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Posts Tagged ‘immunity

Interferons – they’re there to help

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some human interferon looks something like this, according to someone

When I first heard of interferon (singular), I thought it was a drug, some sort of miracle drug being touted as a cure-all. I had no idea. Recently I’ve heard that it, or they, are part of our innate immune system, which is different from our adaptive immune system, though what the differences are I have no idea. Again. So, it’s learning time.

Wikipedia vastly increases my knowledge with its first sentence on interferons (duh, I wonder why people don’t use it more):

Interferons … are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

Host cells are the cells of larger organisms (such as ourselves) that ‘host’, willingly or not, viruses and other bugs, or organelles, whatever. Signalling proteins are explained, somewhat, in the second quoted sentence.

Anyway, interferons belong to the larger class of proteins known as cytokines, which I’ve heard of in relation to the ‘cytokine storm’, a reaction or over-reaction to viruses such as SARS-Cov2, but they do more than just signal, they interfere, as the name suggests. In fact they have multiple functions, such as ‘upregulating antigen presentation’. An antigen, as I almost recall, is a molecular structure, part of a pathogen that can be bound by an antigen-specific antibody. Antigen presentation is – well it’s too complex to explain here, though I feel I need to arm myself with as much immunological knowledge as possible against the misinformation out there.

So IFNs, as they’re known, come in 3 types, alpha, beta and gamma, based on the receptors through which they signal. They form part of the innate immune system, generally speaking, but there are in fact complex interactions between the innate and adaptive immune systems which immunologists are still trying to work out. I should point out here that my first understanding of interferon was no doubt based on a breakthrough in the eighties when interferons were created in the lab to treat certain types of cancer, and later in the treatment of hepatitis, multiple sclerosis and other conditions, though many of these interferon medications have been superseded by newer treatments with fewer side-effects.

My question arose through watching a Medcram video – update 128 – ‘innate immunity, interferon and Covid-19 in children’. I’ve used these updates in the past to reduce my general ignorance of immunology, virology and the like, but I’ve not watched any for a while. So, having just perused the Wikipedia article on IFNs and finding it way too complex for my small brain, I’ll base the rest of this piece on Dr Seheult’s Medcram presentation.

So, the innate and adaptive immune systems are presented pictorially. The innate system starts with a myeloid progenitor cell. These cells are described in ScienceDirect as ‘the precursors of red blood cells, platelets, granulocytes…’ and a bunch of other cells. In the Medcram pictorial, arrows from the myeloid progenitor cell lead to five other cell types – mast cells, basophils, neutrophils, monocytes and eosinophils. Arrows from the monocytes then lead to macrophages and dendritic cells. What do these have to with IFNs? I’m trying to find out.

Mast cells are types of granulocyte, and they contain granules ‘rich in histamine [which induces inflammation] and heparin [which prevents blood clotting]’. They play an important protective role in the immune and neuroimmune systems.

Basophils are also granulocytes, and a type of white blood cell (leukocyte). They’re the rarest and largest type of granulocyte, and are an inflammatory agent.

A neutrophil is ‘a type of immune cell that is one of the first cell types to travel to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of white blood cell, a type of granulocyte, and a type of phagocyte’ (National Cancer Institute – USA).

Eusinophils ‘are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates’ (Wikipedia).

A monocyte is ‘a type of immune cell that is made in the bone marrow and travels through the blood to tissues in the body where it becomes a macrophage or a dendritic cell. Macrophages surround and kill microorganisms, ingest foreign material, remove dead cells, and boost immune responses. During inflammation, dendritic cells boost immune responses by showing antigens on their surface to other cells of the immune system. A monocyte is a type of white blood cell and a type of phagocyte’ (National Cancer Institute).

Now to return to the Medcram video, which tells me that the innate immune system includes macrophages and killer T cells (which are also part of the adaptive immune system). These combine to phagocytise, or ingest, viral or pathogenic material. This innate immune system is generally very strong in childhood and gets weaker with age. Interferon is a product of this innate system. Dr Seheult cites a recent article from Nature Biotechnology with the revealing title ‘Pre-activated antiviral innate immunity in the upper airways controls early SARS-Cov2 infection in children’. I’m fascinated with the idea of ‘pre-activated’ immunity here. As far as I know vaccines pre-activate immunity to viruses or pathogens by presenting the immune system with a part of that pathogen, or a protein unique to it. But with children, how is their immune system pre-activated? In any case, the article explains that ‘children displayed higher basal expression of relevant pattern recognition receptors [involving interferons] in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-Cov2 infection than in adults’. This finding highlights the importance of interferons and of perhaps trying to maintain their prevalence in older subjects. The article described children presenting in emergency with severe Covid19 as having an impaired IFN response, though the molecular mechanisms for this, and for the protective effects on those children with mild or no symptoms, were unknown.

