Transcript for:
Disorders of the Immune Response

okay so in chapter 16 we're going to look at disorders of the immune response so the first kind of class of disorders we're talking about are the hypersensitivity and what we're saying here is that we have an excessive or inappropriate activation of the immune response where basically it's going to be much stronger than normal or inappropriate where you can start attacking your own body's tissues now we find that is that we technically have a hypersensitivity interest if your body tissues are damaged by the immune response rather than by the antigen or you know sort of the pathogen it might be trying to fight off and so you know the questions we have here are things like you know what allergies are you afflicted by and orders from the common time symptoms of those allergies and how does this relate to inflammation well remember we talked about with inflammation there's a five cardinal signs we talked about how there is redness heat pain swelling and the fifth is a loss of function so what we're really going to focus on then with the hypersensitivities is how do we get lots of function then if it's all about inflammation here because that's going to lead a tissue damage that's associated with the hypersensitivities and which makes them dangerous and therefore pathogenic and that's why we talk about it here in pathophysiology so the first type of hypersensitivity we'll talk about is type 1 type 1 is commonly associated with allergies so this is like allergic reactions and these can either be systemic or in a phylactery as well with local hypersensitivities you're talking about seeing things like your to carry out or hive you know rhinitis which is you know hay fever just runny of those atopic dermatitis so essentially just you know itching the skin in a local area and then you know bronchial asthma where we see some kind of constriction of the Airways type 1 hypersensitivity are also associated with food allergies so in terms of the mechanism of how these occur what happens is we actually have these T helper cells which are kind of already primed against the particular antigen so you'd find then that you know if these T helper cells were already kind of hypersensitive to an antigen and this antigen could be foreign you know like let's say like an oil of like a tree nuts and that's why that's why you're looking to tree nuts or it could be you know latex given a latex allergy now essentially what happens here is that once the T helper cells are activated they can release inflammatory cytokines and these specific ones we have are the interleukins to have interleukin 4 3 & 5 here and these interleukins go on in the excite other leukocytes it's what they call interleukins between leukocytes so the in looking for here that excites B cells and these B cell starts to turn into plasma cells and they turn into I GE secreting antibody factories right remember we have said that the IgE antibodies are the ones that were more commonly associated with allergy and these other n illusions here can activate nearby eosinophils which are going to lead to more long term later responses but let's come back to up here with the IgE secreting plasma cells now happens is that these iges are basically picked up by mast cells and these mast cells in response to the IgE s become hyper synthesized and so what happens then is that these mast cells then that are hypersensitive by the IgE can then also respond to the same antigen that these T helper cells were sensitive to earlier and so what happens in is that these mast cells quickly D granulate and we talked about how the granulation of mast cells was the rapid release of histamine and other inflammatory mediators so some of the early response would be do the histamine so we see vasodilation a little bit of increase in vascular permeability and maybe some damage from that as well as smooth muscle spasm and this is consistent with the early phases of the inflammatory response nowadays the dilation here is what's going to increase blood flow and bring in the the redness and the heat to a local area and then remember when vascular like blood vessels become more leaky this is what's going to lead to the swelling and the smooth muscle spasms can leave the blood clot now we also get the release of cytokines which can activate other inflammatory cells and these mast cells can release prostaglandins and leukotrienes which can also contribute to more of these late response so later on in the type of hypersensitivity he remembers an allergy we can see things like mucosal edema retro sort of swelling of the mucous membrane wherever that might be just the nasal cavity you get rhinitis could be the gastrointestinal tract wherever those in you cook mucosal membrane we get an increase in mucus secretion which can plug Airways it can be uncomfortable and we can also get things like epithelial damage which comes from that loss of function right excessive inflammation and then the infiltration of leukocytes and possibly even bronchospasms where individuals Airways start to you know become more narrow that increases resistance which decreases flow so that individuals can have difficulty breathing in here and so we find that is that the cellular mechanisms of the type or sensitivity lead to the some of the more common symptoms and signs of what we think about in terms of allergy so type 1 allergies are mediated by number IgE and IgE antibodies were the ones that are associated with allergies now they're secreted by b-cells right that plasma cells rather and but then what happens is that it's the mast cells that interact with these IgE antibodies and this makes individuals even more sensitive to that antigen and so on the first exposure to an allergen what happens is you're going to have the sensitized T helper cells that then release cytokines