcerated colon and how it looks compared to a normal colon. And for a case of Crohn's disease, one thing that they are has has shown some remission of people who suffer from Crohn's disease is using ingesting whipworm eggs. So this is a whipworm. And so those eggs are used as a treatment. And the reason for it is because they are known to actually depress or helper T cells. And so eventually they're going to depress cytotoxic T cells. And so what is causing the alteration is cytokines, such as tumor necrosis, factor alpha that we have talked about the previous chapter and also one of those interleukins is interleukin 12. These are specifically associated by food associated with the these ulceration.
All right, so now we're going to talk about hypersensitivity. Is exaggerated immune response. They're divided into four groups and we're going to talk about to start talking about type one, which is known as anaphylactic, and notice that the reaction,
obvious signs of this type of hypersensitivity actually takes place within two to 30 minutes is always less than 30 minutes is closer to like two to you know, we're closer to two minutes rather than 30 minutes. It happens very quickly because I have seen it up close and personally when it happened to my son. Within minutes, you can see reaction. So notice that our eyes are
the involved here. If you remember from the previous chapter, you know that IGs are involved with allergic reactions. So bugs bind to muscles or basal fields and they cause the granulation and what is in the granules histamine in addition to other types of chemicals. But the major one is histamine. And you remember from the one we are talking about inflammation in in the in Chapter 16, that once histamine is produced, that is going to cause vasodilation, fluid rush into the area and and also the swelling edema. Those are associated so less with this. So let's look at the graduation process here. So here is a muscle and you're looking at as a result of OGX binding to them. Notice how the granules are then released and what's in the granules, the major
chemical that is responsible for this. The the reactions are going to follow the major chemical necessary. So these are histamine is in their leukotrienes uncrossable, and they're not in these granules. These are actually produced by cells that other cells that have been affected. And so the combination has achieved a toxic effect, which means that is going to attract neutrophils which are difficult to take to the area. And they have enzymes. Those enzymes, once they are released, they can attract other types of cells, such as eosinophils, which you remember. These are involved in parasitic infections, but also once basal fields are already or Marseille's have already released histamine, eosinophilic are also attracted there. And there are two types of anaphylactic reactions, one that is localized and the other one is systemic. So obviously localized is a localized reaction, an immune reaction. Systemic involves the whole body. So we're going to talk about examples of localized. So first, these two are examples of localized respiratory reaction as opposed to localize skin reaction. So what both of these or all three of these are localized anaphylactic reaction. So is involved in all of them. Obviously, as we mentioned before, hay fever is a localized reaction of the upper respiratory system, whereas asthma is a localized reaction of lower respiratory system. Right. And again, that anything that can be allergic can can provoke this, such as pollen, fungus force, dust mites, not dust mite itself, but it's actually dust mite feces that is causing this stress can cause asthmatic reaction in some people, isn't it? So anything that can cause hay fever is some people can cause asthmatic attack. But hay fever involves the upper respiratory system as more involves the lower respiratory system and the solve the crisis of hay fever depending on the person. It could be teary eyes, you know, watery eyes. It may be coughing, sneezing.
Everything that we consider with something like hay fever, some allergic reaction might increase mucus production. Asthma is lower respiratory. This is where you have the that can be more severe, can even be fatal. Right, if medications are not available. Because in an asthmatic attack, what is happening is that the smooth muscles of the bronchial tubes, those are constricted. And that can that's where the people person might actually experience shortness of breath, laziness, and which can be actually dangerous. So even for you might even know if you've got yourself, you might know someone who has asthma. And as I mentioned before, in developed countries, we're seeing more and more of these kinds of allergic reactions. So one of those inhalers that is used is called albuterol. You might be the one using it or know someone who is using it, but what are they doing? They're bronchodilators, meaning that they are causing their dilating those bronchial tubes. You know, the same ones that I said, would it constrict as a result of this as opposed to Zulia? You know, the arbitral is a brand name. So so there is a brand name also, and that is a blocker. So meaning that it will prevent algae's from binding to muscles or basal fields because it all it all starts with this. Right, with binding of these onto a muscle and therefore the granulation follows. So those are ECG blockers and then we have Singulair and those are Leukotrienes blockers. So if you remember, not only we have histamine involved, but we also have Leukotrienes involved. So those are the ones Leukotrienes are actually the ones that cause also increase the cause constriction of those muscles of bronchial tube as well. And the process of landing is also produce that causes increased mucus production. And so Leukotrienes blockers, you can see that, that those will be very important also in helping an asthmatic, someone with the asthmatic attack. Both Zulia and Singulair, also used for Hype's and Hive's is what you see here, which is just slightly raised skin person's skin that is also itchy. These are always in reaction to an antigen that is ingested that causes hights. So ingestion of something that you might never know what it was that caused allergic reaction and might not happen again. But when it happens, it's unpleasant, is itchy. It lasts maybe a couple of days and then it's gone. But then there is relief. Both Zulia and Singer help with this skin reaction. So this is just a skin reaction. It is localized, but these two are respiratory reactions still localized or all are localized. These two, however, there is also a systemic anaphylactic reaction. The systemic anaphylactic reaction is also called anaphylactic shock. Shock is severe and sudden drop in blood pressure. And why would that happen? Because the people who show an exaggerated immune response to an antigen that has been ingested or have been inhaled or it has introduced the via injection such as venom of insects. And so what happens is that, again, over a simulation of the immune system, which starts with, again, histamine production, which causes vasodilation, but this is not local anymore throughout the body. And so you would see the the swelling, as you can see on this child and over here. And also because of the increased permeability of the blood vessels, fluid leaves blood and rushes into the area and that causes edema. But that fluid would leave the blood vessels that cause a sudden drop in blood pressure that. That's the reason for that survey collapse in the. Which is those people who know that what they're allergic to and I'm not just talking about any outrageous reaction, I'm talking about anaphylactic shock, which is systemic. Some people are sure that for the reaction to peanuts or other peanuts, some show those kind of reaction to these things, specifically what, even penicillin. So those who do know that they have they are aware of this. And I think shock response that they could have to these kind of allergies, they should be carrying EpiPen with themselves. And so what's in their. In EpiPen is epinephrine and the reason for that, because you want to constrict the blood vessels again, you know, epinephrine were constrict the blood vessels again, so prevent loss of fluid from the blood vessels. So it's opposite vessel dilation also. So that's what's in the EpiPen that those people should be carrying. People actually have died from not having an EpiPen. If you are aware that you have this kind of reaction to anything, that that's something they should be carrying.
