Posts Tagged ‘cytokines’
immunology – an ongoing fascination
Immunology is one of those strange subjects – those who know virtually nothing about it tend to pontificate about it (I’ve experienced this), while those well-versed in it feel overwhelmed by the complexity of the human immune system and how much they still have to learn, and how each new uncovering opens up more layers of complexity.
I’ve just started to listen to The immunology podcast, some of which sounds to me as if it’s spoken in Yiddish, but it’s not the fault of the presenters – the podcast is clearly aimed at established immunologists and advanced students, with lots of in-house terminology and an assumption of knowledge not yet, and mostly never, possessed by myself. Today I was listening to episode 103 – the most recent – but it was only marginally less comprehensible than episode one (no, I haven’t listened to all the podcasts in between!). It didn’t help that I was walking through Adelaide’s pleasant parklands while listening – lots of lovely avian antics to distract me.
Anyway, let me look at more terms and concepts. Cytokines are small proteins, and there are many types, some of which are slightly familiar to me – interferons, interleukins, lymphokines, chemokines and tumour necrosis factors. Tumour necrosis means the death of tumour cells – which sounds good but often isn’t. Necrosis shouldn’t be confused with apoptosis, which is programmed cell death. More about that later, perhaps. Tumour necrosis factor (TNF) is produced mostly by ‘active’ macrophages. So what’s an active macrophage? AI tells me (I’ve been warned against using AI as a definitive source, but as a starting point it’s generally reliable) that there are two types – classically activated (M1) and alternatively activated (M2). You can see how all these bifurcations complexify the complexities, but let’s stick for now with M1, which are more clearly involved in immunity. AI again provides some basic detail:
They exhibit enhanced phagocytic capabilities, meaning they are better at engulfing and destroying microbes, and they release pro-inflammatory cytokines to recruit other immune cells to the site of infection.
So phagocytes are engulfers and destroyers of pathogens, and macrophages are BIG ones, apparently. So, clearly, anything with the -kine suffix is a small protein involved in the immune system, but not all such proteins use that suffix. Let’s look at interleukins (he said, sounding like a teacher). They’re mostly produced by white blood cells, aka leukocytes, and they act as messengers or signallers between cells involved in the immune system. It’s now known that they’re produced by many types of cells. They’re identified by numbers – IL-1, IL-6, IL-10 etc. Something I worked out today in the parklands!
But just on language, a subject I’m a little more comfortable with, the term cytokine seems to be an amalgam. Kine is a biblical term, though perhaps from later translations, referring to cattle. Perhaps the emphasis, above all, is on plurality. Cyto- is used in the term cytoplasm, and probably refers to something ‘inside’ (AI calls it anything intracellular, and it also explains ‘kine’ in terms of movement – kinesis, kinetic energy, from the Greek).
I very much remember the ‘cytokine storm’ described during the COVID-19 days, which seemed to suggest that people were being compromised, sometimes fatally, by the immune system’s reaction to the pathogen. Cytokine release syndrome (CRS) refers to this, but it can also be a response to immunotherapy. The fever that it may induce can raise a number of unforeseen problems. According to one PubMed article,
A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death.
It’s this kind of reaction that anti-vaxxers use to accuse immunologists of criminality. No doubt they’d interpret ‘deregulated immune system’ as a ‘deregulated immunology system’. But the science can point to huge successes, first with smallpox, and then with so many other potential killers – cholera, tuberculosis, polio, tetanus, diphtheria, whooping cough and influenza, to name a few.
So the same PubMed article, which focuses on COVID-19, lists a number of pro-inflammatory cytokines found in patients with the infection, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10 – IL meaning interleukin, TNF-α meaning tumour necrosis factor-alpha, IFN-γ being interferon-gamma, a type II interferon, IP-10 (interferon gamma-induced protein 10) being a chemokine or small protein involved in many immunological processes, signalling in particular, GM-CSF standing for granulocyte-macrophage colony-stimulating factor (of course), and MCP-1 (monocyte-chemoattractant protein), aka CCL2 (C-C motif ligand 2), which is a chemokine that attracts monocytes and other immune cells to sites of inflammation. A monocyte is another type of leukocyte or white blood cell – let’s see, types of leukocyte include granulocytes, monocytes and lymphocytes.
We’re just beginning, which makes me wonder, what’s more complex, our neurological system or our immune system? Probably a meaningless question.