that can activate b-cells that even release IgE and then upon repeated exposure what happens here is that individuals who've already been exposed to the allergen in the past have our mast cells with our I GE antibodies already on them they're hyper sensitized to that allergen and they're going to get a really rapid response because a hypersensitivity there and when the allergen binds the IgE then the mast cells are going to quickly be granulate and that's going to lead to a pretty rapid inflammatory response so early on the inflammatory mediators that are involved would include things like histamine we get other cytokines and release as well as prostaglandins and leukotrienes that can lead to some of the secondary responses you know like the the costal edema you know mucus production that kind of stuff now the question here it says true or false when mast cell degranulation histamine is released and we just talked about how that's true right histamine is one of the first chemical mediators released during the inflammatory response and mast cell mast cell stabilizers things that are used to treat asthma basically are anti histamine right they prevent histamine from being released and we can use anti stemming to treat allergies not cure them but treat them because this is going to help to diminish the signs and symptoms of the allergic reaction and the way these work is they compete with histamine for different receptor sites which come dampens down the inflammatory response so an example here is an AFOL axis right so anaphylaxis would be more like the systemic response to an allergen and this is where we have so many inflammatory mediators that are released as a consequence of a type 1 hypersensitivity that it can lead to massive vasodilation right we're talking about not in a local area but histamine acetylcholine Kainan leukotrienes and prostaglandins they all cause vasodilation but what these inflammatory mediators go systemic well stand up in your bloodstream and to get vasodilation all over then what that's going to do is it's going to limit blood flow you're going to decrease resistance and it's also going to decrease your blood pressure and so we're talking about how individuals can begin to go into shock from anaphylaxis because their blood pressure could be so low that blood stops flowing and they can't supply nutrients to their body's tissues now many of these also cause bronchoconstriction by acting on the smooth muscle of your Airways so if your Airways constrict we're going to see even as a limited airflow as well because of that increase in resistance you're going to decrease flow and then people are going to have sort of respiratory symptoms of this as well so the anaphylaxis is an interesting combination of people who have extremely low blood pressure and difficulty breathing and together it could be life-threatening now we have a scenario here says the woman had anaphylactic reaction and you're trying to explain the mechanism to her husband he says he can't see what you mean I'm sorry you can't see we mean but it does not make sense because this life experience was different her heart was pounding she was terrified and her eyes were dilated pupils are dilated and she was shaking so the question here is how could anaphylaxis cause these signs and symptoms well it's not the anaphylaxis itself that's causing these particular signs symptoms but rather if someone's self monitoring their own internal body states like anaphylaxis can be pretty terrifying you know they with that decrease in blood pressure they can become dizzy disoriented and when they when their airway start to constrict through bronchoconstriction they have difficulty breathing and that in itself is terrifying right like it brings terror and that's going to be a sympathetic response we know the sympathetic nervous system acts to increase heart rate causes pupillary dilation and the shaking can just be from excessive you know muscle muscle activity so we find that is that you know anaphylaxis isn't causing it directly but rather leading to a psychological phenomenon where the individual gets scared and you know it has they have these kind of these kind of signs and symptoms now with a type 2 hypersensitivity similar to type 1 hypersensitivity in the sense that antibody mediated but what's happening here is that it's not an involvement of IgE rather some involvement with the IgG and IgM antibodies remember IgM is the large one it's made of five different antibodies they're all strung together into a kind of circular chain but IG G can be cut from IgM so they're similar in that regard now what happens here in this particular type of hypersensitivity is we have Auto antibodies so these antibodies here can bind the antigens on cell surfaces right we're saying that these antibodies can bind at red blood cells white blood cells and this can be associated with transfusion reactions or different drug reactions now when these antibodies bind to your own body tissues it can cause a variety of diseases like there's certain types of epilepsy that are caused by type 2 hypersensitivity where you know your own antibodies can start to excite neurons in your brain that leads to firestorms of electrical activity now these antibodies can also bind to things like TSH receptors in your IRA which can lead to excessive you know thyroid hormone or in Mycenae gravis you know these antibodies can find from the Katyn ik receptors that skeletal muscle and they can block those receptors which then actually lead some muscular weakness now in terms of the mechanism of type q hypersensitivities what's going on here remember it's antibody mediated and we're come on IgG and IgM s now this can come about if essentially you know we have Fager sites that might recognize a particular antigen and they say grosseto spent and antigen-antibody complex