free radicals

[psyuk]

i was on another forum, and this guy, probably a premed, said,

"plus your immune system gets rid of these (extracellular) free radicals as well."

how is this possible?

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[psyuk]

he then goes on to say

"there are a wide variety of theories out there and all have not be conclusive, but pieces of the puzzle and current belief leads up to believe that there is a direct corellation to immune complex and to teh deactivation of free radicals.

its been 3 years since i've taken undergraduate biochemistry so this is all committed to memory.."

 

[zep]

Psyuk: I?m no immunologist but I think I may know where this person was coming from (perhaps erroneously?).

There are two things about the immune system that may lead one to believe that it is a big scavenger of free radicals. The first is that the endothelial reticular system is loaded with ?scavenger receptors? that bind to modified proteins, including oxidized proteins, i.e., oxidized LDL. There is a have huge diversity in the ligands that scavenger Rs can bind (very odd for a true receptor). So it is possible that because they bind up modified/damaged proteins, that one may think this equates to scavenging free rads. But to my knowledge, there is no ?free radical receptor? in the immune system, or anywhere in the body for that matter, only enzymes that inactivate them (below).

The second thing is that macrophages, and in particular activated macrophages, have pretty high levels of catalase and peroxidase expression. This would suggest that macrophages are involved in degrading H2O2. So, I do think immune cells play a role in inactivating/scavenging free rads, but I don?t think it?s a major function of the immune system. Plenty of cells express these enzymes and can release them into the extracellular fluid.

Any other ideas out there? Now i'm curious.

 

[psyuk]

this is his reason:

"These immune cells release, cytokines, haptens, immunogens, and interferons (as well as other factors that play a part in the immune complex.) Cytokines, haptens, immunogens and interferons all play a role in the production of free radicial reduction. so if you put the two together, we can hypothesize that the two are related (which may or may not be the case). There have been numerous studies discounting this idea, but then again there are very many studies that do stand behind this idea (more so than not)."



how in the world do "these immune cells" release immunogens and haptens? is that even possible?

 

[tedrik]

The second thing is that macrophages, and in particular activated macrophages, have pretty high levels of catalase and peroxidase expression. This would suggest that macrophages are involved in degrading H2O2. So, I do think immune cells play a role in inactivating/scavenging free rads, but I don?t think it?s a major function of the immune system.

I don't know about the question of the immune system's response to free radicals, but if a macrophage degraded H2O2, wouldn't it create an oxygen free radical?

 

[zep]

I don't know about the question of the immune system's response to free radicals, but if a macrophage degraded H2O2, wouldn't it create an oxygen free radical?

No. Catalase generates molecular oxygen:

2 H2O2 > 2 H2O + O2

Peroxidase uses H2O2 as the electron acceptor to catalyse a bunch of 2e-oxidative reactions. The heam Fe gets oxidized and H2O2 is reduced to H2O; there is a radical intermediate but I dont think it is liberated. The other protective mechanism against oxy rads is SOD - this dismutates superoxide to H2O2 and O2. The radicals are mostly generated from reduction of O2 to H2O.

I'm no biochemist, so someone please correct me if i'm wrong here.

 

[zep]

Actually I should be more clear on this. Glutathione peroxidase converts H2O2 to O2 + H2O and myeloperoxidase generates hypochlorous acid from H2O2. (I think its HOCl, but that may not be right...I need to check.) Either way, the product is a strong oxidant from what I remember.

The OH radical is the major PITA and it comes mostly from the Fenton Reaction (H2O2 + Fe > OH radical + Fe).

I still don't follow the logic that psyuk presented from the other poster. Maybe I'm missing something too.

 

[psyuk]

partial transcript

X: you had better be more careful choosing sources. the media usually blows things out of proportions. I mean you would have to consume an excess of 400 lbs of the actual burned portion annually for 10 years to have a 40% risk of cancer. risk is all relative too, since the human genome is very elegant and complex. the DNA code for proteins that code for enzymes that breakdown your toxic materials. Since DNA is different for every individual is different many polymorphisms of these enzymes in your liver, an example is CYP2D6 is the enzyme responsible for getting rid of most (37-75%) of the toxic chemicals that enter your body (burned food, bbq = arsenic, lead, CO, FeO, O-, etc)

plus your immune system gets rid of these free radicals as well.

so unless you have Mid-stage HIV, Lupus or a predisposition or history of cancer

go ahead, indulge yourself.


New England Journal of Cancer, Volume 14, Supplement 1, March 1999, Pages S47-S61
BB Ely. LC. Koo. JH Kelly. XC. Ho.

Then again, the meat industry of america, and Ely Lilly funded this project.

psyuk: no, your immune system actually generates free radicals during induction of immune responses against foreign pathogens.

the antioxidase enzymes such as supersoxide dismutase, gluthione peroxidase, and methionine reductase, whose mechanism by which they are produced is not yet fully understood, serve as the main defense system in eliminating free radicals.

X: yes your immune system creates free radicals. but DOES IT RELEASE THEM SYSTEMICALLY? No! Cytotoxic-TH1-TH2-DTH T-cells have a mechanism that counteracts the event of immune cells releasing these peroxides they produce. they produce cytokines that inturn turn on the activation of these enzymes. Seriously, where do these enzymes come from? they are destroyed and made again constantly. your immune system, mechanisms help control what's needed and what's not, so acts as a regulator of these free radical catalases.

we have enzymes in your body superoxidase dismutase that gets rid of harmful free radicals. These mechanisms are fully understood, go out and check out lipincott's text to biochemistry. ALSO, red blood cells have a defense mechanisms to counteract free radicals by utilizing the hexosemonophosphate shunt or HMP shunt, PPP pathway whatever you wanna call it.

also gluthione is produced in the liver, methionine is produced in the liver.. superoxide dismutase is found in the blood and in extracellular space.

---------blah blah blah----------------

psyuk: yeah me too.

but you still havent answered my question:

how does the immune system eliminate free radicals?

give me sources as well.

X: These immune cells release, cytokines, haptens, immunogens, and interferons (as well as other factors that play a part in the immune complex.) Cytokines, haptens, immunogens and interferons all play a role in the production of free radicial reduction. so if you put the two together, we can hypothesize that the two are related (which may or may not be the case). There have been numerous studies discounting this idea, but then again there are very many studies that do stand behind this idea (more so than not).


most of the information is from immunology 4E, by Kuby and
harrison's principals of internal medicine

here are two links in case you don't have these two references handy.
http://www.whfreeman.com/immunology/INDEX.HTML
http://harrisons.accessmedicine.com/
i think most of the immunology stuff i used is in the chapters relating to B,T-cell activation, signaling.

i'll goto my office tomorrow and dig up those journal articles... i think its 2002, NEJM, title(i'm not too sure, but) Elimination of Free Radicals in immune compromised patients. (double blind, non-placebo controlled, demographics weighted, randomized (p<.01) study.)

---------blah blah blah-------
psyuk:

register here and let's talk: http://forums.studentdoctor.net/

thread: http://forums.studentdoctor.net/showthread...248#post1689248

 

[psyuk]

During lunch i asked some of my friends (2 tumor immunologists and a medical student) about this. They all said there's no proof that the immune system gets rid of free radicals.

thanks zep and tedrick for your contributions to this thread.