Comments on: Why a vaccine failed, and maybe a fix

By: iayork

iayork — Fri, 16 Jan 2009 22:14:00 +0000

Th2 responses can be elicited to OVA in the presence of alum adjuvant, which is a strong immune stimulator. I'd call alum a moderate immune stimulator, not a particularly strong one. also (and maybe relevant to the RSV paper comment on TLR stimulation) alum doesn't work through TLRs per se (see here, for example).

By: Peer

Peer — Fri, 16 Jan 2009 22:01:45 +0000

Th2 responses can be elicited to OVA in the presence of alum adjuvant, which is a strong immune stimulator. At least the initial sensitization response is CD8+ T cell and IFN-y dependent (so I guess a Th1 response, if the paradigm of Th1/Th2 is trustworthy), but after the challenge (with OVA+alum), the immune response after a sensitization (with OVA protein alone) is Th2.

Maybe this is similar to the vaccination case, where the initial response with RSV was enough to elicit an immune response but subsequent (“suboptimal”) exposures to the virus antigens resulted in a Th2 response.

But then I wonder how the localization of vaccination and the location of subsequent exposure to the virus play a role.

By: iayork

iayork — Fri, 16 Jan 2009 19:37:41 +0000

A crude rule of thumb (in other words, the rule I teach to the undergrads) is that with strong innate immune stimulation you get TH1 responses, without innate stimulation you get TH2. The concept is that parasitic worms tend to be pretty good at hiding, which means they don’t induce strong innate immune stimulation; so immune responses with only weak innate stimulation (throughout evolutionary history, anyway) are more likely to be from parasitic worms, and TH2 responses are more appropriate. Of course that’s only an approximation, but you can see how it fits with the RSV story here.

By: Peer

Peer — Fri, 16 Jan 2009 19:31:17 +0000

I think this is very interesting. Is the magnitude of stimulation of APC (DC, MAC, B cell) related to what type of immunity (Th1/2) is elicited? So that the presence of foreign peptide (even something abstract like moth cytochrome) can result in increasing order or PAMP (whether it is TLR, RIG or other cytosolic, or P2X/Y) stimulation in 1. tolerance, 2. Th2, 3. Th1 immune responses?

By: John Kelsey

John Kelsey — Thu, 15 Jan 2009 21:47:29 +0000

Thanks! That makes sense. Is the TH1 response the one that generally works for stuff that invades the cells, and TH2 for stuff that stays outside the cells? That’s how it looked from what I read, but I clearly didn’t get the whole detail of the TH1/TH2 distinction before….

By: iayork

iayork — Wed, 14 Jan 2009 20:55:08 +0000

You still get an antibody response in TH1 responses, though it tends to be different classes (isotypes) of antibody.

It’s hard to make general statements in virology, but antibodies are often important in immunity to viruses. Antibodies are very commonly critical in protection against viruses — that is, in preventing a second infection (or a first infection if you’re vaccinated) — which is one reason so many killed virus vaccines are so effective. In some cases, antibodies are also important in clearing ongoing virus infections.

By: John Kelsey

John Kelsey — Wed, 14 Jan 2009 20:32:45 +0000

Do you still get a big antibody response when your body goes down the Th1 response path? I thought going down the Th1 path basically meant that you wouldn’t produce a lot of antibodies. (Don’t the beta cells need the Th2 helper T-cells to interact with them and give them the signal to start cranking out antibodies? Can Th1 cells do that, too?)

Are antibodies important in your immune response to viruses? I thought they were. (Don’t they measure antibody levels in blood to see whether some old vaccine is still protecting people against infection?) Or do you still produce antibodies when you go down the Th1 path, but just different classes?