remember it's Auto antibody it can also occur like antibodies them you know can recognize antigens on the cell surface here and that can lead to activation of complement which can lead to inflammation in damage to these cells can also occur where free antibodies actually interact with different receptors so with see here this is an interesting phenomenon where Auto antibodies here their IDs that bind to TSH receptors but instead of blocking them they activate them because this antibody acts like thyroid stimulating hormone so when the antibody binds the receptor it actually leads to a stimulation of these thyroid cells the follicular cells in thyroid which leads to an increase in thyroid hormone production so this is actually a type of hyperthyroidism that's caused by a type 2 hypersensitivity it's also possible to for these antibodies to bind and block receptors so in the case of myasthenia gravis what happens here is these antibodies bind to the nicotinic receptors on skeletal muscle and they block the binding site for acetylcholine so the skeletal muscle ends up getting paralyzed as a result so don't activate the receptors actually blocking it now with the scenario here we says we say that a woman is Rh negative and her husband is Rh positive number RH factors reaches factor that's going to give you the negative or positive sign your blood type and she's pregnant with their first child the doctor prescribed rhogam but the woman's confused she says that she doesn't want to take any drugs while she's pregnant the doctor told her that her first child was not as much of a risk for for RH disease so RH disease would be a referral so sweet Alice and it's a condition where you can have an Rh positive fetus within an Rh negative mother so what happens here that if the mothers immune system recognizes Rh factor on fetal blood cells she can begin to produce antibodies against orange just to make anti RH antibodies and those antibodies can cross the placenta and start to attack basically the fetuses blood cells and so this can become a problem that can be life-threatening for the fetus so what happens then is with there's a drug called rhogam and it's an antibody against anti RH antibodies so as you can block antibodies from being able to cross the placenta by using this drug now it's not a drug in the traditional sense it's actually antibodies that are made in a lab but this is useful to take if you're thinking about you know an individual who might be at risk of producing antibodies against their fetuses antigens now the question here says why cannot she wait to take Road game if she gets pregnant again and really needs it well the issue here then is you know upon subsequent pregnancies she's more more likely to produce anti RH antibodies if she keeps having like Rh positive fetuses and so what's going to happen then is she's more and more likely to produce that those antibodies in which is compras the placenta and basically you know attack the fetus is red blood cells now the problem though is that rhogam is an antibody now if you take this too much you can start to make antibodies against rhogam because that's a foreign antibody and so you know if you take too much of this can actually lead to you know basically a immunity against the drug which is kind of interesting now this question here says you know why is the why is the blood considered a universal donor why is Oh blood considered universal donor now the reason being is okay well we have different questions here so it says it has both a and B engine rev level has neither a or B or revolution has no antibody in the plasma or has a or b and a body's in plasma so the answer here is the fact that it is does not have a or b antigens on a red blood cell remember Type O isn't an antigen in the sense that it can like stimulate immune response o refers to the lack of a or B right so if your type of blood then you don't have a or b antigens on the red blood cell surface which is why they're considered a universal donor in that sense because there's not any antigens or a or b antigens for the recipient immune system to respond to so you know remember antigens are components that elicit an immune response like a type 2 hypersensitivity reaction so individuals who might be exposed to a foreign antigen can begin to produce antibodies to get that antigen now because type O blood doesn't have a or b engines anyone can receive it because there's nothing to stimulate the production of antibodies that attack that blood right so the fact that type O blood has both a and B antibodies doesn't really generate an antigen antibody response you know you might get type O blood an individual might actually I already have like preformed anti a or anti-b antibodies but there's not enough of those to cause a problem in the recipients body so with a type 3 hypersensitivity with interesting here that it's also similar type 1 and 2 because antibody mediated but this is a delayed hypersensitivity because it's where antibodies bind the antigens but they're inefficiently removed from the body so you get these circulating immune complexes that can deposit on the walls of your blood vessels and they can lead to damage of blood vessels and systemically this can lead to things like autoimmune vasculitis glomerular nephritis serum sickness in serum sickness is associated with things like antibiotics certain foods and Venom's but it's a delayed hypersensitivity and if it's local we call Arthus reaction so what we see here then is we have antibodies that can actually bind with antigens and these antigens are you know they can essentially be just a you know a foreign antigen and when they'd handle body bind they can precede the immune complexes that if they're not remove they can actually deposit and block blood vessel walls which can unfortunately leave the activation of complement we