So the article explains that higher levels of genes coding for RIG-1, MDA5 and LGP2 in the epithelial cells of the upper airways were found in children, but not in adults. RIG-1 is a pattern recognition receptor (PRR) of the innate immune system, responsible for type 1 interferon responses. MDA5 and LGP2 are members of the same family of PRRs. The key being more innate immune cells in that region in children, exhibiting strong antiviral action against SARS-Cov2. This is apparently what is meant by ‘pre-activated’, because these primed cells were already in the upper airways (i.e the nose) of children. However, there appears to be a narrow window of opportunity before viral reproduction, which is especially intense with SARS-Cov2, shuts down this innate immune response. The paradox, it seems here, is that SARS-Cov2’s proteins  can effectively shut down interferon production, but at the same time the virus is highly sensitive to interferon. Anyway, it seems that if we can step up IFN production, assisting the body’s innate immune system, this may enable us to resist the virus (along with vaccination, effective mask wearing and physical distancing of course). One way to do this is by raising the core temperature of the body (inducing hyperthermia). At a core temp of 39 degrees celsius, the amount of IFN released from lymphocytes after mitogen stimulation (i.e inducing mitosis) increases ten-fold from just a degree or so below, at least in vitro. This may sound crazy, but the benefits of induced fever have been proven in various treatments for various infections, including viral infections, in the past, along with other ways of boosting the immune system (vitamin D, zinc and selenium) mentioned previously by Dr Seheult and other experts.

Science science science science science science. Don’t use social media to find out about SARS-Covid19 and its treatment. Never never never never. There are dozens of reputable scientific sites that will inform you, in the USA and in every other country – at least the WEIRD ones. Knowledge is power. Get informed.

References

https://en.wikipedia.org/wiki/Interferon

https://www.webmd.com/drug-medication/interferons-guide#1

Innate Immunity, Interferon, and COVID 19 in Children: Update 128 (video)

https://www.sciencedirect.com/topics/immunology-and-microbiology/myeloid-progenitor-cell

https://en.wikipedia.org/wiki/Mast_cell

https://www.healthline.com/health/basophils

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neutrophil

https://en.wikipedia.org/wiki/Eosinophil

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/monocyte

https://en.wikipedia.org/wiki/RIG-I

https://en.wikipedia.org/wiki/MDA5

https://en.wikipedia.org/wiki/Mitogen

 

Written by stewart henderson

September 6, 2021 at 10:12 pm

Trump: the slo-mo train wreck is far from over – it’s likely to get much worse

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some semi-reluctant future reading – or maybe I’ll just watch the video

This morning I heard an American pundit saying Trump has got to change his approach and become more co-operative with investigating authorities, because his strategy isn’t working. Everybody is offering Trump free advice but he’s unlikely to take it because he’s Trump. People don’t change very much, they certainly don’t become completely different people, certainly not after the age of seventy. Trump has spent his life among crooked rich people, he was brought up by crooked rich people, he only admires crooked rich people, and he will die as crooked as he has lived. That’s his fate.

What pundits should really be working on, IMHO, is limiting his power and curbing his destructive tendencies. Now that the cognoscenti are coming to realise that better vetting processes should have applied to candidates for the overly-powerful position of POTUS, they should be doing their utmost to put obstacles in the way of that power (followed by root and branch reform of the entire political system once Trump is dumped). For example, putting real pressure on White House staffers, many of whom should know by now that the writing’s on the wall, to resign en masse. Or even just to suggest that they do so? Rats tend to desert a sinking ship, but perhaps not if they don’t sense any land in the offing, a safe haven to run to. So maybe it would be the most ethical thing to do, now, to entice Trump’s enablers to abandon him, not entirely without penalty, but with less penalty than if they stick with him to the end. A bit like offering limited immunity. And in the same way, the media should be onto those in Congress who are enabling Trump, or are not being sufficiently vocal in their opposition, or their position in general, to speak their minds more clearly. It’s time for more media hounding, for the sake of the beleaguered nation. Two of Trump’s most vocal supporters in Congress are now being prosecuted as swamp creatures, not surprisingly. More needs to be made of this.