For some of those, such as antigens that are inhaled or if they are introduced into the body by injection, such as insect, again, for those, what is more what can be done is called desensitisation. The synthesis sensitisation is that what they do is that gradually they introduce more and more higher and higher dosage of that antigen when they know what that person is, you know, I object to. So gradually they increase the dosage and introduce that into beneath the skin and introduce into the body. So when they do this, what is happening is that they're hoping that Eigg, the immune system, will produce Eigg in response to the controlled doses of those antigens that are introduced into the body. And Insadong before Eigg is for use. Because if you remember the exact problem, that's the one that binds the muscles and the soldiers and that problem starts there. But was ECG is produced before the body has a chance to make those images block the antigen. OK, so that's that's the reason for. That's the. That's the.
Principle behind this and again, is more effective when it's an antigen that is inhaled or in cases of insect venom which are that are injected. This is just showing you a skin test that in order to find out what your energy to look for some of those energies, this this can be done, which what is happening is that these are most common allergens that are introduced by, you know, the fluids of each one of those antigens dropped is placed on the skin and then just a little scratch with a needle. Then the antigen will penetrate and goes below the skin. And so if there is an allergic reaction, then you can see it. That's how they find out what what's your age of two?
So. So far, we've been talking about type one, the next one is type two allergic reactions, which are known outside to toxic reactions, cytotoxic reactions, and noticed that in these LGM or IGG antibodies involved. So once the antigen is introduced into the body, either one of those will respond, they bind and that will activate complement proteins and also macrophages, which they produce these enzymes and all of them together. They break down that cell until the cell reaction, the damage, I should say, to the cells that don't affect that would actually show up in 48 hours. So examples, transfusion reactions you have done before. We were talking about antibodies that are involved with reactions to incompatible blood type, if you remember. So you can see that they are involved here. So anything that has to do with the Orridge antigens and the Avio antigens that are on the surface of red blood cells. So if you look at this table, it just reminds you of, you know, the different blood groups and also what that means when someone has that blood group with antigens they have and what antibodies they do. So I'll let you read through this to remind yourself. Noticed that in us. Most people. Or have type? Well, I should say a white
ethnicity in a U.S. population, 47 percent. So mostly they're all similarly with.
Yeah, 47 percent, though, and then similarly, the African-American 49 percent and Asian 40 percent type, or
the blood group, a blood group. If you take a look here, you can see that car, not Stainer is or Seiter is responsible, is the one credited with and actually got a Nobel Prize for his discovery of the AB or Antigens and blood group. And then and then with cooperation with Alexander Weiner, they identify the RH factor. And if you look at it, this is not too long ago. This is 1937. So
nobody knew of that before. And also, Dr. Charles Drew is the one, the very first person who actually developed the very first blood bank,
which does amazing job throughout the world. And then this also lets you read through it. And you can see that depending on the year, it's not just a blood type with a but also the Orridge is important for, you know, who can receive blood and who can donate to blood types without being rejected. Otherwise it'll be rejected. Right. So IGM, Ogie and. In case of hypersensitivity, reactions and compliments are involved, however, you've learned that Egham is a type of antibody, that response to a blood type that takes us to hemolytic disease of the newborn.
And that is when a woman who is orosz negative carries a child who is Orridge RH positive. In first pregnancy, and so she does not have a. Orridge antibodies, but she will make A.R.T. antibodies during delivery where the transposon, where the placenta, our memories break. And so therefore, some of those blood cells are going to mix in with mom's circulation. They're going to enter in circulation. And so that's what she's exposed. And she's going to make a.. Orridge a. a. orridge antibodies. But she doesn't have other Orridge until then. Or if it's a trauma, you know, during the pregnancy, where would lead to the mixing of the moms and the child, the fetus blood. So if that's the case.
Twenty eight weeks of pregnancy or soon after delivery then or unless there's a trauma before. So that's when drug is given to the woman, Rogan. It contains a.. Orridge antibodies. It has Antigonish antibodies. So it was going to prevent Mom from making antibodies, antibodies. And is why? Because it's going to these antibodies are going to, given that time, are going to neutralize any RH positive that might have been introduced into mom's circulation. They're going to bind them, neutralize them before mom's immune system has a chance to make antibodies against. In any case, the first pregnancy, the baby would be fine. But it would be the of the subsequent pregnancy, if it's with another positive RH positive baby, that's when there's a problem because she already has antibodies against RH positive against Orit antibodies, excuse me, I guess Orridge antigen. And so therefore, there are these antibodies already circulating in her blood. And this is another RH positive
fetus. And so these antibodies cross placenta and they will destroy the baby's red blood cells. So the fetus is going to make more red blood cells, which are going to be immature red blood cells, because it's just going to increase more to compensate. And those broken down red blood cells are also removed from the fetus's system by the woman's.
Enthusiasm, however, once the baby is born, then that cleaning up is gone, so therefore that newborn is going to have developed jaundice or anemia and a blood transfusion is usually what is done in those cases. And so so that is called hemolytic disease of the newborn. And this is the only scenario where this can happen only if the woman is Orridge negative and the child that she's carrying out is positive and the subsequent pregnancy is also another RH positive.
Fetus. All right, so.
