The one tool in the toolkit that SARS2 can’t dodge

It will be something to watch a ORF7a:A13V, ORF9b:I5T, ORF9b:N55S trifecta in action. Thus effectively muting both innate and adaptive immunity. Orf7 to suppress MHC-I and then Orf9b mutes to suppress IRF3 and in turn type 1-IFN. Won't be pretty.

— Michael (@mrmickme) March 17, 2023

I wish to provide some explanation here. The concern expressed here is justified, but these people don’t draw the natural conclusion: Provoking adaptive immunity through vaccination was a poor strategy. The novel Indian variant is now already rapidly changing itself further as it shows up in highly vaccinated nations, further increasing its already massive growth advantage.

People have noticed hospitalizations are rapidly increasing wherever the XBB.1.16 variant shows up. This is not surprising, it’s a logical consequence of improved Interferon suppression. The ongoing improvement in Interferon suppression is not shocking either: This thing is descended from bat coronaviruses. Bats tolerate these viruses because bats have a very good Interferon system that keeps them in check, so you would expect this virus to have the intrinsic capacity to evolve towards strong Interferon suppression.

Let me give a brief overview of what some of the functions of the immune response induced by the vaccines look like and how they’re doing by now:

-Neutralizing antibodies. These are very effective when they work, but they’re now utterly gone against the XBB’s.

-Antibody dependent cellular cytotoxicity. Should still be there, unless the IgG’s have shifted towards IgG2 and IgG4, which they have against Spike in people vaccinated with mRNA before natural exposure.

-CD8+ killer T cells against Spike. Should still be functional, but wide disagreement exists over the degree of importance. Infections may also lead to CD8+ killer T cells activity against other proteins.

-NK cell activity against Spike. Should also still be functional.

But now here’s the issue. With the mutations mentioned in the Twitter post, you would see downregulation of the MHC-I molecule. This is the molecule infected cells use to show to your immune system that they’re producing harmful protein material, in this case the new SARS2 virus.

As this virus evolves, it gets better at shutting down this MHC-I molecule, so the NK cells and the CD8+ killer T cells that learned to look for viral proteins displayed inside this molecule become useless. In this case, you’d be left with a situation where most of the adaptive immune response becomes pretty useless.

On the other hand however, NK cells also have other tactics they’re able to use. One of these, a relatively well studied one, is to look for cells that fail to display the MHC-I molecule. Such a thing is suspicious and although it is tolerated under some conditions, under other conditions it can cause an NK cell to kill the cell. You would expect this mechanism to continue functioning when the virus evolves to get much better at downregulating the MHC-I molecule.

But more importantly, the NK cells have another mechanism through which they look for infected cells: They have receptors that look for pathogen associated molecular patterns: Stuff they see that suggests a cell is producing pathogen associated material. In addition to this there are also danger associated molecular patterns (DAMP): Stuff that cells produce when they’re not doing well (like when a virus infected them), like heat shock proteins.

Such stuff triggers inflammation, attracting more immune cells that will try to figure out what’s going on and address the problem. And then there’s SAMP: Self Associated Molecular Patterns, stuff that encourages the innate immune system to relax. You have to ask yourself: If we fool a cell through vaccination into expressing mRNA with some synthetic nucleotides that prohibit the cell from recognizing what’s going on, will it produce the sort of damage associated molecular patterns (DAMP) that encourage the NK cells to go ahead and pull the trigger? Probably not, you just get the adaptive immune response. Remember, these mRNA vaccines are not normal vaccines, they stealthily trick your cells into producing alien genetic material.

But most importantly, the Natural Killer cells have a Natural Cytotoxicity Triggering Receptor. It looks for the sort of stuff infected cells produce when infected by a virus. Viruses have to make use of certain molecular structures to allow them to enter other infected cells, so many of them tend to have some broad similarities, which the Natural Cytoxicity Trigger Receptors are able to look for. Examples of the receptor include NKp46, NKp44, and NKp30. Importantly: These patterns that the Natural Cytoxicity Trigger Receptors look for do not depend on the MHC-I molecule, as this stuff is displayed independently of this molecule.

Whenever the Natural Killer Cells get to do their job against a virus, it encourages them to proliferate. HOWEVER, IF THE NATURAL KILLER CELLS ARE BEATEN TO THE RACE BY ANTIBODIES, THAT MEANS THEY DON’T GET TO PROLIFERATE THEMSELVES!

