As most have noticed, I am convinced that stress and inflammation interact to produce PD. This from this morning's Science Daily News adds to the picture-

".... researchers from the University of Connecticut Health Center have found that the same part of our nervous system that is responsible for the fight-or-flight response (called the sympathetic nervous system) also controls regulatory T cells, which are used by the body to end an immune response once a foreign invader has been removed or destroyed."

Here, in a nutshell, we have it.
1- The "f-o-f" response is triggered by stress
2- This affects the sympathetic nervous system which leads to poor control of T-cells
3- T cells thus become unable to end the response of the microglia in the inflammatory brain. Result is dead neurons and a sea of cytokines

It isn't an autoimmune situation where the immune system attacks our own tissues. It is a loss of the shutdown power of the T cells that are supposed to be under the control of the same part of the nervous system which responds to stress. The endocrine system pumps out cortisol in response to two things here (there are others). One, it pumps it out in response to chronic stress, the type we can't escape. Two, it pumps it out in response to inflammation, the original steroid treatment.

This would lead one to expect that cortisol levels in PWP would reflect all this.


1. Acta Neurol Scand. 1998 Feb;97(2):77-85.

Cortisol is higher in parkinsonism and associated with gait deficit.

Charlett A, Dobbs RJ, Purkiss AG, Wright DJ, Peterson DW, Weller C, Dobbs SM.

Statistics Unit, Public Health Laboratories Service, London, UK.

INTRODUCTION: We propose an active pathogenic mechanism, involving circulating
cortisol, in parkinsonism. MATERIALS AND METHODS: Serum cortisol was measured in
96 subjects with idiopathic parkinsonism, 170 without, and in 17 spouses and 36
siblings of elderly sufferers with double the number of controls, all obeying
inclusion/exclusion criteria. RESULTS: Cortisol, adjusted for sampling time, was
greater (17%, on average, P<0.001) in parkinsonians, but not in relatives. The
central cortisol lowering effect of anti-muscarinics was seen (P=0.025).
Selegiline may attenuate the disease, and parkinsonism is less frequent in
tobacco smokers. Selegiline was associated with a lower cortisol (P=0.03):
chronic smoking appeared (P=0.08) to be, irrespective of parkinsonism. Bowel
stasis has been implicated in the pathogenesis: cortisol was higher in
parkinsonians requiring laxatives (P=0.05). In controls, cortisol was lower, the
longer the stride (P=0.02): in parkinsonians, this relationship was numerically
reversed. A similar (P=0.01) group performance interaction was seen for
deterioration, over 4 years, in gait. CONCLUSION: Cortisol is doing harm or
mirroring something which is. A common pathway for neuronal protection/rescue
emerges.

PMID: 9517856 [PubMed - indexed for MEDLINE]

So the "regulatory T cells" are the guys who are supposed to tell the immune system to chill out. They get their orders from a part of the nervous system that also has a big role in fight or flight response (mainly endocrine system). If the f or f response get messed up, it could be because that control part of the nervous system has problem, the same part that also orders the regulatory T cells to take a message to the immune system to back off if, for example, the brain is being damaged. But what if there is a shortage of T cells to carry the message?

We have often heard that traumatic events preceeded our first symptoms. Well, according to the following, traumatic events cut the number of T cells available to carry the cease and desist orders by HALF. So, when I stood in the rain watching my home burn down 25 years ago, if I was barely controlling a hyperactive immune system in my brain and I suddenly lost half the messengers needed to maintain control, it might jjust be that that was when the fire got out of control....

Brain Behav Immun. 2009 Nov;23(8):1117-24. Epub 2009 Jul 18.
Substantial reduction of naïve and regulatory T cells following traumatic stress.

Sommershof A, Aichinger H, Engler H, Adenauer H, Catani C, Boneberg EM, Elbert T, Groettrup M, Kolassa IT.

Division of Immunology, University of Konstanz, Konstanz, Germany.