With Type one and type two. Type three is called immune complex. And so let's look look at five three immune complex reaction the immune complex is talking about is one antigen antibodies bind one another. That's called a complex. This only happens when there's a certain ratio of antigen to antibody with a slightly higher. Molecules of antigens and in those cases, these complexes form and they are deposited in a base membrane of you can see this blood vessel. These antibodies are already formed and that will attract complement proteins, we've already learned how complement proteins can damage have a damaging effect on the cell. Neutrophils are also attracted and neutrophils are enzymes. So more damaging of the tissue, as you can see here, the endothelial cells lining this blood vessel there, they're being damaged. But as alternative fuels and by compliment, notice that they're not showing you the ocean, you know, that's. So compromise will be also attractive. So the reaction can be seen in as little as two to eight hours. Two examples of immune complex reactions. One is from sickness. So serious sickness happens in some cases when foreign antibodies are given to an individual by foreign antibodies. If you remember from. I believe it was last chapter when we talked about how antibodies can be given to an individual, antibodies against the pathogen can be given to an individual to confer temporary or temporary immunity to that pathogen. That's what I'm talking about, is some people, the recipient of those antibodies are actually going immune system is going to show an immune complex reaction, and that is going to lead to destruction of the endothelial lining of whatever that those blood vessels are affected. For example, it could be in the club, if you like, of kidneys in case of artist reaction. So this immune complex is actually going to be deposited in the blood vessels in the grumbly of the kidneys. And that's how
those are damaged, which is going to affect the kidneys. So that only happens in case of. Vaccinations that have inactivated toxins or use as vaccine inactivated toxin inactivate toxins called toxoid. So in some people, those type of vaccines induce a hypersensitive reaction known as immune reaction. So when is a toxoid that is doing this? This is called Arthus. Reaction after reaction often leads to glomerulonephritis. So that's when it's the right of a kidney. So that affected.
Type four is called cell mediated or delayed hypersensitivity reaction. The reason is called delayed hypersensitivity because it's T cells that is involved here. So far, the ones we've been talking about were they were all antibodies involved. You know, antibodies were involved and then compliments were activated or then followed by neutral. Right. But here it's it's t cells. He's also removed so example's allergy contact dermatitis like people who are allergic to latex gloves, for example. The same substance that can be found in catheters, some people are ready for that. And so what is happening is that these people have been introduced to that antigen before. So they have the first sign that they're introduced to that antigen. That immune system is not showing a massive reaction, but that's just called sensitization. So what happens is that the first time that they are exposed to that antigen, their immune system is so sensitized. That means that they're exposed, they've made memory t cells because of the first exposure. Once they're exposed to it the second time around, that's when they already have those memory t cells and they're going to launch a massive destructive reaction. And that's what you're seeing in this destruction of the skin cells. In this case, that's that's what I did contact him. Titus, this is the same. Principle is the same principle behind the TB test because with TB tests, which I'm sure I'm sure all of us have done it at least once, is this that what they do is they introduce a controlled amount of the antigen, not the whole bacterium, but the antigen on Mycobacterium tuberculosis beneath the skin. And then they look for, you know, what or two days afterwards is delayed. Right. It's not immediate. They look for an inflammatory response. So where when would there be an inflammatory response? Only if that individual has been exposed to that same antigen before. So meaning if the person has is infected. Or was infected once upon a time in the past, and and so that's how they would already have the memory t cells and then then they would show up like this and skin reaction that they would be able to see as a personal reaction. That means that they haven't been exposed to that antigen before. So this is another example of alleged contact and mutatis, which is about poison ivy. Poison ivy has a substance called cortical Kathakali itself. Is Hopton meaning that it cannot induce an immune response? However, when it mixes with skin protein called ricin, then it becomes antigenic. And in some people they develop immune response exaggeratedly immune response the second time around there, alleging they're exposed to it. So not the primary, but the second type sensitization in all of these allergic reactions that we've been talking about says that the physician is when you've just formed the memory cells. So in this case, t cells are involved. So it's memory t cells. Once you're exposed to it again, that's when your your immune system is going to show an exaggerated immune response that is destructive to the tissue. In this case, a skinny ship. Autoimmune diseases, autoimmune diseases, as I mentioned earlier, occur when our immune system cannot. Distinguish between self versus non self tissue and organs. And all those components of the immune system that are meant to get rid of a pathogen or anything that is non self or is against the abnormal cells, those are produced against our own tissue and organs, and that's why they still nevertheless, they have destructive effect. And here are some of the awesome businesses that are listed in this table and we are going to talk about. Some of them. So let me start with Graves disease, Graves disease, which what happens is here antibodies are involved. So what is taking place is that the on on our thyroid gland, thyroid gland, which would be over here,
there are receptors for thyroid stimulating hormone that is produced by our pituitary gland. So our pituitary gland produces thyroid stimulating hormone. And then those hormones were bind to the receptors on the thyroid gland. I'm talking about normal situation and then the thyroid gland will be similar to produce thyroid hormone. Right. But what is happening here is that antibodies is that are binding those thyroid stimulating hormone receptors on the thyroid gland. And so the plan doesn't know the difference. Is going to respond by making thyroid hormones when it's actually our body that's needed, direction is not coming from the pituitary gland in the brain. The direction is is coming from our abnormal reaction of our immune system, which is making antibodies that are going to bind to those receptors on the thyroid gland. Nevertheless, that will and cause hyperthyroidism increase production of thyroid hormone. And that's also known as goitre, which is usually shown up as it shows up as a large and disfiguring.
Thyroid gland, what you can see, the neck is enlarged, also bulging eyeballs, you know, as if they're staring at you, which they are not. And so those are some of the things that you can see when some people who have the excessive, you know, they have not they're not treated. And also but aside from that, that causes
abnormal increased heart rate and pounding heart late night sweats. And also it has to be treated with controlling the amount of thyroid hormone that is excessive in them. So by periodically testing them and they have to be controlled. And then next is myasthenia gravis, which is another autoimmune disease. And this time what is happening is that we're just not like the normal
physiology and anatomy of this, where you have the nerve endings and you have the membrane of muscle cells. And so from the nerve endings of the neuromuscular junction, you have these acetylcholine, right, as you call a neurotransmitter that's produced at the nerve endings producing to the junction release into the junction. And they're supposed to bind the receptors on the muscle cell membrane. That's how the nerve that's all communication is happening. Right. That's how the muscle tissue is receiving communications from our central nervous system, for example, to contract. Right. So what is happening here is that antibodies are produced that are going to instead bind those receptors, therefore blocking the receptors. And so therefore, acetylcholine cannot find those receptors. Because they're there, they're blocked by these activities, so meaning that there is no communication going on anymore, so that eventually is going to cause the weakening of those muscle tissue. So when it's the diaphragm or Muslims that are involved with breathing the picture, our muscles that this is happening to the outcome would be what, respiratory failure? So and that follows. So this is called this is another immune autoimmune disease, and the next one that you might have heard of as lupus is the name is really systemic, lupus, lupus, a tomato sauce, because it's multiple organs that are involved, including the heart. Kidneys are involved. And so what is happening here is the immune complexes, that antigen antibody that I talked about earlier, those. This should be deposit, that should be not a deposit in the kidney community, and so they cause kidney failure because of those glummer you are going to be the blood vessels in there are going to be affected. And so one of the earliest one of the things that when a physician looks at the patient, they can tell right away that this is the start of lupus is a butterfly rash on the skin, not like this. You can see how this this is really
the cells are destroyed here, but it might not be this severe when just a slight, you know. Reddening, but it's always that butterfly shape on the face that tells you that's a sign that this is lupus that the person is suffering from. So in this case, antibodies are actually produced against cellular components, including against the innate. Because DNA itself and you can see how damaging that can be.
