IL-10 Question

[Pox in a box]

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Why does IL-10 prevent delayed type hypersensitivity reactions? TH2 cells make it and they inhibit TH1 cells but what does this mean exactly in the simplest of terms?

 

[Janders]

Why does IL-10 prevent delayed type hypersensitivity reactions? TH2 cells make it and they inhibit TH1 cells but what does this mean exactly in the simplest of terms?

Delayed type hypersensitivity is a cell mediated immunity, and Th1 cells need to help this process along. Like you said, IL-10 inhibits Th1 cells... so there you go 🙂

 

[omarsaleh66]

There are 2 types of T helper cells like u said : Th1, Th2

1) Th1 cells produce:

a)

IFN-y (this will activate the macrophages and I think inhibits Th2 cells like IL-10 inhibits Th1, not positive about this)

IL-2
TNF-a

b)

These things that are produced by Th1 produce and they do Delayed Hypersensitivity (Type 4):

Macrophages
NK cells
CD8+ Cytolytic T Cell







2) Th2 make:

IL-4
IL-5
IL-6
IL-10 (as u said this inhibits Th1)

and these produce the Hypersenitivity Type 1-3:

B cell proliferation
Plasma cell differentiation

 

[fang]

Why does IL-10 prevent delayed type hypersensitivity reactions? TH2 cells make it and they inhibit TH1 cells but what does this mean exactly in the simplest of terms?

After an inital exposure to an antigen, memory T-cells, remain in circulation. These cells release lymphokines in response to exposure to the same antigen that activated them in the past. The circulating cells that initiate the hypersensitivity reaction are TH1 cells.

If an antigen presenting cell (like a dendritic cell in the skin that has encountered TB antigen) presents that antigen to one of these circulating TH1 cells, it will secrete:
1. IL-2 -- initiate growth of more helper and cytotoxic T cells
2. IFN-gamma -- activates macrophages (macrophages fuse to become langerhans cells in granulomatous inflammation), activates NK cells, and TURNS OFF the TH2 response (limits the response)
3. TNF-beta -- activates macrophages, attracts neutrophils, increases the sensitivity of T cells to IL-2

Appearantly, the response is not fast or robust enough to produce a visible reaction if the T cells have never been exposed to the antigen in the past.

So, since the circulating cells that mediate this response are the (IL-10-sensitive) TH1 cells, inhibiting them will diminish the reaction.

 

[Pox in a box]

Okay guys. You lost me. I need simple.

 

[fang]

Okay guys. You lost me. I need simple.

I think the main point is that it's the TH1 cells, not TH2 cells, that react to antigen during a type IV. As you know, IL-10 inhibits TH1 cells. Just remember you have to have been exposed to the antigen in the past to have a type IV reaction-- that's the basis for the TB skin test.

 

[Janders]

Okay guys. You lost me. I need simple.

OK, lets go from the beginning.

Type IV hypersensitivity, aka Delayed type hypersensitivity, is an immune reaction involving the Cellularly Mediated branch of immunity. This includes Th1 Cells, Macrophages, NK Cells and their buddies. It works like this:


An antigen (the classic one is tuberculin skin test antigen) somehow gets into the body. It is picked up by presenting cells, like a dendritic cell. This dendritic cell holds it up (via an MHC2 molecule). A CD4 tcell that is cruising around sees this evil antigen, and binds it.

THis binding involves fun things like MHC II, CD4, and TCR.

Now, the cd4 cell (aka the Th0 cell!), due to reasons not fully understood but probably involving cytokines and cell-to-cell interactions, has to decide to become either a th1 cell or a th2 cell. If it becomes th1 it will activate the cell mediated immune system, if it goes the th2 route, humoral immunity will be activated.

In this case it decides to go the CMI route and become a th1 cell. It then secretes IFN-gamma. This is the most important thing it secretes. IFN gamma activates macrophages. IFN gamma, along with co-secreted IL-2 and TFN-beta activate Cytotoxic cd8 cells and natural killer cells. You can think of the the th1 cell as the commander that orders all these troops into battle. IFN-gamma does one more important thing, it INHIBITS any nearby Th2 cells. This is so that the cell mediated immunity can go forward full throttle, and no humoral immunity gets in the way.

