The data to date suggest that the current H1N1 strain is infecting individuals 17 and younger at a disproportionate rate.  While still unclear that this pattern will hold, we may be seeing a curious reflection of our collective immunological memory playing out.

To understand this pattern, we need to keep in mind the fact that all battles between our immune system and any invader — virus, bacteria, or foreign protein — play out in three dimensions.  Immune response is all about recognizing shapes that do not belong (”non-self”), and about mounting a concerted response to these alien shapes.  But that response takes time, and is usually most effective when the immune system re-encounters an alien shape it has seen at least once before (this, incidentally, is the logic behind immunizations).

HA and NA

A cartoon model of the influenza virus, showing the two important surface proteins: HA and NA

Influenza viruses, in turn, exploit aspects of our immune response to evade it.  First, they evolve in response to immune pressure by constantly changing the shape of their surface proteins, hemagglutinin (HA) and neuraminidase (NA), the only parts of the influenza virus our immune system “sees”. This enormously successful evolutionary strategy is made possible by the particularly sloppy copying of the viral genome that goes on every time the virus replicates. When you are a virus being hunted down by the immune system, sloppiness works.  Our immune system is thus always playing catch-up, reacting to the shifting shape of the invader.

But what the immune system appears to lack in foresight, it more than makes up for with memory.  In effect, our immune system remembers every shape it has ever encountered and responded to.  Like the grizzled sheriff in an old Western, our immune system can hold a grudge for a long time, and the second response will be swifter and deadlier than the first.  And now, a subtle wrinkle: the immune system can recognize and respond to shapes with great precision, but it is also capable of reacting, albeit less vigorously, to shapes similar to those it has seen before.

Hemagluttinin, one of the surface proteins of the influenza virus

Hemagglutinin, one of the surface proteins of the influenza virus

Our immune system’s ability to patrol for specific shapes, but also to keep an eye out for the shape neighborhood surrounding a specific shape, may help explain the pattern of infection we are seeing with the current H1N1 shape.  While this strain, is, as we mentioned in an earlier posting, entirely new, there have been other H1N1 outbreaks before.  The most recent noteworthy outbreak of H1N1 occurred in 1976, and prompted a massive vaccination program in the US, where more than 40 million individuals were vaccinated (and where the morbidity and mortality due to the side effects of vaccination — particularly a rise in Guillain-Barré syndrome– exceeded the effects of the influenza outbreak).  That H1N1 strain, and others related to it, likely remained in circulation for several years after the 1976 episode.  As a result, individuals that are 33 years old or older have likely been exposed to a version of H1N1, either through vaccination or through contact with the virus itself.  The collective immunological memory of middle-aged and older individuals may be conferring a protective effect on these demographic cohorts.  In contrast, younger individuals, whose immune systems have never seen the current H1N1 or any previous version of H1N1, may be more susceptible to infection, accounting at least in part for the strange demographic character of the current outbreak.

This argument, of course, is at this point only a hypothesis.  Among other things, it relies on the conjecture that individuals exposed to H1N1 in the 1970’s can in fact mount a more effective and swift immune response than that of immunologically naive younger individuals.  This, in turn, depends on the similarity in the surface proteins of the 1970’s H1N1 strains and those of the current strain.  We will know more about this in the days to come.