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Author Topic: Breakthru Diagram shows CD8 LTNP info presented New most advanced  (Read 3658 times)

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Offline bimazek

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Breakthru Diagram shows CD8 LTNP info presented New most advanced
Diagram shows CD8 LTNP breakthru info presented New most advanced

http://bloodjournal.hematologylibrary.org/content/vol109/issue11/images/large/zh80110704370001.jpeg

the reason why i think this is the most breakthru diagram will be detailed below, what i will try to do here is explain what the diagram means in simple terms so anyone can understand...
this diagram shows the different ways that a CD8 hiv specific killer cell can live and be created, they are created by interaction with APC -antigen presenting cells that is the top of the diagram

the left column which ends with a CD8 cell filled with green clover symbols is good news it is a LTNP, or someone who has hiv but is not getting sick from it the body and the cd8 cells are suppressing and sopping up enough of the virus that thing are not going too bad, this is for people over say 350 or 400 or 200 even

the right column which ends with a CD8 cell filled with spots and having the PD-1 attached is bad news, that is when the infection causes the pd-1 receptor to be high and this pd-1 tells the cd8 cell to turn off and stop functioning

both columns are happening in each hiv person simultaneously

also these processes are happening  billions of times a second, i am guessing at the number

now also important is that it is the number of pd-1 on the surface of the cd8 cell, they only show one pd-1 for simplicity but there are thousands or millions of pd-1 on each cell, when say 75% get to the high state, then the cd8 stops working and the person gets rapid progression of dying of cd4 cells
i repeat
then the cd8 stops working and the person gets rapid progression of dying of cd4 cells
cd4 cells
cd4 cells
drop

now both these processes happen simultaneously and probably even in LTNP

but the LTNP are mostly in the clover

also if you are on haart you are mostly or 99.9% in the clover side (the tests on the % at different cd4 levels has not been done as far as i know)

all cats and some monkeys and hyeinas and such who have thier own species hiv
their body keeps them forever in the green clover side

notice how complex this process to make the clover green Tcells, but also remember that all the LTNP have this same process and all stay in the and with the clover green Tcells

 
Basically,  all LTNP longterm nonprogrssrs have a common reason why they are LTNP and that was shown by Chinese who prove that all  LTNP have something in common and that there can be new therapeutic options.
 
the reason it is newsworthy is who would have thought that all LTNP longterm nonprogrssrs would have exactly the same thing going on internally, even i thought that it would be found to be multiple reasons...  as the second article and the link with the complicated chart, which is still in first version because the science is just understanding it...
 
this diagram alone is a revolution in our understanding of hiv... this diagram shows why some have low cd4s and no symptoms and others with same 50 cd4s are very sick, it tells why things can improve for a time, why certain vitamins and substances and nutrients can help but not elimentate hiv, the complexity of the pd-1 and cd8 cell and remembering that all animals who do not progress to disease have these same type of cd8 cells with out pd-1 exhaustion...


some of this is my opinion and may need to be completely proven and fleshed out...
this diagram shows how and why someone can be very sick with very high cd4 cell counts above 300 or even 400, also shows why people get diseases when on haart ... for example my friend at being alive in LA is on haart and doing great cd4 well over 500 and he got shingles, and i am not on meds never have been and i got shingles (why because as you see the APCs-cd8-pd-1process is constantly in a battle to supress and subdue virus on or off haart)
this is why many get many hiv related illnesses (not metabolic illnesses or toxic effects) which on haart or before or immediately after going on a drug holiday
think about it get your md consultants to explain this chart and how it would work for someone 2 years after infect, 5 years, 11 years, on haart after haart, during treatment interupt, and also... this explains why so many have such different experiences when they seroconvert, for example some almost die at conversion others feel almost nothing... it is because of the APCs-cd8-pd-1process
http://bloodjournal.hematologylibrary.org/content/vol109/issue11/images/large/zh80110704370001.jpeg
Antigen-presenting cells (APCs)
 
it is late and i am writing fast my thoughts and insights,

 i hope you can give some time to this critical discovery if you know about the immune system and you can post more info...
why does a cat with feline FIV not get disease -- APCs-cd8-pd-1process
why does a gorilla with SIV not get disease -- APCs-cd8-pd-1process
why does someone spike up rapidly after stopping haart sometimes -- APCs-cd8-pd-1process

http://bloodjournal.hematologylibrary.org/cgi/content/full/109/11/4593
 
why do i think this is so important, because it give clues and hints and areas to study about why the process and numbers of cd4 cells does not tell everything about how sick a person is and such

this is an incredibly complex process, each step requires hundreds of thousands of partial differential eq. to be solved simultaneously which is easy for the body because the shapes of the molecules cause the bindings and couplings


if you understand the immune system please post about

what is difference between

Tn
Tp
Te
Tm

cells

i think these are all cd8 Tcells and the
e=effector
m=mature
p=proliferative (producing lots of copies)
n=maybe innate or natural

ok... i found out the definition of these...