Anyway, let’s get back to interleukins. Our genome produces more than 50 of them, and they’re vital to the effective functioning of our immune system. Deficiencies, which are rare, are known to be a factor in auto-immune diseases. Wikipedia provides detailed info on only 15 of them, so presumably there’s still more work to be done on their various functions. Some of the detailed structures and functions that are presumably known to immunologists are more or less incomprehensible to me, e.g 12-stranded beta sheet structures. To give an example, of knowledge and manipulation that’s beyond my ken:
Molecular cloning of the Interleukin 1 Beta converting enzyme is generated by the proteolytic cleavage of an inactive precursor molecule. A complementary DNA encoding protease that carries out this cleavage has been cloned. Recombinant expression enables cells to process precursor Interleukin 1 Beta to the mature form of the enzyme.
Right. There’s a mnemonic for some of the ‘important’ interleukins which might be useful, but I won’t give it here (I don’t find it useful). IL-1 is associated with fever and heat, Il-2 is a signalling molecule in T cells, affecting their growth, differentiation and function, and is important in anti-tumour cancer responses, and Il-3 is another signalling molecule, produced by T and other immune cells, influencing macrophages, mast cells (white blood cells which produce histamine and protect against various pathogens and toxins), and the odd megakaryocyte.
Megakaryocytes are, rather obviously, large. They’re present in bone marrow, where they produce platelets – colourless cell fragments important for blood clotting. Platelets circulate in the bloodstream and aggregate at injury sites. They’re also known as thrombocytes. Much of this blog piece will be like a glossary. For example, stem cells. Think of a stem that subdivides into many different parts. They can also simply divide into more of themselves. But a megakaryocyte isn’t a stem cell. Megakaryocytes are more specialised, and are derived from hematopoietic stem cells (HSCs). They arrive at being megakaryocytes ‘through a hierarchical series of progenitor cells’. I’m relying on AI for much of this. So, a HSC is a multipotent stem cell which can differentiate into all the blood cell types. So maybe I’m going beyond immunology here into the whole of biochemistry, but it’s virtually impossible to draw strict boundaries.
Anyway, I shall stop here, or pause, having loaded myself with enough preliminary information. It’s marvellous stuff, and I’ll be going on about it for quite a while….
References
https://en.wikipedia.org/wiki/Interleukin
more baffling immune system stuff
1RH2 Recombinant Human Interferon Alpha 2b – evidemment
Jacinta: We’ve been mostly educating ourselves via the NinjaNerd YouTube series on immunology, which seems very comprehensive and yet comprehensible, for beginners, and then going to other websites for details. Now getting back to cluster differentiation (CD), a commonly used immunological term. Here’s a useful definition:
The cluster of differentiation (CD) is a protocol used for the identification and investigation of cell surface molecules present on leukocytes. CD molecules often act as receptors or ligands important to the function of immune cells.
Canto: That’s useful indeed. Each CD – 4 or 8 or 25 – represents a cluster of differentiation. Differentiated from other clusters. So back to T regulatory cells, which would be differentiated into those cells that predominantly have CD4 or CD8 molecules, as well as TCRs. All to help suppress auto-immune diseases in particular.
Jacinta: So we have these T regulatory cells, as well as helper and cytotoxic T cells, all created in the thymus essentially, and then they’re distributed to the lymphoid organs – the lymph node locations include ‘the groin, armpit, behind the ears, back of the head, sides of the neck and under the jaw and chin‘. There’s also the spleen and its sinusoidal capillaries, where T cells form a surrounding layer known as the ‘periarteriolar lymphoid sheath’ (PALS), more commonly known as white pulp. A large number of T regulatory cells however remain in a thymus region known as the thymic (Hassal’s) corpuscles. They’re also distributed throughout the body – the tonsils, the respiratory tract and so on. All originating from the red bone marrow.
Canto: Well I’m still a little confused about the difference between the innate and adaptive immune systems and whether there really is any clear distinction between them (I suspect not). My own distinction so far is that the innate system is quick and not very specific and well-attuned, and the adaptive is – everything else.
Jacinta: Well, a bacterial antigen releases endotoxins which causes a massive release of inflammatory cytokines, got that?
Canto: Not particularly. Get this:
Endotoxins (lipopolysaccharides, LPS) are agents of pathogenicity of Gram-negative bacteria, implicated in the development of Gram-negative shock. Endotoxin reacts with lipopolysaccharide-sensitive cells producing endogenous mediators such as tumour necrosis factor alpha (TNFα).
That was my first stop in trying to find out what endotoxins are. Needless to say, it’s meaningless to me. Though I know that ‘endo’ means ‘from within’ as opposed to ‘exo’… I think.