talked about how complement can attract inflammatory cells which can lead to excessive inflammation and with a loss of function you can guess you get damage to the nearby cellular structure and so you know we're seeing that a type 3 hypersensitivity is going to lead to more like a vascular type of disruption here because of these antibody antigen complexes build up on the blood vessels and they're particularly going to affect very vascularized tissues you know like your kidneys because your kidneys receive a tremendous amount of blood flow this is why it's going to be associated with like the glomerular nephritis ease or glomerulonephritis because this is going to damage like the capillaries of your kidney glomeruli which can lead to renal failure so the key here then is actually helping to effectively remove these antigen antibody complexes or just not being exposed to the antigens to begin with so the question here is true or false administration of certain antibiotics can result in a type 3 hypersensitivity reaction and the answer is true in fact we just saw in the last line how the antigen could be that the you know at the stimulating factor for an antibody to find and I could leave the hype texting hypersensitivity now this is actually a side effect associated with antibiotics administration like penicillin penicillin is an antigen right I mean it's a molecule that's produced by a fungus right Penicillium and this fungus is producing this as an antibiotic right well we can use this fungus molecule to fight microbes in our own bodies but it's still a foreign molecule and so what can happen is we can begin to generate antibodies against this foreign molecule and that can leave it what we call serum sickness which is a type 3 hypersensitivity reaction where people are you know they say it allergic to penicillin what they mean is that antibody antigen complexes can build up where penicillin and your own antibodies can bind they can actually deposit in blood vessels and that can lead to damage to a lot of different tissues so a type 4 hypersensitivity is different than the first three this one does not have anything to do with with antibodies rather this is cell mediated this is where t-cells are hypersensitive and what can happen here then is cytotoxic t-cells can actually be damaged as and this is also associated with certain viral reactions nobody can so there's also a delayed hypersensitivity and it can be associated with things like macrophages and T helper cells and it might be precipitated by things like the tuberculin test where they're looking for tuberculosis can also be associated with contact dermatitis and hypersensitivity pneumonitis now in terms of this mechanism what's going on here is that you know we have antigen presenting cells like macrophages that can engulf a foreign antigen right now once they present this antigen to the cd4 cells the T helper cells you know they can essentially cause excitation of cytotoxic T cells which can you know damage nearby tissues now the problem here then is that you get both direct cell toxicity like these could be antigens of your own body by the way so this could be like a form of autoimmunity but can also lead to delayed reactions to where you know these prime cd4 cells the T helper cells could later on release cytokines that lead to inflammation and you know a loss of function as a result and that could be delayed so remember type 4 hypersensitivity just think about how the macrophages are presenting antigen to like hypersensitive T helper cells and that's leaving leading to an excessive kind of t-cell mediated response here with the type 4 hypersensitivity now like with organ graft rejection these are also hypersensitivities and they could be hyper acute acute or chronic you know put the hyper acute sensitivity what we're saying that is that circulating antibodies just immediately react with the graft you know you might get a graph of a solid organ if there's already antibodies that can attach to those antigens of the graft it's hyper acute because it's going to occur immediately because they're already preformed antibodies acute could be sort of a several-day delay or weak delay we're eventually get the generation of t-cells that can that can activate B cells which can produce antibodies against the graft but you know it's going to take a little much longer than hyperacute and then when this chronic type of hypersensitivity for graft rejection we say that over time blood vessels in the grafts are gradually damaged this could result from like a type 3 hypersensitivity where you know antigens that are associated with the new organ to bind with antibodies in the host and those can deposit within blood vessels leading to damage the vasculature and kind of slow decline of the organ over time now with somatic we'd Excel rejection we're talking about bone marrow transplants right so what happens here is that the T cells that come from the bone marrow can react from with a transplant and this can lead what we call graft-versus-host disease and this occurs in individuals who might need to have a bone marrow transplant where if they had like leukemia or lymphoma and their bone marrow was wiped out through you know radiation treatments if they get a you know basically a bone marrow transplant they're receiving an entire new stem cell set from potentially someone else now the problem here that is that the transplant needs a functional immune component right so it could get this from somebody else what the host tissues can have antigens that are foreign to the donor tissue right so the host immunity can be compromised as a result in essentially what's happening here is that individuals can begin to produce new immune cells that actually are foreign not of their own body and they can start to attack the host cells and vice versa you know like your