Posttraumatic stress disorder (PTSD) is associated with an enhanced susceptibility to various somatic diseases. However, the exact mechanisms linking traumatic stress to subsequent physical health problems have remained unclear. This study investigated peripheral T lymphocyte differentiation subsets in 19 individuals with war and torture related PTSD compared to 27 non-PTSD controls (n=14 trauma-exposed controls; n=13 non-exposed controls). Peripheral T cell subpopulations were classified by their characteristic expression of the lineage markers CD45RA and CCR7 into: naïve (CD45RA(+) CCR7(+)), central memory (T(CM): CD45RA(-) CCR7(+)) and effector memory (T(EM): CD45RA(-) CCR7(-) and T(EMRA): CD45RA(-) CCR7(-)) cells. Furthermore, we analyzed regulatory T cells (CD4(+)CD25(+)FoxP3(+)) and ex vivo proliferation responses of peripheral blood mononuclear cells after stimulation with anti-CD3 monoclonal antibody. Results show that the proportion of naïve CD8(+) T lymphocytes was reduced by 32% (p=0.01), whereas the proportions of CD3(+) central (p=0.02) and effector (p=0.01) memory T lymphocytes were significantly enhanced (+22% and +34%, respectively) in PTSD patients compared to non-PTSD individuals. To a smaller extent, this effect was also observed in trauma-exposed non-PTSD individuals, indicating a cumulative effect of traumatic stress on T cell distribution. Moreover, PTSD patients displayed a 48% reduction in the proportion of regulatory T cells (p<0.001). Functionally, these alterations were accompanied by a significantly enhanced (+34%) ex vivo proliferation of anti-CD3 stimulated T cells (p=0.05). The profoundly altered composition of the peripheral T cell compartment might cause a state of compromised immune responsiveness, which may explain why PTSD patients show an increased susceptibility to infections, and inflammatory and autoimmune diseases.

PMID: 19619638 [PubMed - indexed for MEDLINE]

I continue to think information about the plasticity of T cells is an important part of the puzzle. this is from a former posting:
http://neurotalk.psychcentral.com/sh...lls#post494294

http://www.newscientist.com/article/...ne-system.html
Can we reprogram the immune system?
28 January 2009 by Linda Geddes


http://www.newscientist.com/article/...ne-system.html

summary of 2 separate studies concerning immune cells
which has direct implication for the use of vaccines (at least in vitro), and why they
may result in dire effects.

immune system more flexible than previously
thought? T-helper (Th) cells "thought to be of 2
types: Th1 which sent viruses and bacteria from host cells and Th2
cells that fought parasites and bacteria in blood in other body
fluids and also fought allergens." 2 new classes of cells were
discovered: "regulatory T cells (T-regs) which attenuate the immune
system response and Th17 cells that trigger inflammation and
autoimmunity. Problem with this categorization was discovered when
the T-regs behaved like Th1 cells when the T-regs cells were exposed
to the molecules that normally result in a Th response. "(Immunity,
COI:10:1016/j.immuni.2008.12.009)...

Whoops--

In addition, study by Casey Weaver at Univ of Alabama showed
that "Th17 cells can also morph into Th1-like cells" under certain
conditions. Article concludes that "if Th1 cells are equally flexible
vaccines may not work as they are intended, says Christopher Wilson
of the Univ of Washington State in Seattle. For instance, if a
vaccine against a virus triggers a Th1 response but the Th1 cells
change their identity for some reason, 'the pathogen might yet
subvert the protection induced by the vaccine,he says"...

Occurs to me, if this happens in other than a petri dish, vaccines may result in immune responses in which
the correct immune cell morphs into the wrong cell--causing
inflammation or autoimmunity when none was wanted.......author cites
the safety study in which 6 individuals in Northwick park hosp in
london in March, 06, were given a drug that was to activate T-reg
cells, but instead they were made seriously ill. author notes that "there may be serious implications for immunotherapy trials in which T-regs are injected into people with autoimmune disease to dampen their immune response"...Perhaps the T-regs
morphed into Th17 causing an autoimmune response????