Rheumatoid arthritis, again, is immune complexes, again, antibody antigens, the antibodies in both urology and idea, and once those immune complexes are formed, they're deposited in the joints, usually starts with the small joints like toes and also fingers and what they're deposited, they're going to activate compliments. And they also have seen that these are the same
the same types that are produced against the strip to caucus antigen. So that, you know, for all of these autoimmune diseases, they really don't know what what is the causative agent? But for some of them, they they think that there is some association with in this case, with this bacteria. And a case of Ms. Sure, I'm going to talk about later, they think is of similar size. So, again, they don't know what really causes any of these autoimmune diseases. They just see that, you know, what is what why is the body producing these harmful substances against its own tissue and organs? But here, these bacteria might be involved because they see that are the antigens antibodies that don't produce or against strep antigens. And they're also depositing joins because of the activation of common proteins, the joints, the cartilage, the joints and even the bone in severe cases are destroyed, affected and and would be crippling the GM, the two of them behind one another in 70 percent of the cases. They can actually when they test the person they can they can see this so that this IJM hoggy together is called rheumatoid factors, say 70 percent. Not everyone, but 70 percent of the cases of rheumatoid factors are rheumatoid arthritis patients. They actually have these factors circulating in their blood.
Insulin dependent diabetes mellitus. We're looking at the same child, by the way, before treatment and after treatment. So what is going on here is that the body is producing. Cytotoxic T cells, C not not antibodies, cytotoxic T cells against the pancreatic cells that produce insulin, so it destroys the pancreatic cells that produce insulin. So basically a child, even though is is being fed but is dying of malnutrition.
And so before insolently.
Treatment and after treatment is cytotoxic, t cells that are attacking and destroying the pancreatic. So that produces multiple sclerosis or MS also cytotoxic T cells are involved that attack the myelin sheath of nerves. You know, that nerve, the axons have morishita on them, which help them. White sheets are responsible for speed. They speed up the rate of transmission of neurotransmitters, right. So if something is destroyed in my Rashied, which T cells are destroying the wiring sheath? A basically then the neurotransmitters cannot effectively and in a timely manner be passed on to the corresponding muscles, so so that starts with feeling weak, but eventually paralysis where they have to use a wheelchair and some even the muscles in the eyes are affected and they become blind. And so this is a progressive inflammatory disease, starting with t cells attacking, but also that macrophages follow antibody swallow.
So that's another so far, although of the activities that we talked about, insulin dependent is where T cells are involved. Multiple sclerosis is T cells are removed. And then same thing with Hashimoto's thyroiditis, which is opposite graves' disease. This one, hypothyroidism is the outcome, meaning decrease the amount of thyroid hormone here. Also T cells are involved. Cytotoxic T cells actively attack the thyroid gland and so therefore
reducing the amount of thyroid hormone that is being produced. So and in patients that are suffering from Hashimoto's, they have the experience, reduced heart rates, reduced metabolic rate, hair loss, feeling cold. And they and the thyroid gland, sometimes in severe cases when it cannot be controlled, what they do is that they remove the whole thyroid gland.
And then, of course, the patient has to be, you know. For their entire life, they have to be receiving and adjusting the amount of time to. Psoriasis and 25 percent of people who develop psoriasis also develops right psoriatic arthritis, and again, such a toxic T cells are responsible for it. They attack the skin cells, causing these red, white, scaly patches on the skin. Usually it's on the elbow. And thus, because of these talks, cyto toxic T cells, chemical that they produce, they also promote the growth of keratin cells that produce keratin here. So Kratom sites, critical sites which also produce kidney to make more. I have seen pictures that are not you know, this is not bad, just a surgeon. I will show you all sorts of carotenoids skin because of that. Oftentimes corticosteroids are used. These are, of course, affright antiinflammatory. Same thing with rheumatoid arthritis. Also corticoid or corticosteroids, which are a series. They're used. There are other inflammatory.
And so we talked about also, you know, diseases which are unwanted, there are unwanted overreaction or immune system or immune system is basically malfunctioning. Another Ferriero immune system. When Kasit happens. The immune immune surveillance has failed.
Ordinarily, cancer cells are destroyed by a or immune system such as dendritic cells. You know, as I mentioned earlier, they can identify these antigens that are
that are not normal on cells that are cancer cells. So they are displayed there and so they can identify them, they can attack them. Same thing with, as you know, our cell mediated immunity attacks, cancer cells. It's actually thought it also to cells in there that attack cancer cells. Macrophages, which are also involved with or even the first line of defense, they're phagocytes, they also attack cancer cells. So all of these are failing when someone develops cancer.
Because there are some reasons because these cancer cells, they make more of themselves so quickly that they think that what's happening, that the immune system cannot effectively respond. Quickly.
And also that there are no antigenic epitopes, you know how you know how and pathogen's, for example, you have these antigenic epitopes people is going to.
The cancer cells don't have that. So that's why they don't have those epitopes for antibodies to go into but cytotoxic T cells. Which are these?
Are the major players here to chill these abnormal cells and also dendritic cells? I mean, natural connoisseurs of steroid safe cytotoxic T cells, natural causes, they're really the first ones that attack cancer cells. So it's the failure of our immune system, so some of the. Approaches, treatments or treats? By Sarah endotoxins, which first. Decades ago, Dr. Coley found out accidentally that these bacterial toxins that are specifically endotoxins that were involved, he noticed that they actually reduce the cancer cells. And that's then then they was discovered that the way they do it is that these endotoxins actually interfere with the.