own immune cells that maybe are still existent there can begin to attack the new bone marrow that was transplanted so that's called craft versus host disease now they can difficult check for this right you're looking for MHC compatibility like if someone is very similar MHC to you you're less likely to get this graft-versus-host disease because you're going to say that that won't grow immune cells can seem to recognize you know yourselves as potentially cells if the MHC is antenna orly similar right now they can test for MHC compatibility through genetics right and but also is you can just test for this interest lab lab simulated settings where you just mix cells and see if they react now with graft-versus-host as you there's some interesting phenomenon here and we see that men who get bone marrow for women are more prone to graft-versus-host disease than men who get bone marrow from other men and so it's also suggest about children that I'm sorry that women who have more children are more likely to have grass versus host disease as well and so the question here is why might this be the case well it seems to be that they're probably the genetic component right and that can relate to gender or sex and we're saying here then is that if men get bone marrow from women then they're more likely to have different MHC so they're more likely to have graft-versus-host disease then if men get bone marrow from other men and the the component here work a woman had lot had lot lots of children right i got high parity she's a high risk for graft-versus-host disease well the child that she so the children that she's Harbor in the past or would have four antigens and so we're saying here that is that it's possible that her key cells are already sort of hypersensitive from previous pregnancies and if she gets a bone marrow transplant they're going to be even more hypersensitive into the foreign MHC and other foreign antigens and that's more likely to cause graft-versus-host disease because you'd have prior exposure to foreign tissues and that's going to put particular greater risk for responding to foreign tissues so autoimmune diseases can include but aren't limited to you know hypersensitivities so what we're saying is that autoimmune disease is that there's a destruction of the self tolerance we talked about earlier how b-cells and t-cells on when they're maturing either checked for self tolerance and essentially we want to make sure that our own immune cells don't respond to your own body antigens now if the self tolerance breaks down then the immune system can attack self antigen and therefore destroy body tissues and you think about well how many of Mada autoimmune diseases are there well I mean it's virtually the same number of ants as you can antigen in your body I mean like really any tissue your body could be subject to autoimmunity so the question here is true or false patients who suffer from autoimmune diseases have hypoactive immune systems answer is false right we're saying that autoimmune disease is a consequence of hyperactive immune systems right so we're saying that I mean immune system is too active it's overly active it starts attacking self antigen and destroys its own body tissues and what's fascinating here is that if we can look at autoimmunity as the hyperactivity of your immune system then we can actually treat autoimmunity by kind of making sure that our immune system isn't under active right if you can ensure that your immune system is like fighting off different microbes and it has less time to attack your own body tissues that can decrease the signs and symptoms of autoimmune disease in fact you see this with a with a condition called helminthic therapy right so helminth is a worm right and so how Mr P is where is the idea that you can actually give someone a parasitic worm if they have autoimmune disease because then their immune system is going to actually kind of target that parasitic worm rather than fighting off your own body's tissues and so being infected with a parasite actually can diminish the signs and symptoms of autoimmune disease and there's research labs that are working on this right now to isolate antigens that can potentially simulate what it's like to be infected with the parasite that way can treat autoimmunity in that way so immunodeficiency is the opposite of what we talked about right so it's not hypersensitivity it's not autoimmunity we're saying that immunodeficiencies could come about from an underactive immune system and this could be associated with B cells T cells it could be a combination of both like with the severe combined immunodeficiency is your s di D so an example of where this occurs was the bubble-boy right if you remember that that case and s di D are severe combined immunodeficiency is where you actually have inefficient or sort of under production of both B cells and T cells and so that they don't have an adaptive immune response there rely on on their innate immune response which really isn't good enough to fight off just the whole gambit of infection and so these individuals that are severely immunocompromised an example of like a t-cell deficiency could be with thymic hypoplasia where individuals can actually just not develop a thymus very well so they don't actually develop t-cells and so that can lead to deficiencies later in life and they have Wizkid wiskott-aldrich syndrome as well which is actually a as a heritable condition and it's excellent processes where individuals essentially inherit a defective immune system like there they don't make leukocytes that function properly and it can also be acquired too there's acquired immunodeficiency which can come from malnutrition like you need certain nutrients to support your immune system there are immunosuppressant drugs radiation can lead to immunodeficiency and even certain viruses