So you can think of the antigen presenting cells as early warning radar, the th cell as the commander, and all the other cells as his soldiers.

Now, if the antigen had been a little different, the Th0 cell might have become a th2 cell. This would alter the counter attack significantly. Th2 cells secrete IL-2, 4, 5, 6, and 10. These serve in various ways to turn on Bcells and get them to secrete antibodies. IL-10 has another function, equivalent to IFN-gamma. It turns off any nearby th1 cells! That way the th2 cell can go humoral without any CMI getting in the way.

Moral of the story:
*Th1 cells want th2 to butt out of their way; they secrete IGN-gamma to turn th2 off.
*Th2 cells want th1 to butt out of THEIR way; they secrete IL-10 to turn th1 off.
*Delayed type hypersensitivity (type IV) is a function of cell mediated immunity. It needs th1 cells to command this immunity. If there is a ton of IL-10 around, the th1 one will be turned off, and no delayed hypersensitivity will occur.





(edit because I type like an idiot)

 

[p53]

An antigen (the classic one is tuberculin skin test antigen) somehow gets into the body. It is picked up by presenting cells, like a dendritic cell. This dendritic cell holds it up (via an MHC2 molecule). A CD4 tcell that is cruising around sees this evil antigen, and binds it.

Janders, nice try. A good explanation but a major flaw here. The Langerhans cell with the antigen is in the skin (hence the name skin test) migrates to the local lymph node. Once at the lymph node, with an antigen it is considered mature thus is named dendritic cell. The dendritic cell touches as many T- Cells in the lymph node with his thingy sticking out (MHC receptor with antigen) until he finds a partner that likes it (think of it as a guy at a bar hitting on every girl at the joint with his hands until the sleazy slut says yes i.e. MHC II/CD 4+ match). Then, this activated T cell goes back to the original site of the antigen via lymphatic duct to the left subclavian vein to the heart and then to the arterial circulation. Once it is in the microcirculation, it is homed into the site of action via selectins that were expressed due to activation of endothelial cells by the IL1 released by the couch potato macrophages also in the stromal tissue.

 

[Janders]

Yeah, in trying to keep it simple I certainly left out a lot. But good point, I'd hate to add to the confusion with oversimplification. Good job explaining the logistics of the antigen presentation!

 

[fang]

Thanks.

I thought Langhans cells were in the epidermis-- the cells migrating through CT are dendritic cells, so they'd be the ones to pick up a TB skin test.

 

[Pox in a box]

Guys, I'm going to have to skip town for a week (unless my hotel has internet access, hopefully!). Thanks for answering the question. I'm flying out tonight (hopefully I can get a lot accomplished).

 

[alhkim]

hey p53...Langerhans cells ARE dendritic cells--Janders explanation is correct. There are mature DCs (in the lymph nodes, like you said), and immature DCs, which reside in the periphery (i.e. skin, lungs, blood, etc). Langerhan cells are a specific type of DC where they reside in the epidermal-dermal skin junction (FYI, there are dermal layer residing dendritic cells, but they are not technically called Langerhans cells). Langerhans cell were originally named after a German medical student named Paul Langerhans in 1868, who was hunting for sensory nerve endings in the epidermis. He found these cells, but obviously they were not nerves.

FYI, I just graduated with my MD/PhD in immunology, looking at the role of DCs in CD8+ antiviral T cell responses. Not to hate or anything...just wanted to clear the air a little bit.

As for the IL-10 question, it was addressed earlier. IL-10 is a Th2 cytokine, inhibits Th1 responses (in reality, it appears that IL-10 suppresses DCs, macrophages, CD8+ T cells also).

Janders, nice try. A good explanation but a major flaw here. The Langerhans cell with the antigen is in the skin (hence the name skin test) migrates to the local lymph node. Once at the lymph node, with an antigen it is considered mature thus is named dendritic cell. The dendritic cell touches as many T- Cells in the lymph node with his thingy sticking out (MHC receptor with antigen) until he finds a partner that likes it (think of it as a guy at a bar hitting on every girl at the joint with his hands until the sleazy slut says yes i.e. MHC II/CD 4+ match). Then, this activated T cell goes back to the original site of the antigen via lymphatic duct to the left subclavian vein to the heart and then to the arterial circulation. Once it is in the microcirculation, it is homed into the site of action via selectins that were expressed due to activation of endothelial cells by the IL1 released by the couch potato macrophages also in the stromal tissue.

