Good long term immunity

oh you're most welcome to this talk it's Sunday evening the 30th of May now there's been a lot of pessimism even even among sort of senior authority figures about immunity to SARS coronavirus 2 after infection and vaccination not lasting for very long and a lot of that was based on the idea that the seasonal coronavirus is this four seasonal coronaviruses that cause common cold symptoms the immunity from those actually only does last for six to 12 months but I think we're getting some much more optimistic data coming out now indicating that my long-held view that there's likely to be long-lived immunity after SARS coronavirus 2 is starting to be supported by the data now the first paper we want to look at briefly is this one duration of antibody response after severe acute respiratory syndrome now this came out in 2007 so of course this is talking about SARS coronavirus one the pandemic uh well it well it was a pandemic it spread to a few countries in 2003 nothing like on the scale of this one of course so duration of antibody response after severe acute respiratory syndrome 2007. 176 uh subjects saw specific antibodies were maintained for an average of two years remember this is SARS coronavirus one from the 2003 outbreak significant reduction in immunoglobulin G in the third year so from that it's looking like the immunity lasts for about two years from SARS coronavirus 1 from the 2003 outbreak so that was the first paper and people have focused a lot on this uh to be pessimistic about the current outbreak but um this is from the British medical journal so this is the next paper we're looking at here that's this one do many people have pre-existing immunity quite a fascinating article actually talks about a whole range of things related to immunity um well worth the read the link is there just click on it but the thing I wanted to point out from this article is that it's um as well as talking about the antibody response it's talking about the cellular response but T-cell studies allow for a substantially different more optimistic interpretation compared to just looking at antibodies is what this uh this paper talks about so let's go on and look specifically now at one of these papers and that's uh this one so in this paper here so let's look at this one now now this actually came out in 2020. um SARS coronavirus to specific T cell mediated antibodies now remember these T cells are the T lymphocytes just a quick revise we've done this quite a few times but the the white cells the protective cells are the lymphocytes one type of white cell the lymphocyte so there's two sources the large and there's the small the larger the natural killer cells that we've looked at before that kill virally infected cells the smaller divided into the B and the T lymphocytes so we're talking about the T lymphocytes here so the small lymphocytes of the B and the T lymphocytes and the T are important because there's T helpers T suppressors and T cytotoxic cells so it's the T helper cells that help the B cells to make the antibodies that's the way it works so we're talking about these T cells that they're a type of white blood cell a type of leukocyte anyway back to the paper now only 36 patients involved in this but published in nature in in 2020. now in these 36 patients in all of these individuals we found CD4 and cd8 cells that recognize multiple regions of the end Protein that's a bit complicated already but the CD4 and cd8 are both types of t lymphocyte both types of two lymphocyte the CD4 actually the T helper cells and the cd8 are actually the T cytotoxic cells anyway in patients that have been infected with SARS coronavirus 2. they found these cells that were activated to multiple regions of the the N protein the nucleoplasmid protein um more on that in a minute coronavirus nucleoplasmid n structure protein that forms complexes with genomic RNA so the genomic RNA is the RNA of the virus so basically what you've got with with the SARS coronavirus is you've got the virus there and you've got your strand of RNA in there and then you've got your Spike proteins there so the nucleoplasmid proteins are associated with the RNA in the nucleus well it's not really nucleus is the center of the cell then these are the spike proteins here and these are the membrane proteins in the membrane roundabout there so basically we've got these three lots of protein Spike protein membrane proteins and then these internal ones the nucleoplasmid proteins now studies could look at any of these but different studies tend to look at different ones because it's easier to analyze one particular aspect of the immune response but these are all immune responses generated to the antigens which are the virus whether it's the N antigens the S antigens or the M antigens the nucleoplasmid the spike or the membrane antigens they're all parts of the virus that your immune system recognizes as being foreign of course the immune system is just the most mind-blowing system it's quite incredible um so anyway these 36 patients um so coronavis nuclear plasma is structural protein so we said that patients so what they found is that all 36 patients all of these 36 patients in the months after infection had these activated T cells the CD4 helper cells that will help the B cells to make the antibodies and the cd8 T cells that will directly kill virally infected cells in fact I've got a diagram here from my physiology notes book so um these are actual uh I've actually enabled these as natural killer cells but the same would apply to T cytotoxic lymphocytes so they can directly kill sometimes cancer cells and they can directly cure virally infected cells so this natural killer cell or the two cytotoxic cell they work in the same way comes next to the virally infected cell drops these proteins called perforins on it and these perforate the cell let water into the cell and this cell is basically killed and as that