you know we talked about like HIV that can lead to AIDS which is a form of acquired immunodeficiency so with human immunodeficiency virus or HIV it can be transmitted through a variety of ways it really is got to come from like direct contact whether that sexual contact breast milk or blood the blood contact otherwise you know it's not airborne it's not really transmitted through saliva and it wouldn't be transmitted through skin contact either unless you both had open wounds so that would be more of a blood to blood contact and so where might encounter blood the blood contact would be things like using contaminated needles having transfusions where there might be HIV in the transfused blood and possibly even during pregnancy or first where HIV can be transmitted across B placenta or to be transmitted during labor just because of you know like ruptured tissues that kind of stuff so HIV infects cd4 positive cells right and so you might wonder well what type of cells have cd4 receptors well we already talked about the T helper cells right so your T helper cells or cd4 positive which means that HIV will specifically infect T helper cells that's not good because those are the ones that are going to excite other immune cells by releasing cytokines dendritic cells are also cd4 positive that's also not good because those are the ones that crawl around in your epithelial tissues and that would be the first cell that's going to be infected by HIV because if you have a wound or something an HIV encounter is one of those dendritic cells well I can infect that dendritic cell but then drit excels are mobile they can remove her underbody they can move from skin to lymph nodes and that kind of stuff and so they can bring the HIV virus like deeper in the body work and then get closer to like T helper cells and the other type of cd4 positive cells your body are neurons right nervous cells rc4 positives so one of the interesting phenomena that happens with HIV infection is that in people can get aids dementia where over time they actually get cognitive decline that's caused by HIV infection now what's fascinating to that HIV is an RNA virus right so it's in the virion it uses RNA as its genome but if packages its own what we called reverse transcriptase and what reverse transcriptase does is it converts HIV RNA genome into a DNA strand and that can be inserted into the host cell's genome using an enzyme called integrase now it's done randomly like there's not like a specific point that the HIV genome is inserted into the host cell and that's a problem because that can actually lead to you know proto-oncogene formation so you actually convert proto-oncogenes and oncogenes if they're inserted in the wrong place so if we look at the structure of an HIV theory on here this is one infectious particle and so we see that it's actually an envelope virus so it's got a lipid bilayer this lipid bilayer has lots of glycoprotein spikes like gp120 and gp41 these are both pharmacological targets because we can actually kind of binding inhibitors where you can block gp120 and gp41 using different drugs and if you can block these glycoprotein spikes and HIV can't bind with a host cell so we actually have fusion inhibitors now HIV is a nucleo capsid as well and within this you're going to find your in a genome and it's encased in this nice little protein sheet but what's fascinating about HIV it actually packages some of its own enzymes like it packages an enzyme called reverse transcriptase it packages an enzyme called integrase and another one called protease November reverse transcriptase is the one that converts RNA in the DNA integrase is what actually helps to insert the DNA HIV genome copy into the host cell genome and then protease is are involved with basically cutting up a viral polyprotein into lots of individual polypeptides which are the viral particles or you know the viral proteins like other enzymes so if we look at the viral life cycle here we see that it first starts with fusion of HIV very on to the host cell membrane now remember it actually binds with the cd4 receptor that's how only infect cd4 positive cells is it uses that receptor to grab on to host cells and then get in now when a bind diffuses and enters the cells and diffusion and at that point what happens is the nucleo capsid enters it breaks down and you end up with HIV RNA genome with reverse transcriptase integrase and Proteus they're all there at that point now reverse transcriptase converts the RNA genome into DNA these DNA strands can actually be inserted into the host cell genome through integrase and at that point then we're saying is that the HIV genes will now be read and expressed as if they're the host cell genes and so the host cell then just starts making viral polypeptides as a result like this would be a viral mRNA this mRNA is going to be is going to carry information about how to make HIV proteins it's going to go to you know ribosomes which make viral polyprotein and then protease which is what one of the enzymes that HIV packages can cut up this poly protein into individual you know basically viral proteins that can get packaged in a new virion and those can bud out of the host cell now the reason we want to understand the lifecycle of HIV is that all of these steps our potential pharmacological targets right like we have drugs that can block gp120 and gp41 that way you can block the binding of HIV we actually have reverse transcriptase transcriptase inhibitors we have integrase inhibitors we have protease inhibitors and the cocktail of drugs that an individual with taken in would actually target all of these aspects of the viral life cycle the problem is that we don't a cure for HIV because for one it hides out in host cell DNA and you can't find it there right unless it's actually actively shedding the virus into HIV is an RNA