Vascularization of those cancer cells, so meaning they to feel with the blood supply, so the blood supply is there, cutting blood supply to these cancer. So that's how that effective. And then, of course, we have some of the vaccines that are developed now, those are prophylactic, meaning that preventing cancer. This is what someone already has a cancer. This is how do we prevent it? Well, if you do know that some forms of cancer, such as we've talked about hepatitis A, hepatitis C or subeditors, which is responsible for liver cancer, but also papilloma human papillomavirus, which is associated with cervical throat anymore cancer. So these are already known. So then they have vaccine now that are given to people, everyone to prevent this type of cancers from happening. That's called prophylactic. Right. And then there's also there are also these monoclonal antibodies. So monoclonal antibodies are very interesting. These are not these antibodies are not knew how to make. These is not you. I remember how many years ago, a few decades ago, where actually I was working in biotech, a pharmaceutical company where actually we were developing monoclonal antibodies to be used for pregnancy test kits, you know, the same kits that is all over the place now where can get what they were ordered and also for thyroid deficiency. For a SREP, if it's a strip pugilists test for strep throat. These are the three kids that actually, you know, over the counter kids.
For pregnancy and the other two in doctor's office that I also was working on it decades ago, we were using monoclonal antibodies. So that's what I'm saying, that this is a development. Monoclonal antibodies is not new, but what is used for now, those are newly developed. For example, what's the you know, the brand name is called Herceptin that is used for breast cancer, for example. This is used for leukemia. Right. So another cancer, cancer with blood cells. And then they have they've developed multiple antibodies that then they they combine certain toxins to it. And then those antibodies are against these cancer cells, Hodgkin's lymphoma. And so when they are introduced to the body, those antibodies find those cells. And because they already have tuks toxins attached to it, the idea is to cure those cancer cells. Similar similar thing, except that these monoclonal antibodies have radiation attached to it. So once they look for those cancer cells, they're going to kill the. These are new ways of using these monoclonal antibodies, so you need to memorize these names were immuno toxin is not a brand new neurotoxin means these are monoclonal antibodies in this case against these cancer cells. And they just combine toxin with something else. This is not a brand, but these two are. So you don't need to memorize the names. But you should know that there are these monoclonal antibodies for these forms of cancer. If you're interested to know how they make monoclonal antibodies. And the names that are there are missing. I don't have those names here, but any name that in the medication, if the name ends with, may be at the end, meaning that it's a monoclonal antibody. So all of those letters that come before that, maybe they are referring to whether or not those antibodies are fully human antibodies or are they from mice or are they a mixture of components of mice and human antibodies, which is sixty six percent. That's what the Z is telling you, the ACLU versus humanised, which is 91 percent. So I'm not going to explain all of those. And I do not require you to memorize these and what each means. I just have them here so that those of your interest could go ahead and look at this. This is in Chapter 18. That's how they make these monoclonal antibodies. That's what I've made these monoclonal antibodies actually in the lab for pregnancy test. So interesting is very interesting and more exciting that they are developing these against these different forms of cancer immunotherapy for cancer, using antibodies against cancer cells.
All right, so some cancers depress the immune system.
And cause immune deficiency. There are different forms of immune deficiencies, those are congenital, also known as primary meaning. This is some that form of immune deficiency that person is born with as opposed to a quiet. And that's called second degree. So, again, the acquired could be artificially acquired or naturally acquired. So I talk about that later, but this talk about congenital versus the form of immune deficiency immune system is not functioning normally because of some genetic issues. Right. One is called de jure syndrome, also known as CIMIC dysplasia, where because of abnormal absence of this gene or or abnormal gene, there is no time. Escala. That the developing fetus never develops the thymus club. So if there is not time to think about it, there is no cell mediated immunity because certainly this immunity is the one that T cells are removed, t cells are maturing in thymus glands, so they don't have that component. And those who were babies were born with that condition, a genetic this disease that they're born with, they also have or similar characteristics as far as their facial features are considered, because the same gene that's defective gene is also responsible, giving them this similar facial characteristics. So now time is usually that is fatal in childhood. OK, severe combined immune deficiency. That's the one that we talked about before. Severe combined immune deficiency will be recovering, I believe, chapter. Night.
Technology, you've seen the same picture before, and so what's happening in these children, they're born with no immune system at all. So all companies are immune systems are missing. So both of these are examples of congenital. And so for this, they use fetal timea transplant, bone marrow transplant, right? And then, of course, gene therapy. That's what we talked about before. Such as hers was a successful case acquired or secondary immune deficiency, natural artificial is when a immunosuppressive drugs are administered in order to depress the immune system, for example, in cases of people receiving transplanted tissues or even when they are, they are showing severe destructive allergic reaction. For example, severe psoriasis. Those are also given immunosuppressive drugs. So they do the same thing. They depress the immune system. So I'm going to talk about some of those drugs, natural acquired immune deficiency. Well, HIV, right, HIV. The virus that primarily infects the Hilferty so t cells, but it also affects the macrophages and the writing cells. Cancer, some cancers such as Hodgkin's lymphoma, which actually paralyzes the cell mediated immunity, the T cells, if you remove a splint for any reason from a person that will cause antibody mediated immunity, lack of antibody mediated immunity. Right. Because that's where Vsevolod evolved. So these cells are loaded with B cells and that's where you would find them, many of them. And so no spleen cells? No. Or reduced much reduced antibody mediated immunity. The reason I have the picture of this Nordmark my mouse is this that no mouse the mouse because they don't have here so mouse without her. This is why it looks even more scary.
Why was it that they don't have here, well, they're born this way because they're their immune systems, they don't have the gene that is involved with. Not having thymus gland is also bald with no hair, so that defective gene results in the absence of thymus gland and axis of hair. So these mice actually are used in immunology research labs, cancer research labs.
For, you know, all sorts of reasons where they need that specimen to have no cell mediated immunity and they're used for, for example, they're also used for transplant studies, as you know, transplant that organs are or or tissues are attacked by such doctors. And so.
For those kinds of studies, they need these animals that do not have time. And that's what they're used for.
Transplantation, which again, is cytotoxic t cells that detect attack and kill. Transplanted organs, cells and through the organ.
But there are. People who receive corneal transplant is so common. It's really, really rejected.
By the recipient, corneal transplant is rarely rejected for that reason. This is called a immunologically privileged site. And they think that's because there are no blood vessels in the cornea. Brain is also called immunologically privileged life, and that's because of blood brain barrier, the blood vessels there are impaired in.