 

[p53]

hey p53...Langerhans cells ARE dendritic cells--Janders explanation is correct. There are mature DCs (in the lymph nodes, like you said), and immature DCs, which reside in the periphery (i.e. skin, lungs, blood, etc). Langerhan cells are a specific type of DC where they reside in the epidermal-dermal skin junction (FYI, there are dermal layer residing dendritic cells, but they are not technically called Langerhans cells). Langerhans cell were originally named after a German medical student named Paul Langerhans in 1853, who was hunting for sensory nerve endings in the epidermis. He found these cells, but obviously they were not nerves.

FYI, I just graduated with my MD/PhD in immunology, looking at the role of DCs in CD8+ antiviral T cell responses. Not to hate or anything...just wanted to clear the air a little bit.

As for the IL-10 question, it was addressed earlier. IL-10 is a Th2 cytokine, inhibits Th1 responses (in reality, it appears that IL-10 suppresses DCs, macrophages, CD8+ T cells also).

"The Langerhans cell with the antigen is in the skin (hence the name skin test) migrates to the local lymph node. Once at the lymph node, with an antigen it is considered mature thus is named dendritic cell."

What part of this did you not understand? I clearly stated that langerhans cells BECOME dendritic cells. For simple minds, they are about the same as a monocyte is to a macrophage. NOW TELL US IF THEY ARE NAMED MONOCYTES OR MACROPHAGES OUTSIDE THE BLOODSTREAM. Do you follow?

For someone with a poor grasp of BASIC immunology they are the same, for the rest of us that understand the mechanism, there is a reason it is renamed dentitic cell once it is in the lymph node. Obviously, if it isn't in the lymph node a dendritic cell than it is STILL a Langerhans cell. Gee, I wonder if they are the same cell? Anyone with a HIGH SCHOOL logic ability can figure that out.

As for the comment about MD/PhD. You are not going to get anyone to kiss your butt. YOU CAN'T ACHIEVE EXPERT WITNESS STATUS BY BOASTING YOUR TITLE ON SDN. On SDN where anonymity reigns, checks and balances by fellow members overrules a title that Y0U hold in high regard. We don't give a damsel if you are a MD/PhD or a high school dropout, if you post knowledge about something and it is reinforced by the literature than knowledge trumps Title.

Also, we all know when you study for a PhD you specialize. When you specialize it is likely that you tend to forget about the basics. I recommend you reread Janeway Immunology on Cell mediated response and come back with a book report. Let's face it, between the two of us (due to your time constraints, and myself prepping for Step 1), chances are that I read the book more recently. Let's let the SDN community decide what is the correct information based on due diligence, shall we?

Case Closed.

 

[alhkim]

p53...Janeway (and Bill Paul's Fundamental Immunology and any other text book) do not always contain the most accurate interpretation of the . I suggest looking for Jacque Banchereau's and Ralph Steinman's review on DCs in Nature for the real explanation for the LC/DC. Steinman "re"discovered the DC in 1973, and Banchereau has been leading the field in their characterization.

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v392/n6673/full/392245a0_fs.html

Botton line: Langerhans cells ARE DCs--they don't become DCs because they are already DCs. True, monocytes are in the bloodstream and differentiate into macrophages upon exiting the bloodstream, but DCs are different. LC mature upon activation, but they are already DCs.

As for the MD/PhD thing, I was just trying to give some credibility to my side of the story. For non-immunologists, they point we are debating is totally irrelevant, since the simple fact the DCs exists is sufficient knowledge for step I. I'm not looking for someone to put me up a on pedestal or expect people to all of a sudden praise me for this. Not sure where in my previous post you think that I was looking for this.

