Mastodawn

Jeff Gilchrist Jan 6, 2023

How #COVID actively suppresses and evades your #immune system [Part 1]

This thread highlights multiple methods that the virus uses to help keep #reinfecting people including #MHC-I and #interferon #suppression, #evasion of Natural Killer (NK) cells, and reprogramming of #monocytes. 🧵 1/

The one page web view is available here: https://pingthread.com/thread/1611333222419566594

Thread by jeffgilchrist: How #COVID actively suppresses and evades your imm... - PingThread

How #COVID actively suppresses and evades your immune system [Part 1] This thread highlights multiple methods that the virus uses to help keep reinfecting people including MHC-I and interferon suppression, evasion of Natural Killer (NK) cells, and reprogramming of monocytes.🧵1/

PingThread

Jeff Gilchrist Jan 6, 2023

COVID has been doing this to varying degrees since the beginning which further reinforces that a vaccine only policy is not enough to stop the cycle of sickness, long term disability, and death. Some people have the privilege of clean drinking water so they do not have to boil their own water for it to be safe because the infrastructure was put in place to clean the water. 2/

Jeff Gilchrist Jan 6, 2023

We need similar changes in infrastructure now to provide clean indoor air for people, not just from pathogens but from other pollutants as well ( https://mstdn.science/@jeffgilchrist/109580638330581137 ). 3/

Jeff Gilchrist (@[email protected])

Attached: 1 image The importance of indoor air quality #IAQ This thread looks at the impact of #cleaning indoor #air, not just from pathogens in #aerosol #particles but also from other air #pollutants linked to various health problems, and what we can do about it. #IndoorAirQuality #Ventilation #CO2 #PM25 An unrolled one-page web view for this long thread that may be easier to read or share can be found here ( https://pingthread.com/thread/1607379781892575234 ). 🧵 1/

mstdn.science

Jeff Gilchrist Jan 6, 2023

First some simplified background info, CD8+ T-cells and Natural Killer (NK) cells are both immune system cells with similar goals to kill (cytotoxic) infected and transformed cells but their recognitions and memory mechanisms are very different ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880541/ ). 4/

CD8+ T Cells and NK Cells: Parallel and Complementary Soldiers of Immunotherapy

CD8[+] T cells and NK cells are both cytotoxic effector cells of the immune system, but the recognition, specificity, sensitivity, and memory mechanisms are drastically different. While many of these topics have been extensively studied in CD8[+] T ...

PubMed Central (PMC)

Jeff Gilchrist Jan 6, 2023

Cells express MHC-I molecules on their surface as a surface recognition element to signal the cell's physiological state to immune cells such as T-cells and NK cells ( https://pubmed.ncbi.nlm.nih.gov/11256571/ ). When a cell is infected for example, it will present parts of the virus (antigen) on the surface using MHC-I as a way to alert the immune system for help. 5/

MHC class I molecules, structure and function - PubMed

MHC class I molecules (MHC-I) are cell surface recognition elements expressed on virtually all somatic cells. These molecules sample peptides generated within the cell and signal the cell's physiological state to effector cells of the immune system, both T lymphocytes and natural killer (NK) cells. …

PubMed

Jeff Gilchrist Jan 6, 2023

The T-cells look for specific antigens they have been "trained" to find and will bind to a cell that matches and then activate their response such as killing the cell.

With NK cells however, there is no single dominant receptor for NK cell recognition but they express an array of innate activating and inhibitory receptors to sense their environment and respond to alterations caused by infections, stress, and transformation. 6/

Jeff Gilchrist Jan 6, 2023

Innate immunity cells are the first responders to sites of infection and NK cells are much quicker to establish a robust response than CD8+ T-cells ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880541/). NK cells also have the ability to recruit T-cells and other adaptive responders to the sites of infection. 7/

CD8+ T Cells and NK Cells: Parallel and Complementary Soldiers of Immunotherapy

CD8[+] T cells and NK cells are both cytotoxic effector cells of the immune system, but the recognition, specificity, sensitivity, and memory mechanisms are drastically different. While many of these topics have been extensively studied in CD8[+] T ...

