Sunday, 22 October 2017

What is programmed death 1?

This is about a protein expressed by the immune system. It is a protein involved in limiting the immune response.



This post is going to be hard to understand unless you click on the links in this post and do some reading.

PD-1 is known as an immune checkpoint, which is a molecule in the immune system that either turn a signal (co-stimulatory molecules) or turn down a signal.

However, you need to know this to read the next post.


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There are many other immune checkpoints:

Four stimulatory checkpoint molecules are members of the 
CD27. This molecule supports antigen-specific expansion of na├»ve T cells and is vital for the generation of T cell memory. CD27 is also a memory marker of B cells. 
CD40. This molecule, found on a variety of immune system cells including antigen presenting cells This is expressed on B cells
CD122. This molecule, which is the Interleukin-2 receptor beta sub-unit, is known to increase proliferation of CD8+ effector T cells. This is expressed on memory B cells
OX40. This molecule, also called CD134, has OX40L, or CD252, as its ligand. Like CD27, OX40 promotes the expansion of effector and memory T cells, however it is also noted for its ability to suppress the differentiation and activity of T-regulatory cells, and also for its regulation of cytokine production. It is only upregulated on the most recently antigen-activated T cells within inflammatory lesions.This is expressed by B cells

This may be relevant to the effect of anti-TNF that can make MS worse as it shows that TNF is very important in the life and Dead of B cells. Anti-TNF makes memory cell survive, is this why it is bad for MS. However, it could also kill other B cell populations.

There are another two stimulatory checkpoint molecules that are members of the CD28 family:
ICOS. This molecule, short for Inducible T-cell costimulator, and also called CD278, is expressed on activated T cells. Its ligand is ICOSL, expressed mainly on B cells and dendritic cells.)This is expressed by B cells.
CD28. This molecule is constitutively expressed on almost all human CD4+ T cells and on around half of all CD8 T cells. Binding with its two ligands are CD80 and CD86, expressed on dendritic cells, prompts T cell expansion.  This is expressed on memory B cells.
There are inhibitory check points:
A2AR. The Adenosine A2A receptor 
B7-H3, also called CD276,
B7-H4, also called VTCN1, 
BTLA. This molecule, short for B and T Lymphocyte Attenuator and also called CD272. 
CTLA-4, short for Cytotoxic T-Lymphocyte-Associated protein 4 and also called CD152
IDO, short for Indoleamine 2,3-dioxygenase, is a tryptophan catabolic enzyme with immune-inhibitory properties. 
KIR, short for Killer-cell Immunoglobulin-like Receptor, is a receptor for MHC Class I molecules on Natural Killer cells. Bristol-Myers Squibb is working on Lirilumab, a monoclonal antibody to KIR.
LAG3, short for Lymphocyte Activation Gene-3, works to suppress an immune response by action to Tregs[ as well as direct effects on CD8+ T cells.[36] Bristol-Myers Squibb is in Phase I with an anti-LAG3 monoclonal antibody called BMS-986016.
PD-1, short for Programmed Death 1 (PD-1) receptor, has two ligands, PD-L1 and PD-L2
TIM-3, short for T-cell Immunoglobulin domain and Mucin domain 3, expresses on activated human CD4+ T cells and regulates Th1 and Th17 cytokines.[
VISTA (protein), Short for V-domain Ig suppressor of T cell activation, VISTA is primarily expressed on bone marrow-derived cells


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Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a cell surface receptor that plays an important role in down-regulating the immune system and promoting self tolerance, so you block autoimmunity by suppressing T cell inflammatory activity. PD-1 is an immune checkpoint and guards against autoimmunity through a dual mechanism of promoting apoptosis (programmed cell death) in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells).
So PD-1 inhibits the immune system. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.

Over-expression of PD1 on CD8+ T cells is one of the indicators of T-cell exhaustion 




T-cell exhaustion is the progressive loss of T-cell function. It can occur after infections.

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