Secondary Immune Deficiency Pt 1 Transcript PDF

pneumoniae causes, in fact, pneumoniae. Sorry, you guys. It's not critical to this discussion, but strep pneumoniae causes pneumonia. Strep-iogenes causes strep throat. And so, there are many different serotypes of S. pneumoniae, and they all have antigenically different, so these are all the dif...

pneumoniae causes, in fact, pneumoniae. Sorry, you guys. It's not critical to this discussion, but strep pneumoniae causes pneumonia. Strep-iogenes causes strep throat. And so, there are many different serotypes of S. pneumoniae, and they all have antigenically different, so these are all the different antigens on the surface, but they're all different capsular polysaccharides on their surface here. And so, they all differ in terms of the shape. Like, yeah, these are both, you know, rectangles, but this one's orange, and this one's pale blue. These are triangles, but this one's green, and this one's like blue or purple or whatever. And so, a person can become infected with one serotype of strep pneumoniae. You know, you go through normal immune response, we make antibodies, we clear the infection, voila, antibodies bind on. However, these are, you know, antibodies are made for these yellow triangles here. So, if you get infected with a different serotype, like the blue circles here, these antibodies won't recognize this new serotype of S. pneumoniae. And so, as a consequence of it, you have to make a new immune response to it in order to clear this infection, because there are a lot of different, you know, capsular polysaccharides. You can get infected with strep pneumoniae many different times, and it's not just saying that your immune system is not, you're not immunodeficient, your immune system is not doing its job. There are just a lot of different serotypes that come are here to subvert your immune system overall. And so, again, just because you keep getting strep pneumoniae does not mean you have an autoimmune, or immunodeficiency, it does mean that, you know, strep kind of sucks. It's a very, very effective pathogen. Another example is that you have mutation or a combination allow the influenza virus to escape from immunity. So, we use that example last class too, like prior classes where, like, they can, you know, shift their different antigens on the surface, and so, like, your body doesn't recognize them overall, and they change enough that, you know, Nathan could cough on his neighbor, but still get infected with the strea, because by the time it reaches Sabrina, it's mutated enough, but it doesn't look like the virus that he's already encountered here too. So, there are two main terms we use with influenza specifically. We have something known as antigenic drift and antigenic shift. I always like to keep them straight in my head by thinking of drift as, like, a very peaceful little tiny wave, like, you know, you're, you're drifting in a wading pool, like, it's not, it's peaceful, it's slow, nothing crazy. When you think of a shift, I think of, like, an earthquake and a gigantic change in something, or, like, a shift in the tectonic plate, it's, like, a big deal. So, antigenic drift is minor small point mutations overall that just slowly and gradually cause alterations to the structure of viral surface antigens. This is what causes our year-to-year antigenic differences in strains in influenza and why we need, you know, that annual vaccine, because, again, that, you know, every single time a new person gets infected, there are those tiny point mutations, they just drift along, and they just, you know, change. So, by the time you, you know, see the same potential virus again that's just been circulating around your class, you don't have antibodies that recognize it anymore, just because, you know, again, it's drifted with each new infection, versus a shift. A shift is a major jump, and that's what we're seeing right now with H5N1, where it was jumping from cows and pigs to now humans. And what happens is this, we'll talk about this a lot more in micro, but this is specifically when influenza viruses completely reassort their segmented genomes, and this is why they're able to, like, you know, take pieces of cow influenza or sheep influenza or pig influenza or whatever and mix it together because it has segmented genomes. So, its genome is not one linear line, it's pieces of it. And so, as a consequence, if you have an animal, and it's usually like, you know, pigs, etc., get infected with both human influenza and, like, a cow or, you know, any other animal, you can have this change where those segmented genomes will swap, thus giving you radically different surface antigens than things we haven't seen before. Like, if you've never been infected with a pig influenza because we're not pigs, you're not gonna have antibodies to these new, you know, pig antigens. And so, this gives us rise to new viruses, which is caused by this antigenic shift, and they're the usual cause of our influenza pandemic. So, what we're seeing right now with H5N1 is a perfect example of an antigenic shift. Or bird fluid, I went through, or swine fluid in 2009. That was another big example of that one, too. And so, this is showing you the evolution