Protective Autoimmunity
Kumar
Can you tell me about protective autoimmunity in case of damage to CNS
due to spinal injury at C5 level?
Can immune or autoimmune response be beneficial in these cases?
Best wishes.
John Hasenkam
processes were protective in secondary injury. Generally though, inhibiting
immune responses appears beneficial with the initial injury.
John.
The Journal of Neuroscience, July 1, 2001, 21(13):4564-4571
Neuronal Survival after CNS Insult Is Determined
by a Genetically Encoded Autoimmune Response
Jonathan Kipnis, Eti Yoles, Hadas Schori, Ehud Hauben, Iftach Shaked, and
Michal Schwartz
Department of Neurobiology, The Weizmann Institute of Science, 76100
Rehovot,
Israel
Injury to the CNS is often followed by a spread of damage (secondary
degeneration), resulting in neuronal losses that are
substantially greater than might have been predicted from the severity of
the primary insult. Studies in our laboratory have shown
that injured CNS neurons can benefit from active or passive immunization
with CNS myelin-associated antigens. The fact that
autoimmune T-cells can be both beneficial and destructive, taken together
with the established phenomenon of genetic
predisposition to autoimmune diseases, raises the question: will genetic
predisposition to autoimmune diseases affect the
outcome of traumatic insult to the CNS? Here we show that the survival rate
of retinal ganglion cells in adult mice or rats after
crush injury of the optic nerve or intravitreal injection of a toxic dosage
of glutamate is up to twofold higher in strains that are
resistant to the CNS autoimmune disease experimental autoimmune
encephalomyelitis (EAE) than in susceptible strains. The
difference was found to be attributed, at least in part, to a beneficial
T-cell response that was spontaneously evoked after CNS
insult in the resistant but not in the susceptible strains. In animals of
EAE-resistant but not of EAE-susceptible strains devoid of
mature T-cells (as a result of having undergone thymectomy at birth), the
numbers of surviving neurons after optic nerve injury
were significantly lower (by 60%) than in the corresponding normal animals.
Moreover, the rate of retinal ganglion cell survival
was higher when the optic nerve injury was preceded by an unrelated CNS
(spinal cord) injury in the resistant strains but not in
the susceptible strains. It thus seems that, in normal animals of
EAE-resistant strains (but not of susceptible strains), the injury
evokes an endogenous protective response that is T-cell dependent. These
findings imply that a protective T-cell-dependent
response and resistance to autoimmune disease are regulated by a common
mechanism. The results of this study compel us to
modify our understanding of autoimmunity and autoimmune diseases, as well as
the role of autoimmunity in non-autoimmune
CNS disorders. They also obviously have far-reaching clinical implications
in terms of prognosis and individual therapy.
Key words: protective autoimmunity; encephalitogenicity; neuroprotection;
autoimmune disease; CNS; EAE
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134564-08$05.00/0
"Kumar" <lordsh...@gmail.com> wrote in message
news:4198d158-1f8e-4b82...@k36g2000pri.googlegroups.com...
Kumar
> Yes, there was a J of Neuroscience study which highlighted how autoimmune
> processes were protective in secondary injury. Generally though, inhibiting
> immune responses appears beneficial with the initial injury.
>
> John.
>
> The Journal of Neuroscience, July 1, 2001, 21(13):4564-4571
>
> Neuronal Survival after CNS Insult Is Determined
>
> by a Genetically Encoded Autoimmune Response
>
> Jonathan Kipnis, Eti Yoles, Hadas Schori, Ehud Hauben, Iftach Shaked, and
>
> Michal Schwartz
>
> Department of Neurobiology, The Weizmann Institute of Science, 76100
> Rehovot,
>
> Israel
>
> Injury to the CNS is often followed by a spread of damage (secondary
> degeneration), resulting in neuronal losses that are
>
> substantially greater than might have been predicted from the severity of
> the primary insult. Studies in our laboratory have shown
>
> that injured CNS neurons can benefit from active or passive immunization
> with CNS myelin-associated antigens. The fact that
>
> autoimmune T-cells can be both beneficial and destructive, taken together
> with the established phenomenon of genetic
>
> predisposition to autoimmune diseases, raises the question: will genetic
> predisposition to autoimmune diseases affect the
>
> outcome of traumatic insult to the CNS?
>
> > Can you tell me about protective autoimmunity in case of damage to CNS
> > due to spinal injury at C5 level?
>
> > Can immune or autoimmune response be beneficial in these cases?
>
>
> - Show quoted text -
Thanks a lot. Actually I also tried by reading such type of studies.