I’m not talking here about ‘weaponising’ the media, or being partisan. This is clearly about corruption and the law. My own early recognition of Trump as a boorish, tasteless, noisome, proudly ignorant, self-serving buffoon had little to do with politics. I’ve learned over this year that he was a ‘lifelong Democrat’ until a few years ago. I didn’t believe it any more than I believe he’s a Republican now. He knows as much about politics, history and international affairs as he does about science. But I’ve also learned more about his inherent dishonesty and crookedness. The responsible media generally recognise this, and they should play, more openly, a heroic role in bringing him down. It wouldn’t be a partisan role, it would be about nation-building, or nation-repairing.

It’s important here not to be partisan, and that’s why it’s essential to focus on the law rather than on politics. Certainly there needs to be a political backlash against Trump, and against his Republican enablers, but I’ve already expressed my skepticism of impeachment, a political process, as a means of dismissing political leaders. All citizens should be subject to the law, regardless of position or profession. This is not to say the mid-term elections aren’t important, as the country needs more liberals and democrats in positions of authority to counter Trump’s fascistic or mafioso-style approach to government. However, the mid-term elections are over two months away, plenty of time for more damage to be done to the country’s political institutions by an increasingly desperate ‘Commander-in Chief’.

The preposterous and disgustingly juvenile, and typically American, idea that their POTUS may be above prosecution simply because he’s too important and vital to the workings of the State, needs to be punctured beyond repair. This seems to me a high-priority issue. Of course, the fact that the USA has given its POTUS too much power will make things difficult in the immediate post-Trump period, but this is a tough lesson that needs to be learned. It seems a constitutional crisis may be just what’s needed to get the nation to wake from its jingoistic slumber and start working on a better, more collegial and distributed power system than the current hero-worshipping laughing-stock it has created for itself.

So let’s go to the issue of indictment, and later we’ll go to the aftermath, which will presumably be a Pence Presidency – not a pleasant prospect, from what I’ve heard.

Unfortunately the indictment of a sitting President is regarded as a constitutional matter – unlike the indictment of any other citizen, presumably. This is a situation that should be rectified. Section 3 of Article 1 of the US Constitution puts it thus:

“Judgment in Cases of Impeachment shall not extend further than to removal from Office, and disqualification to hold and enjoy any Office of honor, Trust,or Profit under the United States; but the Party convicted shall nevertheless be liable and subject to Indictment, Trial, Judgment and Punishment, according to Law.”

Note the unclear wording here. It talks about impeachment first, which to my mind, is irrelevant. It’s the last part that is relevant, though it gets entangled with impeachment – ‘The party convicted shall nevertheless be liable to and subject to indictment’, etc. But impeachment is not about being convicted. The law convicts, surely. The Constitution was signed into law in 1787, and is a source of understandable pride to the American people, but it’s hardly to be expected that it would make everything clear and precise for the next two hundred-odd years. It looks as though indictment should follow impeachment, which is, it seems, misrepresented as ‘convicted’, but it cannot surely be the case that if the President commits what constitutes a ‘high crime or misdemeanour’ (and I really hope that term is clear in US law) he has to be impeached before being charged. That, to me, would be outrageous. It’s very obviously the wrong way round – though of course, you’d have to be sure that the Justice Department had a very sound case before proceeding – perhaps with a speaking indictment (I really like them things). And then, of course, if conviction occurs, impeachment wouldn’t be an issue. It would just be a matter of a change of residence.

It’s astounding, and frankly appalling, that some soi-disant constitutional lawyers really do argue for immunity (while in office) due to the heavy duties of the Presidency  (duties that Trump largely avoids), while other experts argue that Presidents really do have the power to pardon themselves. It’s yet another indication that Yanks, even high-powered legal eagle ones, are in thrall to the wankeries of their worst movies, featuring the vigilante superhero out to save the State from itself, with collateral damage just being part of the thrill.

Considering such jejune but baked-in attitudes about their ‘commander-in chief’, it’s unlikely that Americans will learn much from the current debacle. Still no proper vetting at the outset, still no reduction of pardoning and other powers, still no integration of the Presidency with Congress, still insufficient checks and balances, still the same childishly carnivalesque two-horse races every four years, still the same embarrassing, unreflective jingoism. And still, I find it all quite fascinating. I’m just glad I’m not actually there.

So what will happen by years’ end? Presumably impeachment proceedings, depending on the numbers in both houses – I haven’t yet read up on impeachment, what it requires and entails, and I’ll be doing that soon. But presumably impeachment isn’t easily enforceable, and Trump will ignore it and rely on his base to protect him. That’s when things will get really interesting.

Written by stewart henderson

August 27, 2018 at 1:04 pm

Posted in elections

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