ANY truth to the vaccine debate?

[Perth]

It is theoretically possible that original antigenic sin could make a given vaccine bad, if it's some variant of a future, more virulent strain. Under this scenario, the new vaccine may be very ineffective, because of the previous vaccination. However, we cannot know this ex ante. Further, this can go both ways, in that early vaccinations can give somewhat of a lifelong immunity. I heard something happened like this for old people with respect to the recent H1N1 epidemic.

That is an interesting point, but I don't think that I would consider that potential problem to be unique to vaccination since that quirk of the immune system doesn't discriminate between exposure to a wild type pathogen and a vaccine. Vaccination does give us a little more control/influence in that we can continue updating vaccines and we can manage their administration. In contrast, we usually cannot pick which strains of an actively circulating pathogen a person will be initially exposed to and when that exposure will take place.

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[SpecterGT260]

which quirk are we talking about? this doesn't sound right. There is no reason that I am aware of for immunity to one illness to make someone more susceptible to another one.

EDIT: about H1N1 - the issue here is that we did not predict it appropriately. Every year the CDC heads off to the phillipines or something like that and figures out what the next year's strains will be. We get a "flu coctail" shot containing Ag from 3-6 different strains. We missed H1N1. That is all. Sure, it was a little more virulent and had increased pathology - but not overwhelmingly so. We just missed it in our vaccine. The following year had H1N1 in it and it was no big deal.

Are you guys saying that the immune system will be less equipped to handle a later vaccine if it is too close to a former? That is not true by any mechanism I am aware of.

 

[sibitrum]

That is an interesting point, but I don’t think that I would consider that potential problem to be unique to vaccination since that quirk of the immune system doesn’t discriminate between exposure to a wild type pathogen and a vaccine. Vaccination does give us a little more control/influence in that we can continue updating vaccines and we can manage their administration. In contrast, we usually cannot pick which strains of an actively circulating pathogen a person will be initially exposed to and when that exposure will take place.

Right, but with a vaccine, you are guaranteeing exposure to high levels of antigen, whereas in every day life you may or may not encounter it.

Are you guys saying that the immune system will be less equipped to handle a later vaccine if it is too close to a former? That is not true by any mechanism I am aware of.

That's basically the idea. Here's a diagram from wikipedia:

A high affinity memory B cell, specific for Virus A, is preferentially activated by a new strain, Virus A1, to produce antibodies that ineffectively bind to the A1 strain. The presence of these antibodies inhibits activation of a naive B cell that produces more effective antibodies against Virus A1. This effect leads to a diminished immune response against Virus A1, and heightens the potential for serious infection.

In the context of vaccines, the memory B cell might be against an early childhood vaccine, for example, and virus A1 might be one encountered as a young adult, either in vaccine or wildtype form.

 

[SpecterGT260]

I've never heard of Ab inhibiting other BCR activation. There is no reason to. A b cell is not sensitive to a virus. It is sensitive to an epitope. If a virus develops a new epitope or alters it's epitope to one that is no longer recognized by the memory cells, we are just back to square 1. I am an hour out from my immuno final and haven't heard anything about this inhibition.

 

[SpecterGT260]

Can you link the article? I'm having issues w the diagram out of context. We could claim that the original Ab can sequester Ag away from the naive cell, but if an attack occurs we will still get the new b cell activation as Ag levels rise, the original b cell will still hyper mutate to produce Ab of higher affinity, and the presenting cells will still reach secondary lymph tissue to recruit t cells which then recruit b cells with similar specificity.

 

[sibitrum]

I've never heard of Ab inhibiting other BCR activation. There is no reason to. A b cell is not sensitive to a virus. It is sensitive to an epitope. If a virus develops a new epitope or alters it's epitope to one that is no longer recognized by the memory cells, we are just back to square 1. I am an hour out from my immuno final and haven't heard anything about this inhibition.

http://en.wikipedia.org/wiki/Original_antigenic_sin

The idea is that the new virus still has the epitope, or one similar to it, such that the memory cell's antibody has low affinity. Alternatively, the new virus could just have other epitopes in greater abundance, such that the antibody is less likely to encounter the virus and/or cannot coat it with antibody as well. However, the new collection of epitopes is still enough to activate the low-affinity memory B cells.

 

[sibitrum]

The way in which the naive B cells with potentially higher binding affinity are inactivated is that they have Fc receptors that bind to the older effector B cell's antibodies (which remember are lower affinity), which are coating the antigen.