Does it suggest that, on initial injury to CNS, active immune system
can cause greater damage than real insult? Glial scar formation can be
important outcome from such immune response or from medication
programme. It may be difficult to reverse formed glial scars after
insult, basic importance can be that, 1. scars are not formed at
initial stage of insult to CNS 2. if formed, how it can be removed
enabling nerve regenaration. Can initial immune response inhibit glial
scar formation and can autoimmune response remove formed glial scars
at some time after insult to encourage nerve regeneration?
This understanding looks to be quite important for understanding
natural or mediacated recovery to CNS injuries.
Btw, how many people recover on its own after some time of initial
insult to CNS injury of C5 level?
John Hasenkam
-----
Generally suppression of the immune response appears to confer benefit.
It *may* be possible to prevent glial scar formation via inhibition of
chondroitin sulfate, I recall one study which demonstrated that. I doubt it
will be that simple.
Reversal of glial scars is highly unlikely.
You are correct, this is very important in regards to CNS injury but we are
a long way from clinical applications.
We do not know how many people recover from CNS injury. Rates of recovery
vary quite a bit.
Kumar
> "Kumar" <lordshiva5...@gmail.com> wrote in message
>
> - Show quoted text -
Yes, supression of immune system by steroid drugs appears to reduce
the damage to nerve cells and may be in regular practice. However I am
also trying to look on possibilty of survival benefits from initial
immune responses & secondary immune or autoimmune responses. Let us
assume that if an injured person is quite healthy and young in age
and if no manipulation/intervention is pursued to natural immune
responses(at initial and later stages) but patient just maintained,
what can be the fate of patient?
Btw, are there some similarities in multiple sclerosis and nerve
damage due to spinal injuries?
Best regards.
John Hasenkam
It is one thing to read these studies and it is another world to apply these
results in clinical practice. Individuals vary greatly in their physiology.
I don't think any physiological intervention will be of benefit. Physical
therapy might help.
Similiarities with MS? Doubtful.
Kumar
>
> - Show quoted text -
Thanks again.
Inflammatory, immune and autoimmune responses are own body pursued
mechanisms probably mostly for survival purpose(except transplant
cases). How can it be considered for sure that these can be harmful to
body unless manipulated as suppressive or excessive? In this thought,
can't immunosuppressive manipulations be bit odd?
John Hasenkam
Thanks again.
---------
Yes, it is odd but it is also a fact. Don't let theory, particularly broad
theories, interfere with facts in specific cases. I also have wrestled with
the issue as to why inflammation is such a problem. This can be understood
but that is a very long story. Firstly, you need to set aside the idea that
evolution has "finished the job". Not at all, evolution doesn't really
"finish" anything. It is blind and simply allows survival for those with a
current advantage. The primary function of the immune system is fighting off
pathogens. It is a trade off, in performing this role it very often damages
healthy tissues. It is that or die. Conversely, those who seek to suppress
inflammation to the greatest degree possible are making a bad mistake, for
even the term "inflammatory mediators" is quite misleading. These so called
agents play a role in everything from inflammation to neurogenesis to muscle
repair. "Inflammation" is absolutely essential to health. I used to refer to
inflammation as growth gone wild. There is some sense to that. Autoimmunity
as a protective process only makes sense in the context of "Danger Theory".
See this link:
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/dangertheory.html
Incidentally, very good immuno related website.
Again though, I am being very simplistic here, it takes a long time to
explain all this.
Kumar
>
> Incidentally, very good immuno related website.
>
> Again though, I am being very simplistic here, it takes a long time to
>
> - Show quoted text -
Many thanks.
Still with every action be defence system, we should try best to find
surrvival advantage. Look at following site. It may indicating that
iron withholding can be in surrvival benefit:-
http://www.cdc.gov/ncidod/EID/vol5no3/weinberg.htm
Let us look cases of diabetic type2(with isulin resistance). Insulin
(endo/exo genous) can be exposed in excess to target cells. Target
cells can opt down regulation of insulin receptors from consistent
over-exposure. Other actions of insulin can also be enhanced. As such,
can't body defence take it is as persistent over exposure of insulin,
so better prefer to damage some beta cells by triggering autoimmunity
to beta cells either permanentaly or to be regenarated later when such
exposure is normal? As such other immune/inflammatory mechanisms, if
naturally followed should be having some survival purpose in net
benefit(may be at some cost). On CNS injury, can't such inflammatory
response be ment to keep injury alive to avoid scar formation? If
scars formed, can't autoimmunity afterwords be ment to remove these
scars(scars are own body substances) and try healing without scar? We
just have to see, can initial immune/inflammatory response, while
doing excessive damage, also heal injury without scars? Can secondary
autoimmune response remove scars to progress for healing? If people
with CNS injury got healed after some time, my thoughts can be bit
indicative. Best regards.