Thanks for posting on PANDAS and autoimmunity.
We have discussed these hypotheses several times here and it seems like we can connect PD, infection, inflammation and autoimmunity very well. For those of you interested in this topic, here I go again.

Immunologists use the phrase “Molecular Mimicry” to connect infections with the onset of autoimmune diseases.
Check out Molecular Mimicry http://www.direct-ms.org/molecularmimicry.html for an excellent explanation.

PD fits into this paradigm as well as any autoimmune disorder. If anyone is interested in digging deeper, send me a mail.

“The concept of molecular mimicry is simple but entails a lot of understanding of the workings of the immune system. Basically molecular mimicry means that part of a molecule of a given protein closely resembles a part of another totally different protein.

Proteins are made up of strings of amino acids and in molecular mimicry one series amino acids(eg~10) in one protein is very similar to a string of ten amino acids in another protein. "
To understand how molecular mimicry works in the induction of autoimmunity one must understand the basic mechanisms of an immune responses.

Step 1: What does the immune system see in an infection? When you have an infection, for eg., with influenza virus, your immune system does not look at the whole virus, it recognizes just a part of the protein portion of the invader. It does this with T cells with receptors that bind to short segments(~10 amino acids) of a foreign protein. This short segment of aminoacids is like a name tag or a thumb print of a pathogen.

Step 2: How do you get these small segments of patosgen and what do they do? During an infection, cells called macrophages engulf a foreign invader(eg a bacteria or virus) and break it down into fragments. These fragmented viral antigens are recognized by “T cells” circulating in the body. (It is called antien presentation)

Step 3: What do T cells do? T cells are like good soldiers, they go to the site of infection, make all sorts of cytokines and kill infected cells.

Step 4: How does a T cell recognize infected cell? For T cells, infected cells are those that display the “name tag” (10 amino acid string of the viral protein). If infected cells fail to show their name tag, T cells cannot kill them and vice versa. This is the interesting part. If cells display the name tag, but are not infected and perfectly alright, T cells still attack them and kill them.

Let me put this theory in the context of PD:

Influenza infection generates T cells specific to name tag A
PD onset starts with misfolded proteins (eg., alpha-syn) and neurons try to get rid off it by chopping down (autophagy is the technical term). Defects in this process due to genetic mutations (UCHL-1) do contribute to PD. A combination of defective protein and defective autophagy could lead to generation of small strings of amino acids resembling viral name tag A. Net result is that now neurons are displaying the name tag A, though they are not infected with influenza.
Clumps of alpha-syn also generate neuroinflammation.
T cells notice inflammatory signals and enter brain. There are plenty of neurons displaying name tag A and T cells get busy with cytokines and killing all the “infected cells”.
This is how I see infection, PD and autoimmunity fitting together. There are well established methods to test these hypotheses………….may be some day it would be tested

Girija