by antigenic drift up here. And so, again, antibody will bind on to hemagglutin, a protein found with viruses here. And this will actually prevent the virus, we're gonna call it virus V, from infecting this person P here. We're gonna say Nathan. I'm just kidding. And so, antibodies de-bind on, neutralize, and prevent it from binding on here. But then, this virus goes on and infects person Q, and this virus originally mutates to give us this, you know, virus kind of a tiny point mutation here. It has this altered hemagglutin. And so, person P doesn't have antibodies that recognize this anymore. And so, when this new virus comes back and, you know, is exposed to person P, person P has no neutralizing antibodies against this new, you know, minorly changed virus V. And so, as a consequence of this, this person can now be infected because those antibodies are basically, you know, pointless at this point here. We get H, or not HIV, influenza names, like when we talk about H5N1. Those come from the terms hemagglutin and the neuraminidase, obviously. Hemagglutin is the H, neuraminidase is the N. There are a lot of different varieties. That's why we have, like, H1N2, because that's the second neuraminidase, and the first hemagglutin, or H5N1, is the fifth hemagglutin we've identified, the first neuraminidase. And so, there's being, there's various mixtures and things like that, that will create overall. But again, these are showing those tiny little point mutations that just, you know, change it just a little bit here, to the point that person P, who had antibodies against the original virus, is no longer protected just because of this tiny point mutation change. Versus when we talk about an antigenic shift. This is when, I mean, you frequently use pigs because pigs, unfortunately, are common vectors of these guys here, but they can be infected by a lot of different types of influenza. And so, this one pig cell, or one pig, became infected with both a human influenza and a bird flu. And since they have segmented genomes and pieces of it, what it's showing here is this reassorbent, where, you know, this new virus gets a recombination of a piece of an avian influenza and some human virus that creates this whole new variety of human gluten in this specific example. And no humans have antibodies to this because, again, it came from birds. We hadn't seen it before. But again, it took a just enough mutation, where it picked up some humans and some birds here, that it caused a massive shift. And so, none of us, you know, have protection against this. And so, our entire population will then become vulnerable to infection. That's why it's been so critical with HIVN1 to isolate in quarantine, especially when they found out animals have it. And we do frequent animal testing, especially if you live on a farm, to make sure there are no new viruses popping up, because then they're just, they'll just kill all the animals to kind of prevent it from spreading, because that's one of our best, you know, our best, our best defense is a good offense. So, we will do that instead. But unfortunately, we do see humans spread now with this current HIVN1, but we are still trying to keep it limited and quarantine people as soon as we find it. So, another thing we'll talk about are trypanosomes. And they are, you know, eukaryotic pathogens here, and they use gene conversions in order to change their surface antigens overall here. So, don't panic by this picture. It's just kind of showing you some genetics. Don't stress. It's showing you antigenic variation by African trypanosomes, allows them to escape from adaptive immunity overall. We'll talk about this a lot in micro, because they are pretty cool. They cause African sleeping sickness. But they have many inactive genes. So, say this is a variable surface gene on the surface. And so, you know, genes for their various surface antigen here. But they only have one site for expression. And so, they only have one variable surface antigen presented on their surfaces at a time. And so, once you have antibodies made to that specific antigen, it can actually go through and alter which gene is expressed, which would then give you a new surface antigen expressed on the surface here. And this one's showing you this, you know, B. This started out as A. And so, you know, we get infected. The body makes antibodies to A, starts controlling the infection. The parasite realizes that, moves on, expresses this second B on the surface here, which is different from the first. Our body has no antibodies to it. So, we have a flare of an infection. It activates the immune response. The body starts making antibodies to it. And then, I lost my mouse. But we would move on. And same thing. The parasite would start expressing C, because again, it's trying to subvert our immune system and expresses a new surface antigen. So, look, there's over a thousand different ones that it could use overall. And so, with patients who have this infection, we're going to see peaks of disease, because we're showing here, we're showing here that these are the disease that were being presented here in the red. So, that's the red box here. But then, notice this dashed line is showing antibodies that we