 

[SpecterGT260]

That doesn't make sense. I can't find anything that says b cells have fc receptors. Also, affinity doesn't matter if we are still coating. If they coat, even weakly, we still get fc response from phagocytes and complement function. I could accept a lower degree of coating which would impact response by hiding Ag from naive cells and offering too low of fc signal for effective clearance by APCs. But the rest doesn't seem right.

 

[sibitrum]

That doesn't make sense. I can't find anything that says b cells have fc receptors. Also, affinity doesn't matter if we are still coating. If they coat, even weakly, we still get fc response from phagocytes and complement function. I could accept a lower degree of coating which would impact response by hiding Ag from naive cells and offering too low of fc signal for effective clearance by APCs. But the rest doesn't seem right.

I'm not an expert in the area, and it's still a very new area of research, but I think you are correct to say that it comes down to a matter of degree. To relate it to a separate idea, that's why affinity maturation is so important, because without it, the immune response will be much less robust.

The specific receptor I was referring to is the Fc gamma RIIB1, noted in these articles.
http://www.ncbi.nlm.nih.gov/pubmed/11571279
http://www.ncbi.nlm.nih.gov/pubmed/7797241

 

[SpecterGT260]

Ok, I did find it. I don't think it is a big deal in terms of vaccination. The fc gamma receptor on b cells will in fact inhibit activity. However, vaccinations will more often illicit a t cell response via APCs. t cells are the crux for vaccinations. I don't believe this will be hindered by ineffective Ab in any tangible way

 

[SpecterGT260]

I think it is interesting in theory but less important clinically or epidemiologically

 

[sibitrum]

I think it is interesting in theory but less important clinically or epidemiologically

Fair enough, but like I said earlier, you can't really know how important it is going to be in the future, because you can't predict antigenic drift.

 

[DoctwoB]

Ok, I did find it. I don't think it is a big deal in terms of vaccination. The fc gamma receptor on b cells will in fact inhibit activity. However, vaccinations will more often illicit a t cell response via APCs. t cells are the crux for vaccinations. I don't believe this will be hindered by ineffective Ab in any tangible way

Depends on the vaccine. live virus = mainly T-cell response. Killed virus/purified protein antigen = mainly humoral response w/ T-cell help (class switching, memory, etc.). Purified polysaccharide (e.g. pneumovax, meningicoccus vaccine) = only B-cell response, no T-cell involvement as the TCR only binds peptides.

 

[SpecterGT260]

Depends on the vaccine. live virus = mainly T-cell response. Killed virus/purified protein antigen = mainly humoral response w/ T-cell help (class switching, memory, etc.). Purified polysaccharide (e.g. pneumovax, meningicoccus vaccine) = only B-cell response, no T-cell involvement as the TCR only binds peptides.

T-cell help IS a T-cell response. I was typing it out on an ipad so I decided to conserve verbage. Also, to restrict T-cell resposne to live virus is somewhat missing the point. All vaccine types with the exception of LPS-only will illicit a T response. Think about conjugates for instance. The primary goal is B cell development. But this doesn't happen without Tfh input. We also have toxoids which can very often be peptide, and pathogen subset vaccines which are also often peptide based.

The point is - B-only immunity (T-independent) is quite limited and the majority of what we are doing with vaccines is targeted to both B and T cells. Even live virus vaccines are often given via the mucosa where there is a relative overabundance of naive B cells compared to IM or IV administration. One without the other doesnt happen very often.
(this may be getting convoluted but it is because I am editing a lot.... sorry)
So Live virus: can directly activate CD8 T cells via presentation by infected APCs. Also there will be cell death and phagocytosis an presentation to CD4 cells as well as incidental activation of B cells in lymphoid tissue. I dont think calling this "mainly T cell" is appropriate.

As for purified protein from pathogens - phagocytic APCs will cross present on MHC-I to CD8 cells, so even here we get an incidental B cell response by simply coming into contact with free Ag in the serum. We get a CD4 T cell response by APCs and we also get a CD8 T cell response by cross presentation.


Go to your clinical vignettes: How effective are vaccines in patients with Hyper IgM? What are the typical treatments? Not vaccination, but antibiotics and Ig replacement therapy. This is only due to defective T cell activity

 

[facetguy]

http://www.kiwimagonline.com/2012/0...ety-of-vaccines-the-third-rail-of-pediatrics/

Pediatrician's view on firing patients. I think his approach is a good one.

"Most [parents]—I’d estimate well over 75 percent—decide after our conversations to begin immunizing their children. What would they have done otherwise? Check out of the medical system entirely? That might seem drastic, but I’ve seen this happening more lately. I have seen children who have not been to a pediatrician in years because the parents are afraid they’ll be chastised for their beliefs. Is this what’s best for their children? Talk about throwing the baby out with the bath water."