Or they won't let anything enter the blood vessel. Pig heart valve transplants also are known as privileged tissue, immunological privileged tissue. This one, and if someone receives a pig heart valve transplant for a faulty heart valve, it's not rejected. And. And that's only after they actually get rid of some of the components of the cells and then that's a privileged tissue, so meaning that the immune system is not going to do that is not going to attack it.
And. And then how about the bone marrow transplant, right? We know that that that is, for example, in case of. Before gene therapy, they tried out for David Smith. They talked about earlier in the province, one of the previous lectures where he received he had severe combined immune deficiency, but then he received one transplant from his sister, but he developed cancer and died. Well, some some people, after receiving a bone marrow transplant, not for the same reason he developed cancer, but they can have some other difficulties called graft versus host disease. So if someone doesn't have a healthy immune system for whatever reason, and then they are given a bone marrow transplant, which is also known as hematopoietic, meaning that these are, you know, what do we have in bone marrow? We have stem cells that are producing blood cells. Right. So that's what it's called, hematopoietic. So some people, when they receive this transplant, because they don't have immune system themselves, they're hoping to be able to have a healthy immune system after receiving this transplant. But what happens instead is that the components of those stem cells, which are. White blood cells, right, that are part of our immune system, those will attack the recipient's. A tissue. So that's called graft versus host. The transplanted bone marrow is attacking the recipient's. Tissue and the recipient doesn't have an immune system that's is receiving a transplant. Bone marrow transplant, so this is what that's called. So that's an issue that can develop. And so grafts, which are different types, depending on where those tissues are coming from, for example, autocrat's are tissue transplants from one region of the body to another, but another region of the same person.
But also what they do recently is that, for example, they want to do skin graft, right? And so what they do is that they actually grow. This is personalized medicine right across the cell, the skin cell of that same individual in the lab. They make it tissue and then they use it as a graft. And, of course, it will not be rejected because this is the person's own. Onsets. It's not not self, so it's not going to be rejected either, graft is between.
Between it's the graft between identical twins, identical twins. So, again, would that be rejected? No, because identical twins, identical genes. And so therefore, they will not be recognized as self allograft Hallmark or Graff's between any any two individuals other than identical twins. So in any two individuals, so obviously the more closely, you know, blood related they are, those two individuals, the donor recipient, the better chance of that graft not being rejected. And then there is xenograft. Or xenotransplantation, so tissue or organ that is received from an animal. Right. So that.
As you can, as you know, these are completely for it, because they're not they're not even human.
Tissues and organs, so
hyper acute rejection that can happen is this is that during infancy, humans leave their bodies for antibodies against any antigen that is animals. They. And so if they are exposed to it, they're going to show a hyper IQ, rejecting it, rejecting those that are antigens of their non-human. So if that's overcome, then there's a higher chance. So although of all of these.
The least
problematic, of course, is autograph. Isaac, left, right. Both of them, but the worst and the highest chance of rejection, of course, is xenograft because these are tissues from Iowa and that's word that if you remember, when we talk about monoclonal antibodies, which said, you know, like 66 percent, 90 percent humanised, that's where that comes from. There's a lot of research now because of the fact that they would like to be able to use, you know, animal heart or or tissues, if not the organs. For transplant, because people, as you know, they they wait, they're waiting for these transplants and they don't want Righi, and it's not like we have storage of these organs for them to use. So that's what they're looking at. How do we humanize these meaning that have antigens there, replace the antigens of humans in a way that they will not be rejected? And and, of course, for right now, for anyone who receives transplants.
Transplanted organs and tissues, they need immunosuppressive drugs. We're not talking about these exceptions, and there are basically two types of immunosuppressive drugs. One of the older ones cyclosporin, which is was originally isolated from cyclosporin, which is a fungus. And then.
Taxonomists and basaltic Seamap. As you can see, this is monoclonal antibody. So these are they depress all of these, depress the cell mediated immunity. Remember, certainly the immunity, the one you want is the branch of your immunity that you want to. Prevent from functioning because that's the branch that attacks transplanted tissues and organs, so they are immediately used in a patient who has received the transplant and Saralyn, US and Michael Fennell, eight, those are used. Those are not only the press, the cell mediated immunity, but also antibody mediated. So when is it that they would use this? Well, you know, as I mentioned initially, this was used because you want to depress the cell together, the immunity. These are used only when they see, you know, after what they see in evidence, the evidence of formation of anti antibodies, antigen immune complexes deposited in the blood vessels. And whose antigens are those? The donor's antigen. Right. For example, it's a heart transplant. So those antigens are the belong to the donor who has the heart is coming from that individual. So the person is forming antibodies against those antigens. And so those are being deposited in the blood vessels and eventually blocking the blood vessels. You would have the same effect as a plaque would have in the blood vessel, except, you know, it's still going to block the blood vessels, but it's not for the same reason. So that's when they have to use this, because now they want to slow that down also. So we still want to depress the T cells. But you also I mean, with with these but these Duboc now you need to depress the antibodies also. And as you know, immunosuppressive drugs, people who are taking these and they need to be taking these for the rest of their lives, then they're more prone to developing cancer. Right. Because you're depressing their immune system. And more prone to develop infection.
All right. We've talked about his compatibility complex molecules, right? So histocompatibility antigens, those are the molecules that are found on the surface of our cells, of our body. Those are the ones that are self versus non self. Right.