Jacinta; If you look that up you’ll find it’s horribly complex. Okay the bacteria release toxins which release cytokines in reaction. There are many different kinds of cytokines, including histamines, prostaglandins and leukotrienes. Amongst other things these cytokines will impact smooth muscle cells causing vasodilation, increasing blood flow causing heat and redness. Cytokines will also contract endothelial cells, causing fluid leakage and permeability, affecting pain receptors. Bradykinins are also involved in vasodilation and increased blood flow. All this induces swelling and pain. Broadly, the four signs of inflammation are: swelling, pain, heat and redness. That answers a basic exam question. Joint immobility is a fifth sign in some extreme cases.
Canto: I’m looking at a different video, “introduction to the immune system”, because I think we need to stay on the ground floor for a while. I also think looking at language might help. For example, ‘cytokines’ feature heavily, and I was thinking that they were like some kinds of proteins or enzymes, something sub-cellular that could whizz about the body, but then I noticed that white blood cells were called leukocytes, and there were lymphocytes and phagocytes… cells! Like, complex organisms. And ‘kine’, apart from being about cattle, is where our word ‘kind’ came from, as in Kinds of Minds. So ‘cytokines’, methinks, are just the vast array of cells relating to the immune system.
Jacinta: Yes, this is good – a phagocyte is an ‘eating cell’. A lymphocyte is a type of WBC that’s involved in the immune system. T cells are lymphocytes, as are B cells. So, yes, they’re complex, gene-containing thingumies, all of them, and lymphocytes are so called because the lymph system is full of them. But note that ‘cyte’ just means ‘cell’, not necessarily of the white or immune kind.
Canto: So starting again at the beginning, with the innate and adaptive systems. So the innate system is what often causes pains and fevers, that redness and itchiness and raised temperature mentioned before – inflammation. Because of the release of cytokines, as you’ve explained.
Jacinta: Ah but here’s where it becomes confusing and unhelpful. On a website designed, I think, for high school biology students I found this:
Cytokines…. are a broad category of small proteins that are important in cell signaling. They are released by cells and affect the behavior of other cells. Cytokines include interferons, interleukins, lymphokines, and tumor necrosis factor.
So it looks like you were right in the first place. It is confusing though. Interferons are proteins, as are interleukins, and ScienceDirect, which is generally reliable, says this:
Cytokines, chemokines, and lymphokines are multifunctional immunoregulatory proteins secreted by cells of the immune system.
So we’ve both been confused, and maybe looking at language origins might confuse us more. Best just to accept what the biochemists say.
Canto: So, are we starting again, again? Let’s look at some of the cytokine types. Interferons are as mentioned, signalling proteins. But what, exactly, is meant by signalling, and what exactly is a protein? A chain of amino acids, je crois. So, signalling – that’s about sending and receiving and responding to signs of change:
Individual cells often receive many signals simultaneously, and they then integrate the information they receive into a unified action plan. But cells aren’t just targets. They also send out messages to other cells both near and far.
So far, so obvious. These signals are essentially chemical. Even neurotransmission reduces down to the chemical level. But we’ll stick with pathogens and immunity. Receivers of signals are generally called receptors, and immune-system cells often, but not always, have receptors within or sticking out of the cell membrane.
Jacinta: Interferons are so-called because they interfere with viruses and such. We’ve actually been able to create them in the lab since the 80s for treating some cancers:
Interferons are the frontline defenders in your body. A variety of cells, including white blood cells, produce interferons in response to infection and other stimuli, like cancer cells. They initiate signaling cascades by stimulating the infected cells and those nearby to produce cytokines.
Canto: But are they the frontline defenders? And they’re cytokines themselves, as aforementioned. Cytokine seems a pretty broad term.
Jacinta: Our refined or not-so-refined new definition – cytokines are types of stuff created by a variety of cells as an immune response to pathogens. As to interferons, don’t worry about it.
Canto: Too late, I’m worried. Here’s another quote:
More than twenty distinct IFN [interferon] genes and proteins have been identified in animals, including humans. They are typically divided among three classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes are important for fighting viral infections and for the regulation of the immune system.
Should we just devote the rest of our lives to interferons and forget the rest?
Jacinta: Everything’s connected to everything else. And we shouldn’t despair – we’ve learned much about the lymphatic system, for example, that we didn’t know before.
Canto: We didn’t know anything before. But yes I’m encouraged. And getting back to language, lymph is apparently Latin for ‘clear water’, which is a good start for thinking about lymphatic fluid, even if it’s anything but clear.