   Tn/Tp/Te/Tm cells: naive/primed/effector/memory T cells.

Also this is very very interesting.... "The inhibitory receptor PD-1 is rapidly up-regulated on activated T cells. Its expression is decreased on effector T cells and diminished on memory T cells after antigen clearance. Upon antigen restimulation, effector T cells also up-regulate expression of PD-1. Therefore, sustained stimulation of naive and/or effector T cells during chronic virus infection will lead to accumulation of PD-1+ T cells. Antigen-presenting cells (APCs) in HIV-1–infected patients express high levels of PD-L1 or B7-H1.6 It is likely that impaired APCs with PD-L1 may help sustain PD-1 expression on T cells and impair their effector maturation, and allow chronic viral infection (see figure). "


impaired APCs with PD-L1 may help sustain PD-1 expression on T cells and impair their effector maturation, and allow chronic viral infection --this means that it may be the APCs that cause the CD8s to become disfunctional and simply somehow finding a treatment of the hiv specific upregulated APC cells that have pd-1 will be a great treatment.

http://en.wikipedia.org/wiki/Antigen-presenting_cell




also remember that this shows one line step by step but in reality each step produces a thousand or ten thousand copies of itself so it is really a tree structure and the end product is billions of working or disfunctional cd8 tcells

also the question on the side

chronic virus / Ag   &  pd-L1  sustains pd-1 expression?

what is the Ag?

it seems the science is searching for what drives this process forward

why is cd29 yellow or white

what is TCR?

notice on bottom far right the pd-1 is high or expressing that is a disfunctional, not working exhausted CD8 cell

the question is how to push things over to left side

notice the top right

APC Virus +/-    it seems to me they do not even know if it is virus activated antigen presenting cells that are driving the distruction and  disfunction, not working exhausted CD8 cells into existance

remember this is a first diagram only a few weeks after the discoveries and so science is trying to grip and grab the complex idea into a simple form

thus the diagram is simple

think of this... some one might be at 100 cd4 cells but the process of the green clover and the left and right column is in balance so they remain stable, where another person where the green clover cd8 cells are going fast is sick because they loose cd4s faster

also they do not know what influences these processes

anyone who can post please do if you know about immune system

thanks
« Last Edit: June 12, 2007, 12:57:59 PM by bimazek »

Offline bimazek

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Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #1 on: June 12, 2007, 01:08:25 PM »
after further reading and study... http://en.wikipedia.org/wiki/Antigen-presenting_cell
here is what i want to say... because...
The professional APCs are very efficient at internalizing antigen, and then displaying a fragment of the antigen, bound to a class II MHC molecule, on their membrane. The cd8 T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen presenting cell. An additional co-stimulatory signal is then produced by the antigen presenting cell, leading to activation of the T cell.

great this works fine for all infections of the body and all viral infections, it is only hiv BECAUSE it is hiding in one of the immune system cells itself that gets this very effiecient process confused

the signals do not know when to turn the cd8 t cells on and off because over a period of years all the immune cells get overwhelmed with and signaled and basically the green clover type cd8s dont get produced enough
basically the process gets messed up

http://en.wikipedia.org/wiki/Chemotaxis  ... here it talks about how the immune cells after it captures and eats hiv it kind of crawls back to the lymph node, and if you have hiv you may have experienced this swelling and pain and accumulation of the soldiers of the immune system as they head to the nodes















These professional APCs are very efficient at internalizing antigen, either by phagocytosis or by endocytosis, and then display a fragment of the antigen, bound to a class II MHC molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen presenting cell. An additional co-stimulatory signal is then produced by the antigen presenting cell, leading to activation of the T cell.  There are three main types of professional antigen-presenting cells:
    * Dendritic cells. Dendritic cells have the broadest range of antigen presentation, and are probably the most important APC. Activated DCs are especially potent TH cell activators because, as part of their composition, they express co-stimulatory molecules such as B7.
    * Macrophages
    * B-cells. B cells, which express antibody, can very efficiently present the antigen to which their antibody is directed, but are inefficient APC for most other antigens.