AND
breaching the blood brain barrier



FYI--
http://www.the-scientist.com/blog/display/55517/
Posted by Edyta Zielinska
Researchers have identified a novel mechanism by which immune cells wiggle their way across the blood-brain barrier in diseases such as multiple sclerosis (MS). A type of T-cell involved in autoimmune disease leads the way, entering the brain and perhaps priming the blood-brain barrier's membrane to attract other immune cells -- opening the door for those cells to do their inflammatory damage, according to a study published online yesterday (Mar 22) in Nature Immunology.

Olsen, thanks for sharing all of this....I can't help but wonder if the PD rates began to increase after vaccination began en masse here. In other words, Rick links it to the industrial revolution....and perhaps. But what about when the massive vaccination program for kids really got under way....my generation, born in the 60s? My parents didn't have those shots, and yes, they have PD and Alz., but seems like in much lower numbers, and no one I know from that generation was early onset.

This concern is compounded by the research I have read about the gardasil vaccine for girls, after which many girls have died, become paralyzed very soon thereafter (days, weeks, a month) or fainted immediately after getting the shot. The fainting was so bad that a warning was sent out to doctors to administer the shot with the girl lying down so she wouldn't faint! And yet where was this in the news?

I cannot believe something in that vaccine is not going directly into the brain to make those girls faint as soon as the shot is given. So what is the effect of cumulative shots, given at birth and before the BBB is really developed to protect that new brain....? Decades later, I believe, we see the damage that was done by those vaccines, the number, the age at which they are given, the ingredients, everything.

I know the diseases we have vaccines for were already declining when those vaccines came out, due, as I have read, in large part to new found sanitation and clean water. It would be interesting to see the connection between PD and vaccination rates. I am guessing my kids' generation will have an even larger percentage of PD and related illness because of the even larger numbers of vaccines given to their generation, most of which were multiple virii in one shot instead of the one virus per shot that I got as a kid. What will big pharma possibly have to say then?

This article is a couple of years old and you may have already seen it.......

Originally published online as doi:10.1189/jlb.0507296 on August 3, 2007

Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson’s disease

(Journal of Leukocyte Biology. 2007;82:1083-1094.)
© 2007 by Society for Leukocyte Biology
Ashley D. Reynolds*,{dagger}, Rebecca Banerjee*,{dagger}, Jianou Liu*,{dagger}, Howard E. Gendelman*,{dagger},{ddagger},1 and R. Lee Mosley*,{dagger}

* Center for Neurovirology and Neurodegenerative Disorders, Departments of
{dagger} Pharmacology and Experimental Neuroscience and
{ddagger} Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA

ABSTRACT

Progressive loss of dopaminergic neurons in the substantia nigra pars compacta and their terminal connections in the striatum are central features in Parkinson’s disease (PD). Emerging evidence supports the notion that microglia neuroinflammatory responses speed neurodegenerative events. We demonstrated previously that this can be slowed by adoptive transfer of T cells from Copolymer-1-immunized mice administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) recipients. The cellular basis for this neuroprotective response was the CD4+ T cell population, suggesting involvement of CD4+CD25+ regulatory T cells (Tregs), cells known to suppress immune activation and maintain immune homeostasis and tolerance. We show for the first time that adoptive transfer of CD3-activated Tregs to MPTP-intoxicated mice provides greater than 90% protection of the nigrostriatal system. The response was dose-dependent and paralleled modulation of microglial responses and up-regulation of glial cell-derived neurotrophic factor (CDNF) and TGF-β. Interestingly, that adoptive transfer of effector T cells showed no significant neuroprotective activities. Tregs were found to mediate neuroprotection through suppression of microglial responses to stimuli, including aggregated, nitrated {alpha}-synuclein. Moreover, Treg-mediated suppression was also operative following removal of Tregs from culture prior to stimulation. This neuroprotection was achieved through modulation of microglial oxidative stress and inflammation. As Tregs can be modulated in vivo, these data strongly support the use of such immunomodulatory .............contd