PubMed Central (PMC)

Jeff Gilchrist Jan 6, 2023

You can learn more watching this @[email protected] "Immunology 101 for non-immunologists video" ( https://www.youtube.com/watch?v=jeN8v5I5VNA ) and @[email protected] "How your immune system actually works video" ( https://www.youtube.com/watch?v=lXfEK8G8CUI ). 8/

COVID-19 Immunology 101 for Non-immunologists by Akiko Iwasaki, Ph.D.

YouTube

Jeff Gilchrist Jan 6, 2023

Now that you have a little background, how does the COVID virus try to avoid the immune system? The newer Omicron variants exhibit an even greater ability to suppress surface MHC-I expression in cells the virus infects ( https://www.biorxiv.org/content/10.1101/2022.05.04.490614v3.full ). H/T: @VirusesImmunity 9/

Jeff Gilchrist Jan 6, 2023

That means CD8+ T-cells can't as easily "dock" with the infected cell and kill it. The study found multiple variants BA.1, BA.2.12.1, BA.4, and XAF all had significantly higher MHC-I suppression than the original WA1 strain but had no impact in MHC-I on the surrounding cells.

This allows infected cells to be more "invisible" to CD8+ T-cells that otherwise would have been able to find and destroy the cell which lets the virus continue to replicate. 10/

Jeff Gilchrist Jan 6, 2023

Another study found that COVID virus also suppresses the danger signals that are supposed to help NK immune cells recognize (with their NKG2D receptor) and kill infected cells ( https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01791-0 ). H/T: @[email protected] 11/

Jeff Gilchrist Jan 6, 2023

COVID virus causes NK cells to exhibit poor cytotoxic (killing) responses to infected cells and instead preferentially target and kill uninfected bystander cells. The researchers found that NK cells are actually really good at killing COVID infected cells before the virus has had a chance to replicate and suppress NKG2D-L compared to 48 hours after infection ( https://twitter.com/m_janelee/status/1607791318230523906 ). 12/

Maddie Lee on Twitter

“Actually, if you pit NK cells against infected cells before the virus has had a chance to replicate and suppress NKG2D-L, the NK cells are great at killing infected cells! Later on, once NKG2D-L is suppressed? Not so much. 4/10”

Twitter

Jeff Gilchrist Jan 6, 2023

The part of the virus that suppresses NKG2D-L to prevent NK cells from killing the cells they infect is Non-Structural Protein 1 (Nsp1). The researchers found that just putting Nsp1 inside the cell without any other part of the virus was enough to both suppress NKG2D-L and stop NK cells from killing it. When they tried using various other components of the virus instead, the NK cells kept killing the cells, with most increasing the chance of the cell being killed. 13/

Jeff Gilchrist Jan 6, 2023

This is yet another way for COVID to get around the immune system with methods to make infected cells more "invisible" to both immune CD8+ T-cells and NK cells. The researchers point out that the Nsp1 protein in the virus is highly conserved and needed for viral replication so it may make a good target for therapeutics against other families of coronaviruses as well. 14/

Jeff Gilchrist Jan 6, 2023

It is interesting to note that due to genetic variation about 4% of a population studied lacked the NKG2C receptor on NK cells and 30% have the receptor only partially available which had a significant impact on the development of severe COVID infections ( https://www.gimjournal.org/article/S1098-3600(21)01448-9/fulltext ). H/T: @0bj3ctivity 15/

Jeff Gilchrist Jan 6, 2023

The study found people without the NK receptor or having a partial receptor were significantly overrepresented in hospitalized patients, particularly in patients requiring intensive care compared to those with mild symptoms. 16/