created for it. And so, again, we see trypanism infection decrease, because again, we have antibodies that are controlling it. However, during this process, it realizes, you know, the body is making antibodies to it. It goes through and changes that variable surface antigen. And so, again, we have no antibodies to this. And so, we get a brief peak in infection again. If your body makes antibodies to this new variable surface antigen, controlling it. And then, it'll do the same thing again. It swaps it and makes the blue one. And so, again, you have a brief period of disease before the body catches up and makes antibodies to that one. And it'll just continue on and on and on and on and on. So, we frequently see recurrent infections with the same parasite in African trypanosomiasis, just because of this variable surface antigen that it has. It doesn't mean that a patient is immunodeficient. It just means these parasites are very, very good. Another example to talk about is herpes virus. Herpes viruses persist and we have chronic infections to it, not due to immunodeficiency, but because these viruses go latent and hide from the immune response. And so, one example here is that with an initial herpes infection, you do have, you know, the breakout along the mouth, but you will have clearance by an immune response. And so, that causes the virus to travel up the trigeminal ganglia and hide out, actually, in the brain here. And again, you have immune control of it. However, in times of stress, in times of stress, so even menstruation, sunlight, exams, things like that can trigger, you know, it suppresses the immune system a little bit and trigger reactivation of the virus, where the virus travels back down to it and starts infection all over again because it travels back down the trigeminal ganglia and causes infection on the surface. Your body amounts a successful immune response, clears the cold source. Again, the virus travels back up and remains latent. And so, it's just back and forth and back and forth and back and forth. Doesn't mean you are immunocompromised. It just means the virus is really good at hiding and subverting your immune response. There's other things that they can do, like they can directly attack our immune system, too. Like we can subvert immunoglobulin A by bacterial immunoglobulin A binding proteins. So, they can actually, you know, attack IgA and mucosal membranes. That makes you very, very good at causing infection, like your sinuses and things like that. And so, as you guys kind of remember from the last module, you know, IgA can recognize bacteria. In this case, it binds on and you have those FC receptors. And again, look, it's alpha for the IgA. Binds on recognizes that FC region tail, you know, pulls it in and, you know, phagocytizes it, destroys it, host wins. Bravo, great job here. But we have certain proteins, like SLLP7 is one example here, that will actually bind on to complement C5 and that FC region of an antibody. And if you see it here, it's blocking that tail. Because the tail is here, that FC alpha receptor does not, you know, see it. It's been blocked. And also, too, it's presenting a C5 on a surface. So, it looks like it's hiding out in between. It looks like host. The body won't recognize it. And this is able to subvert the immune system and kind of, you know, beat your immune system overall. And so, in this case, the pathogen would win because it's kind of, you know, hiding out and protecting your body and subverting its normal immune response here. This is what's known as a superantigen, though, SLLP7 specifically. And so, it is an example of a superantigen. It's not elaborated in this picture here. But just by definition, I want you guys to know this just because we will talk about this a little bit more with microbiology. But a superantigen is a molecule that, by binding non-specifically to MAC class II molecules and T cell receptors, will actually stimulate polyclonal activity of T cells. So, we just showed one example with SLLP7. But something else that it can do, too, is it can actually trigger T cells to divide and activate them without them, thus kind of leading to, like, autoimmune disorders because the body is so, like, it's activated. There's lots of division. It's trying to fight something. It doesn't know what's going on. So, it's basically like a distraction. It's telling the body to attack itself and look at the other things. Meanwhile, the bacteria subverts and survives. So, there's a lot of, you know, nifty ways that bacteria are constantly trying to fight back and not keep us safe overall. And so, obviously, if we have a failure of the immune system, we have a reduced ability to resist infection. And so, you know, that's why you can see these diseases here. It doesn't always mean it's an immunodeficiency disorder, but immunodeficiency disorders are specifically where we've taken out an aspect of the immune system, usually genetically, especially when we talk about primary immunodeficiency disorders. But we will talk about secondary today because these are caused by the environment, or we've damaged the immune system later. And some of them are viral, so certain infections can lead to immunodeficiency. We'll talk