virus it has a high mutation rate so mutates pretty quickly infected and mutate within a host body so the clinical course of HIV would be things like you know so the so the primary phase here is that we have signs this systemic infection you're going to get sort of the fever and sweating that kind of stuff and there's when we talk about seroconversion we're saying that if we can measure HIV RNA and so on bloodstream one to six months later right and so they say it to be safe to say about forever you know at four months you know you might have pure converted but it takes time to be able to measure it so you couldn't have like an exposure event and then get tested the next day and they can't tell you for sure for certain if you actually have HIV at that point it takes a while for you know the part of the viral particles to replicate to the point where we actually measure them in a blood stream now at this point the immune system can attack HIV very ons you know it's still a foreign antigen and these things can be attacked by your immune system and it's suppressed enough the virus can go into latency and latency could be you know decades and latency can occur where the virus is replicating but you know not strongly so the viral count can be very very low but the T helper cell count can gradually fall over time as a consequence of just damage to t helper cells now you know decades later this can actually lead to AIDS which is acquired immunodeficiency syndrome and this is a clinical definition where we say that individuals have less than 200 T helper cells per milliliter at that point the mutate of the dates and this is the defining illness sort of that clinical feature there now what this is going to occur with it is a lot of signs and symptoms that would correlate with a lack of T helper cells and so some of the AIDS associated illnesses would be things like opportunistic infections they're going to get a lot of really odd infections that you wouldn't find in a normal healthy individual you know odd respiratory infections especially fungi and bacteria that typically don't affect normal people are healthy people rather gastrointestinal infections that are opportunistic you know you might get a lot of things like C dis which is part of your normal flora but it's usually kept down in smaller quantities spider immune system you can get nervous system infections too like meningitis and encephalitis that are you know associated with AIDS now what's also kind of fascinating too is that AIDS is associated with different malignancies and the reason for this is that HIV when it integrates into the host cell genome it does it randomly like there's not like a place that it inserts itself into this occurs randomly sometimes this kills the host cell sometimes it does nothing to the host cell all the times you can cause mutations and those mutations can lead to malignancies and so there's different types of leukemias that are actually caused by HIV we also get different malignancies - like Kaposi's sarcoma which is actually a skin type of malignancy and they get these kind of large blueish areas in the skin it can lead to wasting where individuals just you know sort of have wasting of their body from just chronic stress as well as some metabolic disorders now in the gastrointestinal system I should also mention - is that people are at a higher risk for candidiasis so they're more likely to get Candida infections or basically yeast infections of like the oral mucosa that kind of stuff now scenario here says a man as HIV positive and he says this is nonsense because the test doesn't measure very sick or not and in fact it means that the immune system is working if you right right well if we say that the test tells them is hiv-positive what they're measuring for are not anti HIV in advice you can find that all that's going to tell you is if you have ever been exposed to HIV the more definitive tests are actually you're going to be PCR where you're looking for HIV viral transcripts and what PCR does is essentially amplify DNA you just using a primer usually gets a sample of someone's blood you can kind of search to see if they have HIV essentially genetic code there and if it's present and that suggests then that they have an infection now it's not true that that if your test positive for HIV even that means your immune system is working because they're measuring for essentially the viral genetic information not an abiding itself so that wouldn't be a correct statement so the other question here says you know one age drug is a protease inhibitor and so which step in the viral life cycle would be targeted by this protease inhibitor would it be binding to the t-cell conversion of RNA to DNA integration to come a provirus or formation of viral proteins well we talked about how protease inhibitors would target basically viral protease which cleaves devant the viral polypeptide in two separate pieces right now it's kind of weird then is that HIV transcripts is one large mrna and so that's going to contain all the proteins that HIV requires so that that mRNA gets read by the host cell ribosome that's created into a long chain of viral polypeptide but the the viral protease is what cuts the viral polypeptide into lots of separate pieces and each one is its own individual and separate viral protein now if you can block viral protease then you can prevent this from actually being able to make functional viral proteins and at that point then you can't make new infectious particles now wouldn't cure HIV but if definitely prevent or limit the spread of infectious particles and so you guys you can knock so much HIV into sort of remission in that way they got their teeth their t-cell count can get back up and their HIV very on count could actually be undetectable at that point depending on how how well these drugs are working