There are genes that code for those, there are multiple genes and there are multiple alliance forces that code for these antigens. So those genes are called the major histocompatibility complex. Those are the genes. In humans, these antigens are also called HLA, which is
called the abbreviations for human leukocyte antigen. So if it's a complex meeting that you refer to. So these are the major issues of compatibility, complex genes in humans. So they're called humans. They can also be called actually OK, which is what, actually typing then then you might have heard of becomes important because in cases of transplantation, not only they should think about the recipients of the donor's compatibility as far as the blood, the ABO and Orridge compatibility blood group, but also they have to do HLA type. They should match to and to prevent rejection by the immune system. And so notice that also having certain types of Italy in people increases the risk of some autoimmune diseases like multiple sclerosis, rheumatic fever, which is a complication of strep throat or aspergillus infection. Addison's disease, Grave's Disease. We talked about Hodgkin's lymphoma. I just mentioned the name, but which is cancer of live nodes. But notice how. In in certain certain areas, there are different causes to make people more like five times, it says, more prone to develop M.S.. You know, or, you know, like about two times more prone to develop this kind of cancer cell, 10 to 12 times more prone to develop graves disease that we talked about. Of course, I don't need you to memorize these numbers, but I just want to emphasize here that the HMAS. Uh. That are unique to each individual, that we inherit them right from our parents and so. The type also certain types are also associated with higher risk of developing certain types of cancer or even autoimmune diseases. And so we were talking about natural versus artificial acquired immune deficiency. We we talked about, you know, before we talked about immunosuppressive drugs and then HIV, which is a natural way of acquired immune deficiency. HIV human immunodeficiency virus, it will also genus lentivirus, it's a retrovirus if you remove it from Chapter 13. And HIV has double strands of ordinate, which they're both positive, meaning that they both act can act as an enemy. Also, they have a reverse transcriptase enzyme, which, you know, they have RNA. But reverse transcriptase will enable these viruses to make DNA from RNA. And then they also have integrase enzymes, so the function of integrase enzyme is to integrate, right. Or corporate corporate incorporate the viral DNA into the host DNA.
That's what integrase does. They have envelope, the envelope is phospholipid, they also have these spikes, these spikes for attachment spikes or glycoprotein molecule. And so this is how an HIV looks like. Double standards, standard name and the spikes and the spike is a glycoprotein which actually binds to a receptor. So here's a cell and primarily they bind healthy cell. They want help, Cecil's helper T cells are the ones that have Cedefop receptor, if you remember, we talked about that in previous chat. There are other types of cells in the body that have seed for the other ones are dendritic cells, as you mentioned here. But maybe here. Yeah, macrophages, the right cells, macrophages. So those are have said before primarily the bond helper T cells. So anyway, the what I'm trying to say is that it's not just that receptor there that they point to something else is also required there, which is not showing in this picture. But you will see it in the next one, which will be a receptor. There's also a receptor on the surface of these cells, which. They also point to not just in September, the chorus of. And not as that, because it has an envelope, the envelope kind of fuses with the cell membrane and the spikes on the envelope stays out there, the content comes in, and as soon as it's in, then the protein code is going to be dissolved. Thus on coating. Right. Like any other animal virus. And then the ordinates free the cell. These are the integrase, I believe, enzymes.
We see.
Or it might be the remedy what they with their. Well, these are the reverse transcriptase inside the integrase are enzymes that are here. So these are the and does a mother. They have all the enzymes for it. So I notice that once once they enter the cell.
Two things happen. Where is the active infection, that's where new viruses are produced and the cell is making we're talking about that hepatitis and specifically here, as you can see, new viruses are being released because this is an envelope virus is going to release us with a boy buddy. So the cell will not rupture my body. So when new viruses are being produced by a that's called active infection as opposed to later detection, latent infection is when the viral DNA has incorporated into into the host's DNA. So it exists there as a protest. Right. Remember, there's approvals now and there are no new viruses being produced. Right. All the all the genes are active except the genes that would make new viruses. Those are not active during latency. How long would latency take? About 10 years. And in in the type subtype of HIV that exists primarily in West Africa, that has a shorter it has a shorter latency latency time, latency time and also. Lower viral load and decreased mortality rate. That's type two, we have a like one that is 99 percent of most of the world has type one and there are there are more subtypes. But anyway, so during the time that process is informal for a virus, no new viruses are produced. That's called latent. This is latent. This is active. So I notice that, you know, Heggarty cells. Yes, they're the primary cells that. All affected, but also the they can't similarly bind to the city for the same receptor that also macrophages do have a drug Exocet. So like this is a macrophage. So notice that it gives a macrophages. Yes, they can make the virus in their. But also the whole virus, not as a whole. It is a symbol, but there in the vacuoles, in their. So in the Microfit, that can't happen here. So they can persist as providers or as complete lawyers in these vacuoles. And what's worse is that as long as a form of progress or even if all those in the microphages in those magill's, they're hidden from our immune system. He hidden from what immune system and.
Activated again when new viruses are being produced.
So two forms. This is showing you the viral load also
shows what is happening to our T. T cells of the person who is infected. The what the HIV infection is actually composed of three phases. And each face has different characteristics that we were talking about in the next slide, but the first phase is called asymptomatic. Or chronic lymphadenopathy, because that's what happens in phase one either. There is absolutely no symptom the person doesn't know that he or she is infected or might just have been largely ignored every once in a while. Phase two is symptomatic, and we're going to look at some of the early signs of, you know, where those early signs were HIV, the person is infected with HIV like thrush. So we're going to talk about some of those. And which is an indication of the sort of immune system breaking down our last phase is called AIDS, so clinical AIDS is the phase three before that is not called clinical AIDS. Before that is just called HIV infection. Clinical aids is when the number of TI. T cells. Drop below 200 cells per micro microliters. Normal count is 500 to 1500. When it drops below 200, that's quite critical. It's.
So, again, these are hepatitis C, therefore, is unhealthy, so sedate is on cytotoxic notice that these are healthy cells, right? So let's look at
what what else is happening here. So initially is this is three months after infection, six months after infection, ten years after infection. So notice that the helper T cells are steadily population is going down. And initial infection is that you do have the HIV population in the blood, first infected is high, but see how the HIV population in the blood is has stabilized in here and then it starts school. So meaning that meaning that during the time that the person doesn't even know if she infected the population of HIV in blood is kept stable, but then thus usually during latency. And then when it goes up, so goes go up if the person is not treated, about 100 billion new viruses are produced every day if the person is not treated.
So in about two months, notice that the HIV, the blood peak's. And then why does it drop is because of immune system that is fighting it? So this traffic.
And that is a surprise what seroconversion here is that, you see, seroconversion happens when you can they can detect the first antibodies against HIV in the blood. So before seroconversion has happened, nobody can tell if the person was infected. Because there are no detectable antibody. So how long is that like about one, two to three months? You know, when seroconversion has not happened yet. After that, then you can see the first antibodies against.