cell is killed the viruses are killed with it so that's the way the uh the T cytotoxic and the NK cells are working but anyway so the fact they found these cells were there and they got rid of the virus they were effective and they were still there after the infection but then and this this is the this is the this is the most encouraging thing I'm going to tell you today is remarkably encouraging they found 23 patients this is dustedly done in Singapore so to find patients that 36 patients that they're able to analyze that are infected with the um SARS coronavirus too no big deal we've got plenty of those but then they found out 23 patients who'd suffered from SARS a severe acute respiratory syndrome in 2003 with the SARS coronavirus one infection so these are people that were infected with a similar virus this this study was done in 2020 so that was 17 years before that 23 patients possessed long-lasting memory T cells that were still reactive 17 years later the infection was in 2003 the tests were done in 2020 and these cells the helper cells and the killer cells were still there so SARS coronavirus one now no longer exists in the world but if these patients were re-infected with it they would still be immune to it or have a large level of immunity to it 17 years later so that's the paper there don't take my word for it read it for yourself it's all there and uh a very interesting uh very interesting read if a bit if a bit detailed in places um right back on the right screen yeah these T cells display robust cross reactivity to the nuclear plasmid protein of SARS coronavirus 2. in other words people that have had SARS coronavirus one are likely to have a large degree of immunity to SARS coronavirus to cross-reactivity now I think from memory there was only about 80 000 people had the infection in 2003 because it was contained but those 80 000 people would be immune to SARS coronavirus 2 or largely immune to size coronavirus to 17 years later on this is why I'm optimistic that the immunity we're now generating to SARS coronavirus 2 is going to be long-lived but more on that in a minute when I give you the precise uh evidence for that epitope characteristic of specific T Cell cells shows the recognition of protein fragments that are conserved amongst animal beta coronaviruses now of course SARS coronavirus 2 is a beta type Coronavirus now the epitope is the part of the virus that the immune system recognizes as being foreign it's the antigen the epitope and what this is saying is that these cells these immune cells that regenerated in response to SARS coronavirus one recognize protein fragments on many different types when it says it's conserved that's an evolutionary term it means it's been conserved through viral evolution and it means that it occurs in many different animal coronaviruses so presumably out there in the animal kingdom there's Untold or I don't know hundreds hundreds of different types of coronaviruses what this is saying is that the immunity from SARS coronavirus one will extend against a wide range of those but they are different to the common cold coronaviruses that caused the common cold so the animal coronaviruses that we have at the moment are the SARS coronavirus one well it's not there anymore but the SARS coronavirus too and of course the Middle East Respiratory Syndrome virus of the three but were others to jump from the Animal Kingdom to humans or however it got here um then it's presumed that there will be a degree of immunity in those people that suffer from SARS coronavirus one because the proteins are highly conserved across different viruses in the animal uh in the animal coronavirus groupings populations of coronaviruses so next paper um persistent cellular immunity now this one actually is a preprint so that is uh this one here um but it looks like a pretty well written paper so I'm going to tell you about it anyway um I've read it I'm not a good peer reviewer but it looks okay to me now this is persistent cellular immunity in SARS coronavirus infection and this is looking particularly at A T Cell immunity this particular paper so cellular and hormonal immune response to infection now what this means is when you have SARS coronavirus II you're going to develop a cellular response that's the lymphocytes the B and the T cells that's the cellular immunity but you also develop a humeral immunity now humor humors relate to the fluids in the body um so we talk about being in Good Humor that goes on Old theories relating to fluids in the body but humors still mean related to the fluids in the body so humeral immunity is the immunity in the fluids of the body that is in the antibodies that are circulating throughout the blood and the tissue fluids so in other words the infection with SARS coronavirus 2 causes a cellular response and a humeral response an antibody response that's what that means antibody responses include most of the structural proteins expressed by the virus so we know that there's different as we've said with different proteins on the viruses the nucleoplasmid there's the spike there's the membrane antibodies to all of these are made specific antibodies that fit the reciprocal shape of the specific proteins that make up the virus so antibody responses include most of the structural proteins expressed so it's a polyclonal antibody response in response to the different components of the proteome of the virus neutralizing antibodies directly prior uh directly primarily to the receptor binding domain of the spike protein so we knew that we know those neutralizing antibodies um that they fit onto the spike protein and when the antibody fits onto the spike protein so that's the spike protein there and the sum the some antibody sticking onto it like that then that means it can't fit into its receptor site the antibody gets in the way whereas if the antibodies not there the neutralized antibodies not there it fits in and you get the