Jacinta: Like sea or river water I suppose. The more you look… Blame all those pesky microscopes and such. Anyway, one video describes the lymphatic system as having three main functions: 1) returning fluid to the heart: 2) helping large molecules (hormones and lipids) enter the blood: 3) immune surveillance.
Canto: Okay let’s look at all that in a bit more detail next time.
stuff about Covid-19: cytokine problems
Canto: So what are cytokines? They’re ‘signalling proteins, usually less than 80kDa in size’ – that means kilodaltons, and it refers to molecular mass. Proteins have a huge variety of shapes and sizes, the largest being titin, with a mass of 3,816,188.13 Da. I don’t know why they don’t keep to kilodaltons. I presume the daltons measurement is in memory of the pioneering British chemist John Dalton, a truly inspiring character. Cytokines are quite small proteins, I think. Or peptides, which are described on other science sites as not being proteins, or not quite, which is confusing.
Jacinta: We’re looking at a ScienceDirect website which is pretty technical, but it says cytokines regulate many biological functions including those related to innate and acquired immunity. Here’s its ‘operational definition’:
Cytokines can be defined operationally as polypeptides secreted by leukocytes and other cells that act principally on hematopoietic cells, the effects of which include modulation of immune and inflammatory responses.
So peptides are short strings of amino acids, and proteins are longer strings of amino acids, so polypeptides are apparently more than just peptides but not quite proteins. Very weird. Leukocytes are white blood cells, of which there are three main types (I think): monocytes, lymphocytes (T cells and B cells) and granulocytes (neutrophils, eosinophils and basophils). Leukocytes are made in our bone marrow and are found in our blood and lymph. I’d love to learn about lymph one day.
Canto: So leukocytes are part of our immune system, as are the cytokines they secrete. Hematopoietic cells – always worth breaking things down: hema, or haema, always refers to blood, and poiesis, from ancient Greek, essentially means production or bringing into being. Presumably, then, these hematopoietic cells exist in the bone marrow, where they produce leukocytes. And yet… that all seems to mean that cytokines are secreted (and presumably produced) by leukocytes to act on hematopoietic cells that produce leukocytes… It seems a bit circular to me.
Jacinta: Certainly complex. Let’s barge on. The ScienceDirect site has it that cytokines are secreted by many cell types, often at high concentrations, and are mostly involved in cell-to-cell interactions with neighbouring cells. This is called paracrine signalling, as opposed to other forms of signalling (endocrine, juxtacrine and autocrine). However, cytokines can sometimes use those other forms. There are many different groups of cytokines, usually named for their most significant effects, as we see them, but they’re actually pleiotropic, meaning they have each a variety of functions, and those functions can be mediated by other cytokine groups. So, certainly complex, but in terms of their function in response to airways diseases…
Canto: But now I’m hearing that Covid-19 isn’t necessarily an airways disease, or only an airways disease. It may affect the brain and the nervous system, the kidneys, the heart, the blood…
Jacinta: Hmmm, so much more to explore, before we all die. But knowledge is power, the more we know, the more we can defend ourselves. Let’s all be Popperian optimists and rise to the challenge. Here’s an overview, from a 2009 article on cytokines as related to asthma and COPD:
The major classes of cytokines include: pro- and anti-inflammatory cytokines, cytokines of neutrophil and eosinophil recruitment and activation, cytokines derived from T-helper (Th) and T-regulatory (Tregs) cells, and cytokines of T-cell recruitment and growth factors.
The cells mentioned are all leukocytes. But the storm of cytokines may well be causative of those other symptoms found in Covid-19 sufferers, such as blood clots. A very recent article in the Lancet has this to say in reference to what we’re seeing:
the overproduction of early response proinflammatory cytokines (tumour necrosis factor [TNF], IL-6, and IL-1β) results in what has been described as a cytokine storm, leading to an increased risk of vascular hyperpermeability, multiorgan failure, and eventually death when the high cytokine concentrations are unabated over time. Therefore, therapeutic strategies under investigation are targeting the overactive cytokine response with anticytokine therapies or immunomodulators, but this must be balanced with maintaining an adequate inflammatory response for pathogen clearance.
Canto: Wow, I suppose one thing we’ll be learning fast from this pandemic will be a lot more about cytokine production and how it can be abated without risk to the immune system. I wonder if there are any ‘anticytokine therapies’ at present?
