[conspire] Numbers racket

[Deirdre Saoirse Moen]

On Mon, Apr 27, 2020, at 4:45 PM, Ruben Safir wrote:
> On Mon, Apr 27, 2020 at 03:11:53PM -0700, Deirdre Saoirse Moen wrote:
> > On Mon, Apr 27, 2020, at 2:08 PM, Ruben Safir wrote:
> > > On 4/27/20 5:55 AM, Deirdre Saoirse Moen wrote:
> > > > Exactly, and that assumes that there’s immunity, which we still do not
> > > > know.
> > > 
> > > When there is no immunity the patients die.  That is what happens with
> > > HIV.  There is no immunity and the patients never overcome the disease
> > > and they die.  Most patients take this one and never get more than a
> > > cold.  That is the defintion of immunity.
> > 
> > It is not, not at all. We do not know they cannot get *reinfected*. That is an assumption that people have been making that is unwarranted.
> 
> It is.  That is what the anti-bodies are, and how the B and T cells
> interact.  The reason it fails for HIV is that HIV attacks the T-Cells.

I know how HIV works, actually, it is kind of a cool hack. Specifically, HIV uses CD4 to gain entry into T-cells specifically, so it uses the immune system against itself. Real evil genius territory.

It then uses those CD4 cells, which normally activate the longer-term parts of the immune system to generate B- and T-cell responses as little virus factories. The NY Times link below is pretty good at explaining the general sorts of ways viruses hijack the existing cell processes, though HIV's specifics are different from COVID's. And, of course, what's being hit is that you aren't fighting an infection you were supposed to be, which is why your body made that CD4 cell in the first place. Then it starts making CD8 (killer) cells to try to kill the CD4 cells that have gone rogue. (Normally the CD8 is part of the usual cell teardown as apoptosis is actually quite a complex process to specifically prevent everything going everywhere.)

I know a lot more about HIV, including reverse transcription, how reverse transcriptase works, yada yada, but let's not go there. And, specifically, because of the errors in reverse transcription (which is true for all retroviruses), they are particularly difficult to fight well without serious consequences long-term because the mofos mutate.

One advantage, we hope, in the COVID-19 deal, is that there's a specific error-correcting protein in the COVID bundle (NSP14):

https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html

> > 1. We don't know that  we can create an effective vaccine because we have never created an effective vaccine for the betacoronavirus family for humans.
> 
> The problem with the vaccine ... actually there are a lot of problems
> with the vaccine, most of them political.  It is likely we can create a
> vaccine.. it is very very likely.

We may not be able to create an actually viable vaccine that will continue to keep the disease at bay. THAT was my point. It is unproven in the betacoronavirus family in humans.

> > 2. Even if we did, we don't know that it would actually prevent reinfection, or that reinfection wouldn't actually be worse (my point in raising dengue).
> 
> There is no way you are getting reinfection.  Your completely
> misunderstanding this.  When your body can't produce immunity, you NEVER
> defeat the virus.  You remain sick forever until you die.

You are thinking I do not understand what I understand. I have had graduate level work in immunology specifically on blood and how it generates antigens and how to keep it from doing so. I've worked on FDA-approved projects to schedule injections. Now, you want to tell me I don't understand how hearts work, you're probably right on that, but blood I understood pretty well even before I started that project, which is why I was hired.

This is the stuff I worked on scheduling injections for: https://en.wikipedia.org/wiki/Rho(D)_immune_globulin

> The immunity can wear off in time, but that is true of most viruses.

I get the differences between IgM (which I call IgMmediate) and IgG (and IgE for true allergies, etc.) and B and T cell mediated immunity (etc). Do I know everything? No. But I did actually turn down postdoc offers because I didn't want to go a doctorate route.

> > I'm going to harp on the second because it's more fun.
> > 
> > The cytokine release storm that causes the unreal lung issues 
> 
> This has nothing to do with cytokines.
> 
> By the time you get to a cytokine storm, the game is over.

And it may be.

> It might be difficult to develop a vaccination, but it is really just a
> matter of time.  Immunity, there is no doubt about it.  We build
> immunity to these viruses all the time.  The alternative is exctinction.

READ. UP. ON. DENGUE. That way you'll understand my point.

I absolutely hope the dengue exception doesn't apply, truly I do. But we take immunity for granted, and this is a case where we shouldn't.

> > https://en.wikipedia.org/wiki/Antibody-dependent_enhancement
> > 
> 
> Umm - I have other sources.  Goodman and Gilman amoung others
> https://medicostimes.com/goodman-gilmans-pharmacology-pdf/

Janeway's Immunobiology is the usual text for people going into the field (as opposed to related fields like pharmacy). It's what I had, though god knows where my copy ran off to. Just as well as cells were still using pickaxes for signaling back then. ;)

Sompayrac's How the Immune System Works is currently recommended for studying for boards and is very intro friendly (for those others reading along).

Deirdre