Have a good look at this:

Influenza A Virus HA Interaction with NKp44 and NKp30

Building upon this initial study, Arnon et al. demonstrated that IAV and SeV infected cells, in addition to SeV HN transfected cells, interact with hNKp44-Ig, but not hNKp30-Ig [39]. This interaction was also abrogated by anti-HA (IAV) or anti-HN (SeV) antibody blockade, or pretreatment with purified HA (IAV). Anti-NA antibody blockade increased IAV interactions with NCRs [39], confirming results previously reported by Mandelboim et al. [28]. IAV-infected cells more readily engage with hNKp44-Ig than hNKp46-Ig [29]. This observation aligns with the predicted glycostatus of the NCRs–hNKp44 is more heavily glycosylated than hNKp46 and is likely to have increased binding opportunities simply due to number of glycosites present.

I looked up the study here and I excerpted their findings below:

So I’m going to explain this in simple English:

The Natural Killer Cells are very good at killing infected cells, by looking for certain patterns that all viruses in certain families need to have to be able to survive as viruses.

The Natural Killer Cells get to expand their population when they get to do their job, of finding and destroying infected cells that display these patterns.

The Natural Killer Cells can’t recognize these patterns when antibodies are attached to those molecules.

Because they can’t recognize these patterns, that means that infections that are immediately dealt with by antibodies and trigger antibody dependent cellular cytotoxicity can’t help the Natural Killer Cells looking for the pathogen associated molecular patterns expand themselves.

This means that once the antibodies can no longer do their job (IE now that the neutralizing antibodies are gone against XBB and people have lost IgG3 after breakthrough infections), the Natural Killer Cells have not had the opportunity to fill in the gap by expanding themselves.

And we have to keep in mind: The virus exhausts and depletes the Natural Killer cells. So you want people to have a big army of Natural Killer cells that survived previous infections and proliferated themselves. When faced with a small and mismatched army, the enemy overruns us.

Keep in mind that Natural Killer cells also do other important stuff: They talk with other immune cells through signaling molecules, which helps attract those cells which all have their own ways of helping to deal with an infection, some of which involve killing an infected cell, some of which simply involve cleaning up viral particular circulating outside the cell and in the extracellular matrix.

None of what I’m explaining here is very revolutionary groundbreaking information, I simply followed Geert van den Bossche’s lead in looking at how the NK cells behave and wanted to give you a look at some of the information available in the literature.

The NK cells as part of the innate immune response are elegant, they look for general patterns that many different kinds of pathogens are forced to use to infect us. It’s only when the innate immune response can’t solve the problem on their own, that the more brute force methods of the adaptive immune response become involved.

In places like India and especially Africa, people’s NK cells have received training from infection before vaccination. The unvaccinated in Western nations have generally been exposed many times by now, so their NK cells have received training and expanded in the sort of tissues SARS2 tends to infect.

But now consider this: You were vaccinated multiple times and whenever you got a breakthrough infection, CD8+ T cells looked for peptides in the MHC-I molecule and antibodies bound to the infected cells which stimulated antibody dependent cellular cytotoxicity.

One day the new and improved SARS2 from India arrives, which now completely evades your neutralizing antibodies, has become much better at stopping cells from displaying its material in their MHC-I molecule and also gotten much better at suppressing Interferon. And your IgG2 and IgG4 antibodies fail to trigger antibody dependent cellular cytotoxicity from your NK cells and CD8+ T cells.

Maybe with all the other branches of immunity struggling to deal with this infection your NK cells will finally get an opportunity to expand themselves, but the NK cells will need time to expand themselves. And until they expand themselves, that puts your body at a big disadvantage.

In contrast, if you have had natural infections that led to the NK cells expanding themselves and taking up residence in the sort of tissues where this virus tends to show up, your body is well prepared for these more virulent variants that got much better at suppressing both the innate and the adaptive immune response.

I have argued many times that I don’t think it’s a good idea to avoid infection: You want the body to have the opportunity to learn over time how to deal with a virus that is gradually getting better at dodging our immune response. And so I really hope that most of you have been infected a few times by now, so that the body has had an opportunity to expand the sort of immune response that is variant independent, as well as having had the opportunity to remodel tissues that are readily affected by this virus, to make them more resilient.

I am very sorry that people were fooled or pressured into taking these vaccines, but I am convinced this happened for a metaphysical reason. Regardless of whether you have been vaccinated or not, I hope that you have been merciful towards nature, so that you can count on nature’s mercy towards you. Plants have a natural talent to help human beings cope with infection by viruses of this nature, plant terpenes for example have synergistic antiviral effects.