TH1/TH2 immuno question?

[drmedstudent]

I was a bit confused about how TH0 differentiates into TH1 in presence of intracellular pathogens, and TH2 in presence of extracellular pathogens.
Doesnt the fact that TH0 is being activated by APC displaying MHC Class II itself mean that there's an extracellular (exogenous) pathogen present? So why the heck would TH1 be present....shouldnt eveything be TH2?

If there was ever an ENDOGENOUS intracellular pathogen, that would stimulate MHC Class I and thus CD8 cells.....so how would CD4 TH1 ever get stimulated [CD4 is stimulated by EXOGENOUS pathogens]?

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[HTxFrog]

so Th1 is good for killing stuff like TB for example that gets eaten by macrophages (and B cells) but then not killed. So the macros (and B cells) eat the TB, secrete IL-12, and present the stuff to the Th cells on MHC II (and they express B7 costimulatory ligand thingy too). That causes them to become Th1 cells, then the Th1 cells shoot some IFN-gamma back at the macrophages and activate them to kill the TB and the IL-12-IFN-gamma axis is complete. Does that explain it at all or was that just more confusing?

As for endogenous vs. exogenous I think the wording is just messing you up. If you think about it as extracellular bacteria vs. intracellular bacteria that works better for Th1 vs. Th2. An endogenous antigen getting presented by MHC I to a CD8 cell would be something like a virally encoded protein or a viral fragment or something. Basically there are two different things to think about. MHCI vs. MHCII is just for CD4+ Th vs CD8+ Tc. Antigen presentation to helper T's is always MHCII its more dependent on interleukins which way it goes as far as Th1/Th2

 

[MilkmanAl]

I believe there's a question in UWSA1 that explains this exact phenomenon very well. I suck terribly at immuno, but it made sense to me. Of course, the above description is nice and concise.

 

[drmedstudent]

so Th1 is good for killing stuff like TB for example that gets eaten by macrophages (and B cells) but then not killed. So the macros (and B cells) eat the TB, secrete IL-12, and present the stuff to the Th cells on MHC II (and they express B7 costimulatory ligand thingy too). That causes them to become Th1 cells, then the Th1 cells shoot some IFN-gamma back at the macrophages and activate them to kill the TB and the IL-12-IFN-gamma axis is complete. Does that explain it at all or was that just more confusing?

As for endogenous vs. exogenous I think the wording is just messing you up. If you think about it as extracellular bacteria vs. intracellular bacteria that works better for Th1 vs. Th2. An endogenous antigen getting presented by MHC I to a CD8 cell would be something like a virally encoded protein or a viral fragment or something. Basically there are two different things to think about. MHCI vs. MHCII is just for CD4+ Th vs CD8+ Tc. Antigen presentation to helper T's is always MHCII its more dependent on interleukins which way it goes as far as Th1/Th2

in ur first paragraph, u said TB antigens get presented via MHC II to TH1....but since TB is endogenous, wouldnt it get presented via MHC class I to CD8 T cells?

 

[HTxFrog]

TB is not an endogenous antigen. Endogenous basically means stuff made within the cell. A viral protein is the classic example of an endogenous antigen. Viral DNA/RNA codes for proteins that are not normally found inside the cell. These non-self proteins are presented with MHC class I by any nucleated cells that are infected. They are then recognized by CD8 Tc cells which induce apoptosis.
Exogenous means stuff made outside the cell. This includes all the bad stuff phagocytosed by APCs. These phagocytosed things are then presented w/ MHC class II to Th cells.
Once you are that far, then you can think about Th1 vs Th2. MHC class has nothing to do with that b/c Th cells only recognize antigen presented with MHC class II. At that point different interleukins (ex. IL-12 secreted by macropages -> Th1) determine whether Th1 or Th2 will be favored.