Original Antigenic Sin (Sounds ominous, doesn’t it?)

One part of immunology goes a little bit like this:

1. You get exposed to a bacteria or virus.

2. Specialized cells called macrophages (or neutrophils) gobble up the bacteria or virus (or fungus or whatever), and digests it with some enzymes and other chemicals.

3. The macrophage then presents the bits and pieces of the virus or bacteria it just ate. To whom? They present it to B lymphocytes and T lymphocytes.

4. B lymphocytes take the bits and pieces, also called antigens, and create specific antibodies against it.

5. The antibodies attach to circulating viruses and bacteria, inactivating them and marking them for destruction by the T lymphocytes and additional macrophages.

6. If you survive this first encounter, the B lymphocytes go dormant, waiting for the next time you’re infected.

7. If you get infected again, the B lymphocytes are pressed into action again, but they produce the antibodies to which they are already coded, and they do so furiously. New B lymphocytes go back to step 4.

Of course, this is the “quick and dirty” description of what happens inside of us when we are exposed to viruses and bacteria that cause disease. The actual process is much longer and complex, too long and complex to explain here. But you get the point. You’re exposed, you make antibodies, and, if you’re exposed ever again, you respond quickly and vigorously, preventing the new infection from gaining a foothold and making you sick.

This is the reason why some diseases like chickenpox usually only attack us once. The “memory” of the dormant-then-activated B lymphocytes lasts long, and the chickenpox virus is antigenically similar from one wave of infections to the next. That is, the antigens don’t change in shape, and the antibodies can attach to the new infection as easily as they did when they first defended you.

There are some exceptions to this reaction, also called an “anamnestic response”. There are times when the interval from one infection to another is too long, and the dormant B lymphocytes end up dying and are unavailable to defend you when the second infection occurs. There are also times when you have an underlying medical condition that prevents those B lymphocytes from responding. Or, if they do respond, the other cells cannot come along for the ride and help in the defense of your body.

The best way to keep your body always primed and ready would be to be continuously exposed to the disease. And that was the case when chickenpox and measles were around, killing people. You’d be exposed over and over since you were very likely to come into contact with a person who had them when you were a kid, when you had your kids, when your kids had kids, or if you were a person who had a new batch of snot-nosed  kids to deal with every so often – like a teacher.

One thing that vaccines did very well was to make cases of things like chickenpox dwindle and almost disappear. Instead of getting the infection and the high chance of bad outcomes from it (e.g. encephalitis, skin infections, or pneumonia), you just got a shot full of antigens – the bits and pieces of the virus – and your immune system would be primed and ready, sans actual disease. However, instead of being re-exposed from time to time, you no longer are exposed. If your B lymphocytes die off, then you’re not immune to the disease anymore. This is why we need boosters.

We also need boosters because, although we’ve tried and tried hard, there are still plenty of cases of chickenpox, measles, whooping cough, and other vaccine-preventable diseases. Are they around because other animal species can also get them and so “hide” in their natural host until they hit humans again? Not really. Humans are the only natural reservoir for many of these diseases, especially chickenpox and measles. (Yes, there are other diseases out there that hit animals and are related to human diseases, but they’re not exactly the same.)

Boosters work, and they work well.

However, vaccines don’t work as well with viruses whose antigens change quickly, or whose natural reservoir is not humanity. This is the case with influenza viruses. Type A and B viruses can infect humans, pigs, birds, horses, dogs, and even some seals. So we can get rid of the viruses from humans, but they’ll just go hang out with pigs until a non-immune person gets exposed to them. Also, influenza viruses change their antigens almost yearly. To our immune system, this year’s flu is not caused by last year’s flu. Our dormant B cells can throw off antibodies, but those antibodies are not adept to neutralizing this year’s flu if they were created against the flu from years ago.

Or is it?

During the 2009 flu pandemic, there was an interesting phenomenon occurring in the populations that were infected. Children were making plenty of antibodies against the new flu virus. Older adults were making plenty of antibodies against the new flu virus. But young adults and adults were not making these antibodies. What the heck, right? We’ll get back to that observation in a second.