All right, so now look at this, look at the. What are some of the signs and symptoms events during each face? So remember phase one? The first one was called asymptomatic because there are no absolutely no symptoms or maybe just enlarged lymph nodes. Phase two is when helper T cells are declining steadily. And what are some of the things that the patient is experiencing? Persistent fever, persistent diarrhea. Or, look, Appalachia, which is white patches on the on the tongue. As well as THRUSH that I mentioned, thus candidate begins in fiction of the mouth. Of the Tom. That I have talked about that before, how that can be any sign of actually fiction. And also, that could involve even the throat and budget of. Shingles might show up. So if anybody has had smallpox as a child now those those viruses, the providers is activated and they will show up at shingles. And also precancerous or cancerous cervix in women. So those are some of the things that develop or are seen in patients, HIV patients who are now experiencing the second phase and the third phase, which is called clinical AIDS. That's as I mentioned again, when the third party sales number dropped below 200 per micrometer. Now, other things are happening here, but this is clinical AIDS where you have now candida infection of deeper esophagus, bronchi, you know, not the lungs are involved. Tuberculosis, cytomegalovirus, infection of the eyes, pneumocystis pneumonia, fungal infection of the lungs, the plasma cells of the brain, and Kaposi's sarcoma, which is cancer of the connective tissue. Of skin and blood that we talked about before then, usually, you know, these are these are these this is these are secondary infections are developing. They die from it. So they're not dying of HIV. They're dying of these eventually.
They also say that. No, this is not. Is not that HIV is infecting the healthy cells, but.
Inability of the body to make more. Of those T cells. To compensate for the ones that are infected, that's what actually causes the disease in it and eventually, you know. These the patient will die of this inability of the patient of the immune system to compensate for those
T cells that are infected by making more and more cannot keep up. OK, I'll let you read through this the mode of transmission and also modes of transmission and also the
prevalence of AIDS in different parts of the world. The last slide I want to talk about is this one, which is some of the new medications that are developed and what are they targeting? For HIV, so there are medications you a of these two you've you've heard of of Iraq before from Chapter 20, that's the one that prevents the fusion of HIV, a virus envelope with a cell membrane. So these two are preventing the fusion. And then if you cannot fuse, it cannot enter. Right. And then the second group of medications like of Tenofovir you've heard of before, this is the one that inactivates reverse transcriptase enzyme. So if the reverse transcriptase enzyme is not working, that means the bacteria, the virus cannot make DNA from its RNA. It only has ordinate. So those are how the weather this is what they're targeting other ones. This one is targeting integrase, enzyme integrations that would enable the viral DNA to integrate itself into the DNA of the cell host. Inactivate that so they cannot become providers. Yet we have those that inactivate the protease to break down the proteins enzyme of the virus. What this is doing is that protease will break down protein in order to use it for capsid, for example, the consumers of capsid. So it will prevent that from happening. So interfering with the maturation. And yet we still have other medications which are not mentioned here that are interfering with the process of release from the cell. So you need to memorize the name of the medications. You know, some of them you've heard in the interview and you have heard before. Same thing with second of you. You already know these are anti HIV, but you're not I'm not require you to memorize these specific names and what step they are involved with. But, you know, you need to know what targets
in this viral infection, this HIV infection, what are the targets that are used?
And what are they supposed to accomplish with these targets? That's what I want you to know. Not necessarily the name of the medications, but the name of the targets. And what are they accomplishing with those? All right. That was the last slide you guys talk to later.
Chapter 19. Hypersensitivity reactions are disorders involving the immune system, and this chapter also discusses failures of the immune system.
Immune System Failures
Infections: Occur when the immune system fails to eliminate pathogens, allowing them to proliferate.
Cancer: A breakdown in immune system function leads to cancer development due to lack of immunological surveillance (e.g., natural killer cells). Elderly individuals are more susceptible because their immune systems degrade over time, and young children may also be at risk as their immune systems are immature.
Medications: Certain drugs are prescribed to suppress the immune system, particularly for patients undergoing tissue or organ transplants or treating specific cancers.
Autoimmune Diseases
More prevalent in women, with genetic predispositions affecting susceptibility.
Autoimmune diseases happen due to a loss of self-tolerance, where the immune system cannot distinguish self from non-self molecules.
Examples:
Transplant Rejection: The immune system attacks transplanted tissues.
Blood Transfusion Reactions: Occur with incompatible blood types.
Hypersensitivity Reactions: Allergic reactions considered unwanted immune responses, where the immune reaction is exaggerated.
Allergen studies since the 1970s indicate a rise in allergies and asthma, referred to as the hygiene hypothesis, suggesting reduced exposure to microbes in urban settings contributes to this increase.
Clostridium Difficile
A harmful bacterium associated with increased antibiotic use leading to microbiota imbalances and inflammatory bowel disease.
Treatment may involve fecal transplants to restore normal microbiota.
Inflammatory Bowel Diseases
Include Ulcerative Colitis and Crohn's Disease, both characterized by chronic inflammation of the gastrointestinal tract. Treatments may involve experimental therapies like ingestion of whipworm eggs to modulate immune responses.
Hypersensitivity Reactions
Divided into four types based on mechanisms:
Type I (Anaphylactic): Quick local or systemic reactions due to IgE antibodies binding to allergens (e.g., pollen, insect venom).
Type II (Cytotoxic): Involves IgG or IgM antibodies causing cell destruction or dysfunction (e.g., blood transfusion reactions).
Type III (Immune Complex): Caused by immune complexes depositing and triggering inflammation (e.g., arthus reaction).
Type IV (Delayed-Type/Cell-Mediated): T-cell mediated responses occurring days after exposure (e.g., contact dermatitis from poison ivy).
Cancer and the Immune System
Immune system failures can lead to cancer development due to ineffective tumor cell recognition. Treatments may involve immunotherapy using monoclonal antibodies to target cancer cells directly.
Immune Deficiencies:
Congenital (Primary): Genetic immune deficiencies such as SCID.
Acquired (Secondary): Resulting from HIV/AIDS, certain cancers, or medical treatments suppressing immune function.
Transplantation
Tissue rejection due to immune response against non-self cells.
Types of Grafts: Autografts (from self), allografts (from others), and xenografts (from animals) have different rejection rates.
Immunosuppressive drugs are necessary post-transplant to prevent rejection but increase infection and cancer risks.
Disease Prevention and Medications
Preventative measures include vaccination against common cancers linked to viral infections (e.g., HPV, Hepatitis).
New treatments target HIV at various stages of its life cycle, aimed at preventing integration, replication, and release of new virions.