Copepod
Copepod

I’ve been fascinated by recent findings on evolution of immune systems. On the one hand, the roots of the classic vertebrate adaptive immune system have been pushed back further back in time (e.g. the identification of RAG in sea urchins); and on the other, invertebrate immune systems are looking much more complex than previously thought, through a completely separate path.

Traditionally, immunological memory has been considered to be a hallmark of the vertebrate immune system. “Memory” here means the ability to respond to a second pathogen exposure in a more rapid and more aggressive manner than on the first exposure. The example we’re all familiar with is vaccination; if your first exposure to, say, smallpox or measles antigen is via a relatively harmless form, then when you are exposed to the harmful, fully-virulent pathogen you develop a very rapid, if not instantaneous, immune response and you are protected from disease. Invertebrates are not, traditionally, believed to have this memory response.

Still, a half-dozen papers over the last five years have claimed to show immunologic memory in invertebrates. I think this started with a 2003 paper on viral infection in copepods,1 but there are also several examples in insects.2 I honestly haven’t examined these papers all that closely, leaving them on the long “Cool papers I will look at carefully when I have time” list. A typical conclusion is:

This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.3

DrosophilaA paper that just came out in BioEssays4 raises a cautionary note on these conclusions — though I’m not very comfortable with at least part of the message. They argue that all the observations that have been interpreted as evidence for immunological memory could just as plausibly have non-immunological explanations: Because the papers only measure end-points (like survival or reproductive success), they risk missing other explanations:

The failure to make assessment of immunological parameters is a consistent weakness in most papers purporting to demonstrate priming, memory or adaptivity in the invertebrate innate immune system.

They also observe that these recent claims fly5 in the face of a great deal of previous research:

The idea that invertebrates have a primitive form of adaptive immune is not new and was explored extensively from the 1960s onwards. … Despite the prevailing zeitgeist of that time, phenomenological observations and experimental analyses failed to produce consistent and convincing evidence for immune memory or specificity.

Both of those points make sense to me.6 The argument I’m not comfortable with is this one:

We argue that the case for adaptive immunity in invertebrates based only on such phenomena is weak and flawed, as it can only be upheld if supported by descriptions of the underlying mechanisms. (My emphasis. IY)

It’s an argument I’m somewhat sympathetic with. Science should be built on understanding, not description — that’s why “phenomenology” is an insult. On the other hand, one needs observations to build hypotheses; otherwise, where do you start? All we know today of vertebrate immunity is built on observations that were, at one point, simply phenomena without an understood mechanism. (To be fair, that line is from the abstract, and in the body of the paper they basically say the same thing as me: “We fully acknowledge that phenomenological investigations are a logical starting point.“)

As I say, I haven’t looked closely at the papers they’re criticizing, and I’m not very familiar with the older literature they mention on invertebrate immunity; but from what I have seen, Hauton and Smith are making reasonable points. My bias is that I want invertebrates to have some form of adaptive immunity just for the cool factor — but I am certainly much more skeptical than I was before reading this.


  1. Kurtz, J., and Franz, K. (2003). Innate defence: evidence for memory in invertebrate immunity. Nature 425, 37-38. []
  2. For example, Pham, L. N., Dionne, M. S., Shirasu-Hiza, M., and Schneider, D. S. (2007). A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathog 3, e26. []
  3. Pham, L. N., Dionne, M. S., Shirasu-Hiza, M., and Schneider, D. S. (2007). A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathog 3, e26. []
  4. Hauton, C., and Smith, V. J. (2007). Adaptive immunity in invertebrates: A straw house without a mechanistic foundation. Bioessays 29, 1138-1146. []
  5. Har![]
  6. At least, in principle — I haven’t read through all the literature closely enough to be confident they’re completely right[]