PAID part II - The Toll of TLRs

Upon these receptors, I shall build my church.

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This post ties well with my Paradoxical Acquired Immune Dysfunction hypothesis and all Plagued by Design one, two , The Case for Reverse Mareks, and It´s (viral) Evolution baby I recommend you to read it.

And for the record, the other person who wishes to remain anonymous deserves more of the credit than I.

After weeks of postponing for a while and legitimately not wanting to write this, here we go. Perhaps some will take some value of it and try to fix this mess. After much thought, I decided to this the opposite way we researched. I will start with the upstream, and we go down (hill into a fucking abyss) from there.

First, you need to understand what are Toll Like Receptor. From Wikipedia.

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes.

And this is their function.

This is a simplified and important step on how the mRNA vaccine works.

The Toll-Like Receptor role inside your body is similar to a chemical radar, at the first sign of an invader, it will send signs to your immune system, sound the alarm and recruit an immune response.

You should know both in biology and medicine, that there is no such thing as an on/off button in molecules. The body will always over-compensate, this is quite literally, what a cytokine storm is. An over-compensated immune response feeds itself. Bear this in mind because it is a cornerstone to understanding all this.

In the Revers AIDS hypothesis, I left a breadcrumb. A significant part of this whole mess, while attempting to prove my point that both virus and vaccine cause immune suppression, I left a little hint. It was CVID.

Common Variable Immune Dysfunction, which I first named Reverse AIDS for lack of knowledge. While working our way upstream in pathways, after finding out the mRNA messes with TLRs, trying to find “the answer”, this paper shifted my perspective.

So, for a transient moment the mRNA vaccine design causes immune dysfunction, it shifts your immune response to CD4. I wonder…

Toll-like receptor 7 and 9 defects in common variable immunodeficiency

We demonstrate here that the CVID phenotype includes a selected impairment of responses of TLR7 and TLR9, the predominant TLRs expressed in pDCs and B cells. These defects include loss of cell activation, proliferation, and cytokine production by B cells and pDCs; as a result, CVID B cells forfeit the reinforcement that environmental TLR ligands provide normal human B cells. Our data suggests that the defects in TLR signaling in CVID could play a substantial role in the pathogenesis of this immunodeficiency.

The role of toll-like receptors in B-cell development and immunopathogenesis of common variable immunodeficiency

TLR signaling in B cells plays multiple roles in cell differentiation and activation, class-switch recombination and cytokine and antibody production. Moreover, recent studies have shown functional alteration of TLRs responses in CVID patients including poor cell proliferation, impaired upregulation of co-stimulatory molecules and failure in cytokine and immunoglobulin production. The purpose of the present review is to discuss the role of TLRs in B-cell development and function as well as their role in the immunopathogenesis of CVID.

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency

Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells.

My argument this whole time is the following. In a lot of vaccinated individuals, the mRNA, by modulating your immune response at such a level, turning your TLR in BILLIONS of cells, is inducing a transit (momentarily) CVID state, immune dysfunction for a few weeks to months. And the body will overcompensate the immune response.

TLR have been of major therapeutic interest.

Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics

However, excessive TLR activation disrupts the immune homeostasis by sustained pro-inflammatory cytokines and chemokines production and consequently contributes to the development of many inflammatory and autoimmune diseases, such as systemic lupus erythematosus (SLE), infection-associated sepsis, atherosclerosis, and asthma.

The expression of TLRs can be found in a variety of immune cells (e.g., dendritic cells, monocytes, macrophages, and B lymphocytes) and non-immune cells (e.g., epithelial cells, endothelial cells, and fibroblasts;)

The entire paper above is a valuable resources and should be read for those who want to understand the scope of this

A change in the signaling of TLR alone can change the outcome of many diseases.

Merely conjecture… right ?

The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses

Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

Interestingly, we observed important heterologous effects of BNT162b2 vaccination on IFN-γ production induced by other stimuli as well (Figures S2E, 2F). BNT162b2 vaccination decreased IFN-γ production upon stimulation with the TLR7/8 agonist R848

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8

The same sequences induced human DC activation in terms of phenotype and functions, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.

There are multiple mechanisms for the mRNA to induce (setting off) and feed cancer, but we must start at the beginning.

The Role of TLRs in Anti-cancer Immunity and Tumor Rejection

R848-stimulation of TLR7/8 overexpressing pancreatic cancer cell line resulted in increased cell proliferation and reduced chemosensitivity (17). The authors also show increased nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and cyclooxygenase-2 (COX-2) expression upon TLR7/8 stimulation that has been previously linked to immune evasion and immunotherapy resistance (65).

Therefore, it seems that TLR signaling can act as a double-edged sword in cancer (summarized in Figure 1), with its pro- and anti-cancer roles that have been also reviewed by others

As a final note, a reminder that the mRNA vaccine literally kills your NK cells response for a while…

To the layman, the mRNA vaccine “overwrites” important parts of your biological response against most diseases and foreign pathogens, and changes your “alarm” signs, making them go off/on at disproportional levels and messing if your immune system. It makes you susceptible to reinfection and getting sicker when infected by normal infections.

For everyone else. Most countries in the world experienced an abnormally strong flu season. You can also search for sepsis, and you get lots of doctor accounts in social media telling about the sudden increase of septic patients that didn’t even know they were septic.

Jonathan Irons @worldedge_group

The mysterious case of the abnormally strong flu season. And a few extra breadcrumbs for all.

If you think this is hard to take, you should stop here, because the next one it gets exponentially worse, it literally gave me and the other person mild depression for a couple of weeks.

And another blast, from the past. Or a message for future generations.

Jonathan Irons @worldedge_group

@KathMLee1 I spend close to 18 months saying the spike centric jab would be a mistake mankind will bitter for decades. I will spend the next 18 saying "Turns out turning off Toll Like Receptors had consequences" lol