Jeff Gilchrist Jan 6, 2023

These multiple methods of immune suppression and evasion by COVID help explain why viral loads can get high enough again in people that are previously infected and/or vaccinated to become contagious and transmit the virus to others before the body can get the infection under control. 17/

Jeff Gilchrist Jan 6, 2023

For people who are vaccinated or previously infected, even though your immune system has seen a COVID variant before and you already have T-cells that can recognize the virus the new variant you are exposed to can suppress the mechanism that those T-cells (and NK cells) use to identify and kill COVID infected cells giving the virus time to replicate a lot before other parts of the immune system notice and start fighting off the virus. 18/

Jeff Gilchrist Jan 6, 2023

That is why people can't "vax and relax" forgoing all other precautions because exposure again can still give the new virus infection a chance to replicate enough to cause trouble in your own body and also potentially infect other people too. 19/

Jeff Gilchrist Jan 6, 2023

Part 2 will look at how the COVID virus reprograms innate immune functions such as white blood cells (monocytes) that increase the risk of blood clots and suppresses innate immunity to other viruses and bacteria increasing risk of secondary infections. 20/

Jeff Gilchrist Jan 7, 2023

Some people are asking, why does this immune suppression happen to people who have been vaccinated and never infected before as well as people who have been infected already? 21/

Jeff Gilchrist Jan 7, 2023

It is happening to all people because the mechanism to evade and suppress the immune system that I describe in this thread is the ability of the virus itself to turn off/reduce the ability of CD8+ T-Cells and NK immune cells from detecting the cells it has infected, allowing the virus to fly under the radar, vaccinated or not. 22/

Jeff Gilchrist Jan 7, 2023

If you get infected, among many other things, your body develops T-cells that recognize the virus Spike protein. When you get vaccinated, you also develop T-cells but without getting attacked by a functional virus. 23/

Jeff Gilchrist Jan 7, 2023

When you get infected again (or first time after vaccination) those T-Cells are trying to specifically hunt down and kill COVID infected cells it already learned about but they can't easily find them and kill them because the new virus infection is blocking the ability for the T-cell to do that. So this happens in both scenarios. 24/

Jacqueline Jannotta Jan 7, 2023

@jeffgilchrist So is does this essentially mean we each get one "bye" -- either vaccination or original infection (with vaccination obviously being the preferred choice!)? And after that all bets are off -- or damage definitely done and T-Cells can't do their job? Just trying to look at this horror in the face and understand clearly. Thx for sharing your insights!

Jeff Gilchrist Jan 7, 2023

@JacquelineJannotta not sure I understand what you think is going on. The virus has the ability to hide from certain types of immune cells (CD8+ T-cells and NK cells) so every time you get exposed to COVID it can keep hiding even if your immune system has seen it before. Other parts of the immune system kick in and eventually fight off the virus in most people which is why vaccinated have less severe disease/death, but it takes longer to clear with the hiding.

@jeffgilchrist
I've seen no evidence that all SARS-CoV-2 reservoirs are fully remediated upon symptom cessation. And studies documenting viral persistence long after clinical recovery are in the high dozens by now. We most likely carry some form of this disease for life. Pretty depressing.
@JacquelineJannotta

Jacqueline Jannotta Jan 17, 2023

@noyes @jeffgilchrist Putting it out there that the science/medical community can up-level their game in short order so we all understand this better, and above all manage it well. Because, as I'm sure we agree, the current behavior of denial isn't serving us.

J.H.Noyes Jan 17, 2023

@JacquelineJannotta
MGMT would rather we did not understand Covid. Think about all the fantastic claims regarding CD8 response that were made even though the deep impairment inflicted by ORF8 was on record by 03/20.

Everyone at NIAID, NIH, and the CDC must have been aware that CTL function was compromised, yet immunofabulist narratives flourished and were used by ExBr to justify eschewing NPIs for the disastrous Pax, Vax, and relax policy that has killed or maimed millions.
@jeffgilchrist