Jacinta: Well I’ve read this Lancet article and I can’t pretend to comprehend all that’s in it, but of course it tries to address all we’re concerned about here so I’m going to try to explain it in my way. Hospitalised Covid-19 patients are presenting with pneumonia, ARDS and other respiratory conditions, and sepsis. Sepsis is a broad term, referring to an unbalanced blood immune response which, at its worst, can lead to multiple organ failure. Vascular hyperpermeability, mentioned above, is defined as ‘the excessive leakage of fluid and proteins from blood vessels to the interstitial space‘, being the fluid-filled space around tissue cells. The protease thrombin, which is apparently a coagulant (among other things) and not itself a cytokine, is in normal circumstances tightly regulated in the body by multiple factors, all of which can be impaired by hyperinflammatory conditions. The procoagulant-anticoagulant balance is disrupted, which can lead to microthrombosis and ‘disseminated intravascular coagulation’. Which I think is self-explanatory, and not good. The article refers to ‘raised d-dimer concentrations’ which has to do with fibrin, a fibrous protein involved in blood-clotting. The difficulty is that treatment with ‘endogenous anticoagulants’ has its dangers, shown in previous negative trials. There’s this important factor in respiratory physiology called the ventilation/perfusion (V/Q) ratio, with V being the measure of air getting to the alveoli, and Q the measure of blood getting to the alveoli. A mismatch there can affect the possibility of venous thromboembolism – blood clots, to oversimplify. What this forbiddingly technical Lancet article is suggesting, finally, is that studies conducted on murine [rat/mouse] models of PAR-1 antagonists (PAR-1 being protease-activated receptor, the main thrombin receptor mediating platelet aggregation) have shown some promise, and need to be further investigated tout de suite. Here are the authors’ final words:
Targeting thrombin, coagulation factor Xa or PAR-1, might therefore be an attractive approach to reduce SARS-CoV-2 microthrombosis, lung injury, and associated poor outcomes.
References
https://en.wikipedia.org/wiki/John_Dalton
https://www.sciencedirect.com/topics/neuroscience/cytokines
https://www.medicalnewstoday.com/articles/326701
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/leukocyte
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30216-2/fulltext
Covid19: world progress, cytokine storms, our plans
Canto: So while we need to be worried about – and to know something about – the cytokine storm that the Covid19 infection can lead to (and we’ll learn about that soon), there’s also a storm of activity on the SARS-CoV-2-fighting front.
Jacinta: Yes, intravenous zinc was talked about in the Medcram series as an effective tool in fighting viral pneumonia, and a world-first trial is being conducted by Austin Health and Melbourne University to test its effectiveness for Covid-19 sufferers with respiratory problems. We’re still catching up on the Medcram series, and update 52 talks of the drug ivermectin, already on the WHO list of essential medicines. The WHO website, incidentally, is promoting a ‘solidarity’ clinical trial for Covid-19 treatments, involving, singly or in combination, remdesivir, hydroxychloraquine, lopinavir, ritonavir and interferon beta-1a. So that gives some idea of the work that’s going on to fight symptoms and reduce the death rate.
Canto: And, you know, I’ve been feeling guilty about singling out the USA as the worst-case scenario all round. It’s not actually so. It’s not fair to look at total figures and point out that the USA tops the list for Covid19 fatalities, and draw calamitous conclusions. You have to take into account its much larger population compared, for example, to number two on the list, Spain. The US has suffered about 2.5 times the fatalities of Spain, but it has about 7 times the population. In fact, if you look at fatalities as a proportion of population, there are many countries worse off than the USA – namely Spain, Italy, France, the UK, Belgium (the worst hit), the Netherlands, Switzerland, Ireland and Sweden. All European countries, notably.
Jacinta: Yes and I’m sure they’ll all have their particular stories to tell about why this is happening to them, and will be wanting to learn lessons from Taiwan, Hong Kong, South Korea, and even our big faraway island, but I really want to look at solutions, in terms of eradicating the virus, or blocking it, or building up our immunity. Having said that, flattening the curve, and reducing fatalities, is a primary focus, which means continuing the physical distancing and looking for ways to keep economies running while this goes on. In spite of patches of civil libertarian activity here and there, the vast majority of our global population is on the same page with this, I think.
Canto: Well I’m looking at an Axios article from the Johns Hopkins website. It compares global performance under Covid19 to a mock pandemic exercise, Event 201, conducted some six months ago. They’ve found some positives and some negatives in their analysis. Positives – a greater degree of compliance with physical distancing measures than expected, ‘the degree of surge capacity augmentation in the health care system which has been possible’, and the rapid growth of international collaboration among scientists, leading to a quickened progress of trials for possible treatments. Negative – disparate and often contradictory messages from authorities – mostly political authorities – leading to confusion and distrust of governments and other institutions. This is partially explained by the complexity of the virus itself, which has made it difficult to characterise to the general public, and to be fully understood by non-medical authorities, such as political leaders.