As for your tone of posts, I suggest you just pipe down a tad. You, of course, do not have to do anything, and you probably won't, which is fine. But to say that I do not possess high school logic skills? C'mon now. And for the statement, when we get PhDs we specialize, that is half right. You are still tested on the entire field of immunology in front of a group of faculty through oral exams. Only then you realize how behind textbooks are.

Like I said before...let's not hate here. We are both doing the same thing--making sure the right information is out there so that sites like SDN remain credible.

What part of this did you not understand? I clearly stated that langerhans cells BECOME dendritic cells. For simple minds, they are about the same as a monocyte is to a macrophage. NOW TELL US IF YOU ARE EVER GOING TO SEE A MONOCYTE OUTSIDE THE BLOODSTREAM. Do you follow?

For someone with a poor grasp of BASIC immunology they are the same, for the rest of us that understand the mechanism, there is a reason it is renamed dentitic cell once it is in the lymph node. Obviously, if it isn't in the lymph node a dendritic cell than it is STILL a Langerhans cell. Gee, I wonder if they are the same cell? Anyone with a HIGH SCHOOL logic ability can figure that out.

As for the comment about MD/PhD. You are not going to get anyone to kiss your butt. YOU CAN'T ACHIEVE EXPERT WITNESS STATUS BY BOASTING YOUR TITLE ON SDN. On SDN where anonymity reigns, checks and balances by fellow members overrules a title that Y0U hold in high regard. We don't give a damsel if you are a MD/PhD or a high school dropout, if you post knowledge about something and it is reinforced by the literature than knowledge trumps Title.

Also, we all know when you study for a PhD you specialize. When you specialize it is likely that you tend to forget about the basics. I recommend you reread Janeway Immunology on Cell mediated response and come back with a book report. Let's face it, between the two of us (due to your time constraints, and myself prepping for Step 1), chances are that I read the book more recently (and currently more versed in BASIC immunology than you are). Case Closed.

"The Langerhans cell with the antigen is in the skin (hence the name skin test) migrates to the local lymph node. Once at the lymph node, with an antigen it is considered mature thus is named dendritic cell."

 

[p53]

p53...Janeway (and Bill Paul's Fundamental Immunology and any other text book) do not always contain the most accurate interpretation of the . I suggest looking for Jacque Banchereau's and Ralph Steinman's review on DCs in Nature for the real explanation for the LC/DC. Steinman "re"discovered the DC in 1973, and Banchereau has been leading the field in their characterization.

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v392/n6673/full/392245a0_fs.html

Botton line: Langerhans cells ARE DCs--they don't become DCs because they are already DCs. True, monocytes are in the bloodstream and differentiate into macrophages upon exiting the bloodstream, but DCs are different. LC mature upon activation, but they are already DCs.

As for the MD/PhD thing, I was just trying to give some credibility to my side of the story. For non-immunologists, they point we are debating is totally irrelevant, since the simple fact the DCs exists is sufficient knowledge for step I. I'm not looking for someone to put me up a on pedestal or expect people to all of a sudden praise me for this. Not sure where in my previous post you think that I was looking for this.

As for your tone of posts, I suggest you just pipe down a tad. You, of course, do not have to do anything, and you probably won't, which is fine. But to say that I do not possess high school logic skills? C'mon now. And for the statement, when we get PhDs we specialize, that is half right. You are still tested on the entire field of immunology in front of a group of faculty through oral exams. Only then you realize how behind textbooks are.

Like I said before...let's not hate here. We are both doing the same thing--making sure the right information is out there so that sites like SDN remain credible.

Yeah, let's not hate here. You can have your semantic argument to flex your accomplishment muscle. Good job, on your MD/PhD. It feels good to be acknowledged, huh? You are welcome.

For the rest of the SDNers, if you see an antigen presenting cell in the skin i.e EM or light microscope for Step 1 it is Langerhans Cell. If you see it in the lymph node it is a dendritic cell. You would be an idiot if you pick Langerhans cell in the lymph node over dentritic cell on a Step 1 EM or Light microscope question.

Also, anyone with a high school logic ability would have been able to realize that the reason I corrected Janders is because he neglected to mention that an antigen presenting cell migrated to the lymph node rather than passively stay there and wait for passing lymphocytes. This is the important point that I was referring too.