infection so the neutralizing antibodies mostly affecting the spike protein um but there's other antibodies as well and what these other antibodies will do is they'll actually agglutinate the the viral particles so they will Clump a lot of them all together because the antibodies are sticky and they'll Clump a lot of the viruses together you end up with a clump of hundreds or thousands of viruses all clumped together and then one of these big cells that eat fragments so they've got one of the phagocytes one of the macrophages can come along and eat it all together it's said that antibodies prepare the food for the phagocyte stable the eating cells um so it clumps them all together so two ways the antibodies are getting rid of it um but moving on neutralizing antibodies must have said that but lymphopenia is a prominent feature of severe infection now lymphocytosis would be an increase in the number of lymphocytes in the blood a lymphopenia would be a reduction in the amount of lymphocytes in the blood so when people have severe um severe covered severe infection caused by SARS coronavirus too they get a lymphopenia the number of lymphocytes goes down now it's the lymphocytes that combat in the infection so you'd expect the number of lymphocytes to go up but actually what happens is these blood tests that measure a lymphopenia a reduction in the number of lymphocytes in the blood they're measuring just that the number of lymphocytes in the blood because the lymphocytes are needed in the tissues to kill the infection the lymphocytes move from the blood into the tissues therefore the number of lymphocytes in the blood goes down it's quite clever really so people if people have a lymphopenia during a viral infection that's an indicator that these lymphocytes are essential for fighting the viral infection because they moved into the tissues to do their job to do the business of getting rid of the virus so during acute infection T cells display highly activated cytotoxic phenotype this is just a scientific way of saying that the form of the cells and the function of the cells is to be cytotoxic and to kill virally infected cells as we showed in that diagram there virally infected cells are eliminated these cells develop a phenotype a way of a structure and a function which is precise to killing cells of course is exactly what we want then the virus can't spread around the body a convalescent plasma Harbor's poly-functional SARS coronavirus 2 T cells so when people get better they have many functional T cells that have got rid of this virus and they remain in the blood for a while but then these cells often display a stem like memory phenotype again phenotype is the structure and function that you actually see stem-like means it's related to stem cells so related to stem cells and stem cells are any cell which is capable of further differentiation now I notice I'm getting a bit complicated today but I know quite a lot of you like this kind of stuff so let's just look at this in a little more detail so this is from my physiology book so here we see that um this particular um this particular lymphocyte is detected uh this this is a bacteria of course the vice will be way smaller now what happens is that the particular lymphocyte here that is detected that that is correct for this particular type of bacteria or in the case of SARS coronavirus 2 of course a virus then what happens is this cell divides and it divides into two populations this population here divides and divides again and divides again and divides again and divides again to make a huge population of these and these these cells in this case are B cells but these are plasma cells billions of them and these produce the antibodies but we get the same thing with T cells we get proliferation of T cells as well and whether it's B cells or T cells this cell also divides into another cell here and this cell here remembers exactly how to combat that virus or bacteria but it's not functional but it does divide and it divides into a group of cells like this and these this group of cells here these are the memory cells they remember how to attack this and then if the infection comes along again some of these can divide again into more that produce a population of the effector cells so we have these memory stem type cells in the B and T uh response the immune system is absolutely incredible and uh these have uh cross reactivity with seasonal common cold coronaviruses now why is it that some people get severe infection with SARS coronavirus too and other people get less severe infection well we know about all the risk factors and the comorbidities but even so you can get someone with the same comorbid it as the same age same sex one gets bad disease one doesn't get bad disease the answer may be that the one that doesn't get as bad disease had infection with a seasonal coronavirus three months ago had a common cold with it and had a degree of immunity because they were still within that six to 12 months where the immunity lasts after the SARS uh after the um the common cold coronaviruses so cross reactivity could be a factor in determining that and that the authors do say it could be associated with the amount of course of disease coronavirus levels persist persistent immunity now for seasonal coronaviruses immunity there is only lasting for six to 12 months we know that but we've seen that with SARS coronavirus one it lasts for 17 years immune response is uh in recovered individuals that can measure the T Cell response so that's what they did in this study and they had two they had paired samples of people they looked at them 1.3 months after the infection in 6.1 months after the infection so they're able to compare the infection 1.3 months after the infection and 6.1 months after the infection 41 people males and females variety of Ages various severities of disease but most of the diseases were fairly mild and recovered individuals