An epidemiologist made an interesting observation about the immune system some years ago. He noticed that people exposed to a flu virus (say it is “flu X”) would make really good antibodies against that flu X. If they were exposed to flu Y, however, they would make a lot of antibodies against flu X, but very little against Y. When he took into account these people’s age, he noticed that they belonged to a subset of people that had not seen an epidemic of flu X ever, but were old enough to have seen flu W, M, or flu N at some time. On the other hand, people who had seen flu X when they were very young or had not seen any flu of any kind, well, those people made plenty of good antibody against flu Y.

This epidemiologist called this observation the “Original Antigenic Sin” theory. He theorized that people who had seen other flus would make antibodies only against the flu they had originally encountered when they were children. Their antibodies were being made by the dormant B lymphocytes that were called to action after the new infection. These people were young adults and adults, and they didn’t do well with new flu viruses because that reaction from old, dormant B lymphocytes was vigorous enough to trick other B lymphocytes into thinking that enough was being done. However, the reaction was not specific enough to deal with the new flu.

On the other hand, children who had not seen the flu before made a vigorous and specific response to the new flu because they had no old B lymphocytes to take over. Older adults also had a good antibody response to a new flu because their old and dormant B lymphocytes had died out. To them, the infection was new, immunologically speaking. Here, I made a table to explain it better:

Immune response is not indicative of disease outcome, by the way.

During the 2009 pandemic, epidemiologists saw that older adults were not getting sick as much – or as severely – as younger adults. One of the things that explained this was this concept of original antigenic sin. Another thing that explains it is that older adults are more likely to be consecutively vaccinated for quite some time because they’ve been placed on the recommendation list. One other thing that could explain this was that these older adults had been exposed to the same H1N1 virus many years prior and had some sort of “lifelong” immunity against it.

Remember, during the pandemic, children were affected just as bad as young adults, throwing the original sin theory out the window. They made a lot of antibodies, but this wasn’t a sign that they fared any better.

It was that last point that didn’t make much sense. Yes, the 2009 H1N1 virus is similar to previous H1N1s seen in history, but, from an antigenic point of view, it was new. It was novel. And that novelty is the only thing that explains why it went around the world so quickly. Unfortunately, many in the media, in public policy, and – why else would I be well into 1,300 words of this post? – anti-vaccine people, believe that grandma and grandpa Smith, at the age of 70+, have an immune system that remembers a virus from decades ago.

And it’s that last point that anti-vaccine people have been harking for a while now, and especially in light of the current 2012-13 H3N2 flu season that has been so heavy. They claim that children should be exposed now to this potentially deadly flu in order to get “lifelong” immunity, and they use that observation from the 2009 pandemic as an explanation. When presented with the possibility that older adults fared better because of consecutive immunization, they scamper away or present some bogus explanation. When presented with the evidence that children didn’t do so well in 2009, they also counter with poor science and really no good evidence.

In essence, the anti-vaccine crowd would very much like to have kids exposed to a potentially deadly pathogen instead of being vaccinated because, in their minds, it will lead to lifelong immunity and none of the “dangers” of vaccines. They do this for measles, for chickenpox, for whooping cough, and now for flu. They ignore all the families who have been severely affected by influenza, some whose children have died and others who have been left with severe consequences of their infection. Worse, with regards to the flu, they ignore that the flu mutates very fast and has other animals as reservoirs, making our immune system susceptible to it every year, almost like clockwork.

Of course, almost like clockwork, anti-vaccine people will say that we all survived past pandemics and epidemics, so the flu isn’t deadly. This is almost like saying that we all survived World War II, so that war wasn’t deadly. That is, they have very different definition of deadly. And you can tell that they do because they say a vaccine is deadly while things like polio, measles, and flu are not. All the evidence says they are deadly. Very deadly.

So, now that you have this information, you’ll be able to counter the argument that an exposure to flu now is a guarantee to immunity later. Tell them that it doesn’t work that way with flu because it mutates fast. When they bring up what happened in 2009, tell them about the original antigenic sin and how they’re misinterpreting it. Then, when they bring up someone who didn’t die from the flu, bring up someone who has… And then ask for someone who has died from vaccines.

If you fill up a stadium with the number of people who have died from flu, you’d only need to fill a seat or two to represent the number of people who have directly died from a flu vaccine. Again, anti-vaccine people are not good gamblers.