If you still agree with Jander's assessment of the mechanism of antigen presentation we need to question the program that would give a PhD in immunology to someone that doesn't understand such a fundamental concept. This could just be due to the department having low standards or low expectations of its graduate students. Regardless, it isn't your fault so don't bow you head down.

 

[p53]

funny...i had just assumed that s/he inferred the DC migrated to the LN before presenting the antigen--i originally didn't even think that the poster meant that the DC stayed out in the periphery. when I reread the post, i neglected to see that s/he never specifically mentioned that part....that is totally my bad. I absolutely missed that point. we've been arguing over nothing.

ALTHOUGH...recent data regarding LCs show that most of them do reside in the periphery and do present antigen there, but for the intent of inducing tolerance, rather than activation of immune responses. And LCs (in their immature form) can migrate to LN for induction of peripheral tolerance. There is always a "but" in science and medicine.

p.s. one more thing...if we aren't here to hate, then why even comment about the quality of graduate school, as you did in the last paragraph.

I'm not hating you. I'm hating the graduate school. There is a difference.
Look man, I'm through talking about this. Don't be offended but I am going to ignore any of your posts about immunology from here on out. If you want to talk about anything else I'm game.

 

[alhkim]

funny...i had just assumed that s/he inferred the DC migrated to the LN before presenting the antigen--i originally didn't even think that the poster meant that the DC stayed out in the periphery. when I reread the post, i neglected to see that s/he never specifically mentioned that part....that is totally my bad. I absolutely missed that point. we've been arguing over nothing.

ALTHOUGH...recent data regarding LCs show that most of them do reside in the periphery and do present antigen there, but for the intent of inducing tolerance, rather than activation of immune responses. And LCs (in their immature form) can migrate to LN for induction of peripheral tolerance. There is always a "but" in science and medicine.

p.s. one more thing...if we aren't here to hate, then why even comment about the quality of graduate school, as you did in the last paragraph.

Yeah, let's not hate here. You can have your semantic argument to flex your accomplishment muscle. Good job, on your MD/PhD. It feels good to be acknowledged, huh? You are welcome.

For the rest of the SDNers, if you see an antigen presenting cell in the skin i.e EM or light microscope for Step 1 it is Langerhans Cell. If you see it in the lymph node it is a dendritic cell. You would be an idiot if you pick Langerhans cell in the lymph node over dentritic cell on a Step 1 EM or Light microscope question.

Also, anyone with a high school logic ability would have been able to realize that the reason I corrected Janders is because he neglected to mention that an antigen presenting cell migrated to the lymph node rather than passively stay there and wait for passing lymphocytes. This is the important point that I was referring too.

If you still agree with Jander's assessment of the mechanism of antigen presentation we need to question the program that would give a PhD in immunology to someone that doesn't understand such a fundamental concept. This could just be due to the department having low standards or low expectations of its graduate students. Regardless, it isn't your fault so don't bow you head down.

 

[fang]

funny...i had just assumed that s/he inferred the DC migrated to the LN before presenting the antigen--i originally didn't even think that the poster meant that the DC stayed out in the periphery. when I reread the post, i neglected to see that s/he never specifically mentioned that part....that is totally my bad. I absolutely missed that point. we've been arguing over nothing.

ALTHOUGH...recent data regarding LCs show that most of them do reside in the periphery and do present antigen there, but for the intent of inducing tolerance, rather than activation of immune responses. And LCs (in their immature form) can migrate to LN for induction of peripheral tolerance. There is always a "but" in science and medicine.

p.s. one more thing...if we aren't here to hate, then why even comment about the quality of graduate school, as you did in the last paragraph.

BTW, it's "Langhans" cells in the skin, "Langerhans" cells are the cells that participate in granulomatous inflammation.

 

[alhkim]

Langhans cell: any of the cells of cuboidal epithelium that make up the cytotrophoblast

Langerhans cell: immature dendritic cells containing large granules called Birbeck granules located in the skin

true, langerhans cells are actively participants in the granulomatous inflammation you speak about.

BTW, it's "Langhans" cells in the skin, "Langerhans" cells are the cells that participate in granulomatous inflammation.