Offline powerpuff

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  • Posts: 138
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #2 on: June 12, 2007, 01:55:09 PM »
hi, i'm new, bare with me. ??? how des this help in treatment? shows advancement of disease progression understood will this help in treatment options?

Offline powerpuff

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Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #3 on: June 13, 2007, 03:01:25 PM »
my question is shuting down the pd1 expression doesn't that cause autoimunne disfunction???
isn't that dangerous or  not??/? ??? i might be totally wrong  any insight to my theory??? i thought i read it somewhere?

Offline powerpuff

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  • Posts: 138
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #4 on: June 13, 2007, 03:10:56 PM »
would this be a new angle of treatment( meds) or the body able to fight off infection/// in lay terms
anyone doing trials.. ::)

Offline bimazek

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  • Posts: 781
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #5 on: June 13, 2007, 03:21:02 PM »
Yes there is a trial for anti pd-1 monoclonal antibody being given to humans for melanoma, that is first use, then they are looking at trying to find a molecule or med that will do the same thing

do a search on my user name and

bimazek

and

pd-1

or cd8


Offline bimazek

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  • Posts: 781
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #6 on: June 16, 2007, 12:54:45 AM »

can one of the smart bio tech med type guys on here explain this diagram, or think about what could be causing this receptor to be turned on... is it a protein or a hiv protein

nef

tat

we know that without nef there is no disease progression



http://forums.poz.com/index.php?topic=13135.0

also this oxford study says that  IL-4 produced dramatic reduction in PD-1 expression and is not always thought of as a ‘danger’ signal, although it shares important ‘danger’ characteristics (19), including a role in inflammation.

that goes along with the chronic gut inflamation

   The stimuli that we found diminished PD-1 expression and function can, for the most part, be grouped together as ‘danger’ signals. However, the degree of concurrence delineated in this study between stimuli that diminish PD-1 expression and danger stimuli is not perfect. Typical danger cytokines of IL-1{alpha}, IL-1ß and TNF{alpha} (6) had no effect on PD-1 expression, at least by themselves. Conversely, IL-4 produced dramatic reduction in PD-1 expression and is not always thought of as a ‘danger’ signal, although it shares important ‘danger’ characteristics (19), including a role in inflammation (20,21).  Danger signal-triggered reduction of PD-1 expression fits with a speculative model for the function of PD-1 in normal and aberrant immune responses.

       

Offline gvcmdny

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  • Posts: 22
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #7 on: June 29, 2007, 11:23:51 PM »
very interesting, do you have more information about PD-1? I found this article but I am sure you already did a little more research in this matter.

http://www.jem.org/cgi/content/full/203/10/2281


BTW, I enjoy your constructive approach and your posts.

Offline bimazek

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  • Posts: 781
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #8 on: June 30, 2007, 04:40:38 PM »
thanks gvcmdny it means alot to me to hear that, i have only been poz for a year and am very scared and upset, emotionally devistated, had many friends, lovers, etc pass in last 25 years

so i am trying to make my little small humble contribution

of hope

Offline gvcmdny

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  • Posts: 22
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #9 on: June 30, 2007, 11:45:27 PM »
bimazek, I know that many person already said to you, stay calmed, don't worry, everything will be alright, etc. I won't repeat the same words, I do agree with all of them. My only suggestion would be to you, every time you feel upset and emotionally down, you are releasing a lot of noradrenaline in your bloodstream together with other vasoconstrictives and believe you me it's not worthy. being hiv positive is not a death sentence, bad thing happened, but you are young and you can fight it. just try to protect yourself, whenever you will have you private moments, just keep in mind not to get re-infected. your body is fighting, trust me. a human organism is the perfect "pharmaceutical" factory. today's science still tries to copy a natural defense pathways, I know that soon there will be history the hiv. just consider your medical condition like temporary pain in the neck. I will try to post more medical information regarding new promising scientific discoveries in the field. just stay focused on yourself, eat healthy food, help to your body to fight back, try to do not get angry in anything, just think in that moment if the issue you are getting upset will be so important after 10-20 years? probably not, take timely your meds, you don't want to give a virus the battle without fight.

peace to you my friend.

Offline frenchpat

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  • Love your friends, don't eat them.
Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #10 on: July 01, 2007, 02:47:14 AM »
just consider your medical condition like temporary pain in the neck.

 ??? is this what is called "a figure of speech?"

Pat
People have the power - Patti Smith

Offline gvcmdny

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Re: Breakthru Diagram shows CD8 LTNP info presented New most advanced
« Reply #11 on: July 01, 2007, 08:50:15 AM »
no pat, it's one human communicating with another.

 


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