Jacinta: It’s a weird situation, as there’s no end in sight, everyone’s worried about ending restrictions too soon, yet everyone’s worried about the economy, and those countries, like Australia, that are heading towards winter, are bracing for heightened problems, while northern hemisphere countries are hoping for summer’s relief but worried about the autumn when it might be hard to cope with a second outbreak, should it come. And medicos are warning that expectations of a vaccine in eighteen months might be overly optimistic. But I want to be optimistic – I want to look at anything that’ll reduce symptoms and save lives. One treatment, among many others it should be noted, is hydroxychloraquine, which is being given so much of a bad press, because of its being over-hyped by a Trump administration intent on getting political points for a silver-bullet cure. There have already been a number of small, less-than-gold-standard studies, some in which the drug is combined with the antibiotic azithromycin, and the results appear to be all over the place. We’re still awaiting the results of randomised, placebo-controlled, double-blinded studies, which are under way.
Canto: I note that a couple of reports on chloraquine and hydroxychloraquine on the JAMA website have been taken down, I suspect because of all the politicising. That’s a shame. Anyway I mentioned the cytokine storm at the beginning of this post, so I’ll try to comprehend it. A clue to the meaning comes in this mid-March article on the Lancet website. In an early sentence it mentions ‘cytokine storm syndrome’, and in the following sentence refers to the treatment of ‘hyperinflammation’. It seems the two terms are interchangeable. Another term, in the very next sentence, is ‘a fulminant and fatal hypercytokinaemia’….
Jacinta: Sounds like they’re just showing off.
Canto: Please don’t say that about our frontline covidtroops. Okay, a better site for understanding cytokines and their storms is this from New Scientist. As we’ve guessed, it’s an over-reaction of the immune system, sometimes fatal. Cytokines are small proteins, produced throughout the body, which trigger inflammation as an immune response. Sometimes the intensity of the cytokine response results in hyperinflammation. So you might say the cytokine storm is the cause and hyperinflammation the effect.
Jacinta: So this raises questions. For example, why do some have what seems an over-production of these cytokines and others don’t, in response to SARS-CoV-2 in particular? And what do these cytokines actually do to cause inflammation?
Canto: You’re asking me? Well, it’s conjectured that younger people don’t have the developed immune system that produces all these cytokines, and that’s why you don’t see symptoms. But that raises the question – do others have over-developed immune systems, but maybe only for this particular virus? Is there a general goldilocks level?
Jacinta: And is there a way of distinguishing between those who succumb to the hyperinflammation, which in turn can cause acute respiratory distress syndrome (ARDS), and those who succumb to the virus itself? Or is it always the immune response that does people in?
Canto: I don’t think so. If the immune response doesn’t work at all, I suspect the virus will spread like a cancer to the rest of the body?
Jacinta: That can’t be right. That’d mean those kids who don’t suffer the cytokine storm, or any immune reaction, would remain infected until it spread through their bodies and they dropped dead. That definitely isn’t happening.
Canto: No, you’re right – they’re developing antibodies, presumably, (and that’s a whole other story), without going through much in the way of suffering. In fact, children’s apparent immunity to the virus is something of a mystery that demands further research. If everyone could develop that kind of immunity…
Jacinta: So many questions we can’t answer. I mean, not just the myriad questions we, as dilettantes and autodidacts, can’t answer, but the fewer but many questions epidemiologists, virologists and ICU workers can’t answer. But I propose that we continue to try and educate ourselves and explore, in our feeble but earnest way. I propose that we dedicate this blog, for the foreseeable, to exploring terms and conditions, so to speak, and treatments, such as ‘cytokine’, ‘ACE-2’, ‘hypoxia’ and ‘quercetin’ and how they relate to or are affected by the Covid-19 infection. Like putting pieces together in a jigsaw puzzle, sort of. It might help us being overwhelmed by the whole picture.
Canto: Okay, let’s try it.
References
Coronavirus pandemic update 52, Medcram youtube video
https://coronavirus.jhu.edu/news
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext
https://www.newscientist.com/term/cytokine-storm/
https://www.centerforhealthsecurity.org/event201/
https://jamanetwork.com/journals/jama/pages/coronavirus-alert