shows persistent poly-functional SARS coronavirus II antigen specific memory so they're able to see these memory cells in the blood and that's important to notice that at this stage they were seeing these cells in the blood and that could contribute to a rapid recall responsive for a reinfected in other words it would give immunity in recovered individuals so enduring immune alteration numbers in the blood of CD4 helper cells cd8 T cells cytotoxic cells in the blood up to six months after infection so it's looking good for six months now uh summary here is broader reactive and highly functional memory T Cell response yes that occurred persisted six months after the infection we know that but of course we haven't had too much time to work it all out yet enjoying immune alterations in CD4 and cd8 cell compartments in other words this is talking about the memory compartment so there were memory cells that they detected in the blood uh but specific circulating T Cell numbers goes down over six months so the amounts of these specific T cells that particularly fight the SARS coronavirus 2 does go down after six months does this mean that the infection might only last for six months the answer is no because turns out that these memory cells only stay in the blood for a few months then these memory cells migrate into the bone marrow you migrate into the bone marrow and they stay in the bone marrow and if they're living in the bone marrow of course you can't detect them in the blood now there's two sorts of bone marrow there's yellow bone marrow and red bone marrow the the long bones like your femur and your humerus and your radius and your ulna they contain mostly mostly yellow bone marrow especially in the middle they do have some red bone marrow at the epiphysis at the end flat bones like your sternum your skull your pelvis very rich in red bone marrow so um that is where the cells reside but how do you find out if these cells are in the bone marrow well the only way to do that is to can you often do it through the sternum stick a needle through that and suck out some of the bone marrow so a very invasive painful procedure well it depends who does it local anesthetic but you know it's still it's still it's a traumatic procedure you know if someone says you need a blood sample then that's one thing but if you're going to stick something into bone marrow that's something else so that's why this piece of research is particularly uh appreciated and impressive and this is uh SARS coronavirus 2 infection in Juice long-lived bone marrow plasma cells in humans now the plasma cells are the B cells the B lymphocytes and of course the only way to know this is because noble people and there's no other way to put it noble people allowed their bone marrow to be sampled so the the one we were looking at before was T-cell response we've seen that has longevity in the blood but that's Limited now this paper here is not looking for the presence of T cells in the bone marrow if it look for them I suspect it would find them but we can only report what the paper's saying it was looking for the presence of long-lived uh plasma cells which are the B cells that actually make the antibodies so this particular study was only actually looking for the presence of the um B cells the B lymphocytes but that's what we've got so um but of course that's part of it it would be very surprising if the B cells persisted in the T didn't but it's just what they were looking for so we can only say what it says but it's very encouraging um long-lived bone marrow plasma memory cells were found in the bone marrow convalescent individuals have a significant lower risk of reinfection we know that patients who experienced mild infection there were 77 of them Spike antibodies decline rapidly in the first four months after infection then more gradually over the following seven months so the amount of antibodies in the blood are going down fairly quickly for four months and then going down more slowly for the next seven months but the time you get to about 11 months though there's not it's it's the the numbers have dropped off quite significantly and they can be hard to detect so that's looking bad so um Spike protein antibodies decline rapidly of the first four months then more gradually over the next seven months remaining detectable at least 11 months after the infection but sometimes a year after the infection you might not detect them depending how sensitive your detection is so this looks pessimistic but actually it's not because if you think about it today I've probably been exposed to 30 or 40 viruses a dozen types of bacteria so every day we're exposed to these viruses and we're making antibodies most of the time we don't get sick because we make the immune response before we get sick but if we had antibodies circulating in our blood to all of the viruses and all of the bacteria we've ever been exposed to in our life then our blood will be thick sludge and we'd all die of thrombosis or something um so you can't keep high levels of antibodies for everything in the blood that will be ridiculous so it's not surprising in fact I would 100 expect the antibodies to go down it's exactly what you'd expect but bone marrow aspirate and they were looking at um Spike specific uh bone marrow plasma cells so looking at one particular type of uh so in other words the plasma cells that knew how to make the antibodies to the spike protein is what they're looking at you can't look at everything in one study that's what they looked at 18 stars coronavirus two convolution patients seven to eight months after infection uh so seven to eight months after the infection they're looking at the bone marrow five patients it looks over 11 months after the infection so they're looking at Patients seven to eight months and eleven months after the infection now some patients were vaccinated towards the end of this um experiment so that they dropped