about HIV a lot today because HIV is one of those few examples, because it really actually destroys the immune system. It depletes your CD4 T cell count. And obviously, if you take out T cells, you can't mount successful adaptive immune responses overall. You've taken out the general of the army. Other therapeutic treatments, like certain drugs, even cancer and chemotherapy, can deplete the immune system too, because like radiation can destroy immune cells, you can damage the bone marrow, stuff like that. And malnutrition, if you don't have the proper nutrients, can lead to the development of immunodeficiencies, because again, you don't have the nutrients needed for the cells to function basically in the normal. With these guys, they occur at any time in life, depending on when the exposure of the causative factor occurs. But it is important to remember both primary and secondary are characterized by our current or chronic infections, obviously excluding herpes and stuff like that. Some can make you more susceptible, but again, herpes is just nasty on its own. The variable surface antigens of trypanosomiasis, it doesn't mean you have an immunodeficiency. It's just those are very good parasites and pathogens overall. But you will have also an inability to clear infectious agents after standard antibiotic therapy too, which is important because again, antibiotics should help kill off bacteria. And if you're still with a antibiotic bacteria susceptible to and your immune system, you should be able to clear it. And if you don't, something's wrong. Or if you get infected by really weird pathogens that are usually not seen in humans, something else is probably up. This is just a really pretty picture overall. I actually forgot what this picture was. Oh, it's HIV virus. It's blue, the blue dots being shed from an infected T cell. Because again, HIV is an example of a secondary immunodeficiency disorder because it takes out and destroys your T cells, uses them to make new baby viruses and viral factories. Unfortunately, thus spreading the virus and when you take out the CE4 T cell in general, you have immunodeficiencies overall. So it does arise from environmental exposures that may occur at any time in life, depending on when an exposure occurs. So when we talk about secondary immune deficiency, HIV is one of them. Environmental factors, like we mentioned before, could be physiological sequelae, like malnutrition. If you don't have the nutrients you need, therapeutic treatment like chemotherapy can affect, or certain drugs can affect your immune system here. Obviously having cancer, if you have malignant lymphocytes or monocytes like lymphomas and leukemias, it can crowd out normal hematopoietic cells like we talked about, kind of like you have a limited amount of volume. And if it's taken out by a million different lymphocytes that the cancers are not really functioning well, you could lose your monocytes and therefore have decreases in macrophages too, or lower levels of neutrophils, things like that. Or infection, which is HIV here. The status from 2019, they really haven't updated too much of it then, but even back then there were over 38 million people living with HIV. The number is definitely for sure gone up. Newly infected, we had roughly 1.7 million new people infected, and with death we had roughly 700,000 deaths overall. I don't know why it says million there, because it's not million. But it does increase and there's breakdown of children, men, women, and adults overall. Now we look at HIV virus. We'll learn a lot of these guys more so next semester here, but this is what it looks like when they're getting electromicrograph that's been colored. You have spike proteins on the surface, so not just COVID. Lots of viruses have spike proteins on the surface here, but it is a retrovirus, which is really cool because it is an RNA virus. And as you guys know, central dogma of molecular biology is DNA to RNA to protein. We call it retro because it's going backwards. Again, if you're showing close from the 80s, it's retro now apparently. But it's backwards because it does go against that central dogma of molecular biology because it uses reverse transcriptase to actually take its RNA virus, convert it into DNA, and actually insert itself into your genome so you have it for the rest of your life. And so it breaks that central dogma of molecular biology, which is why we call it a retrovirus here. HIV can infect CD4 T cells, monocytes or macrophages, and even dendritic cells. So it can affect a lot of different aspects of the immune system, both the innate and adaptive overall. And we will stop here just because I think I'm over time on the recording here. Obviously there are a lot of different proteins involved before you guys panic. I would know just these these three that I bolded here and then these two here because they're actually different subtypes of the virus, mainly HIV1 and we differentiate them by the presentation of VPU and VPX. So I would know because it's bolded, VPU, VPX, gag, pull, and envelope. VPU, VPX, gag, pull, and envelope. And so they are described here. There's a lot more than just that, but I would know those for sure. And we will stop there for today.