out this is looking at natural immunity uh it starts growing advice to infection we're looking at here so um seven to eight months and then five patients at 11 months numbers don't sound good but if they all have it then that's pretty promising and they did uh so seven to eight months there was no plasma uh blast cells blast cells are cells that produce something in this case they produce antibodies so seven to eight months um there was no specific um B lymphocytes that's what that's what that's saying no specific B lymphocytes blast cells that make the antibodies in the plasma they weren't in the plasma anymore um there are still some antibodies that lingered on because antibodies can Linger on for a few months but the cells weren't there but they did find the cells in the uh bone marrow now as well as that here they had 11 patients who had not had the infection who also volunteered for bone marrow samples and none of that none of those had these cells but the ones who these patients here seven to eight months after infection and uh some a few patients 11 months after infection they had these specific bone marrow plasma cells in other words these B lymphocytes they had that in their bone marrow just uh waiting in case it had to do its job again they were there there waiting in the bone marrow with the memory of exactly how to combat this virus quite amazing quite amazing the immune system we demonstrated the direct quotes we demonstrated that s binding bone marrow plasma cells in other words the B lymphocytes are quiescent they're sitting there quietly indicating that they are part of a long-lived compartment a long-lived immune compartment in the bone marrow overall we show that SARS coronavirus to infection induces a robust antigen specific long-lived humeral response in humans because these cells can make the antibodies that go into the body humus into the fluids and will confer immunity and because it's true of the B cells I would imagine if they looked it would be true of the T cells as well it would be really quite unimaginable that you would have memory B cells without memory T cells in fact really you must have because it's the T cells that tell the B cells how to make the antibodies so you must have they must be there it's just that this study didn't look for them specifically so um seven to eight months and 11 months after infection with SARS coronavirus 2 um the cells are there in the bone marrow and no reason why they shouldn't go away they can just sit there in the bone marrow for years as the cells in SARS coronavirus 2 sat there for 17 years that's why I'm optimistic that we're going to get rid of this virus right just a couple of words from the pundits before we finish um Scott Hennessy immunologist University of Pennsylvania the papers are consistent with the growing body of literature that suggests that immunity are listed by infection and vaccination for saskaran advice 2 appears to be long live so he's happy that this will apply to vaccination induced immunity as well as infection induced immunity um what seems to be particularly effective is the infection followed by the vaccine that seems to be particularly good immune response the reason the reason we the reason we get infected with common coronavirus common common coronal devices repetitively that's the common cold coronaviruses throughout life might have much more to do with the variation of these viruses rather than the immunity in other words the common cold coronaviruses mutate much much quicker than SARS coronavirus one and SARS coronavirus two notwithstanding the mutants that we have that is still a true statement immunologist Rockefeller New York people who are infected and get vaccinated really have a terrific response a terrific set of antibodies because they continue to evolve their antibodies because the cells are hiding in the bone marrow and can continue to make antibodies I expect that they will last for a long time long time to me don't don't know I put words in his mouth but we're talking years a booster dose is going to be necessary probably for those who've only been vaccinated so they might need a third dose to get their immunity up but people have had the infection and then had the vaccine would probably be immune for I think for a decade or two or three but we're going to know about a third dose pretty soon will a third dose give immunity which is comparable to natural immunity well with other vaccines it does right if you watched that well done because I know that's quite scientific but let me just give you a quick summary because the immunity to SARS coronavirus one is long-lived and I think we've given evidence now that the community the immunity to SARS coronavirus 2 is also going to be long-lived as more and more people become immune I think this infection can be eradicated from the world providing we get vaccines out to everyone that needs it um or additional vaccines to the people or one additional vaccine perhaps to people that already been infected so cause for optimism in the medium term it's going to take a few years a few seasons to get rid of it now I might be wrong um some senior doctors in the UK have said this is going to become endemic indefinitely um but I think the evidence is starting to accumulate in support of my position that we can get rid of this virus after a few seasons don't know how many but a few seasons so I am hopeful for that and if you've watched this video all the way through thank you for watching we'll have an easier one next time and use one oh and I've got a report from Susan in Australia for the next video as well so tune in for that thank you for watching

Channel: Dr. John Campbell

Views: 319,259

Keywords: physiology, nursing, NCLEX, health, disease, biology, medicine, nurse education, medical education, pathophysiology, campbell, human biology, human body

Id: mzOf6Cj3T-8

Length: 33min 16sec (1996 seconds)

Published: Sun May 30 2021