Tag Archives: Trained immunity

Is a little infection good for you? If so what about radiation?

Could a little infection be good for you?  Well how about the immune stimulation it produces?  We’re talking about trained immunity here, and evidence for it started nearly 100 years ago in northern Sweden.  TB was a much bigger problem back then (Hell, my grandmother died of undiagnosed tuberculosis in a university hospital in 1967).  Bacille Calmette Guerin (BCG) is an attenuated form of mycobacterium tuberculosis (TB to you). Immunizing with BCG was thought to be protective against TB.  100 years later people are still arguing about it.

What no one is arguing about is the fact the unvaccinated infants had a 10% mortality in the first year of life (the good old days weren’t that good), while the vaccinated ones had a 3% one year mortality.  The 10% that did die, didn’t die of TB either.

It’s pretty technical, but basically BCG vaccination jazzes up the immune system, making it more responsive to the zillions of critters infesting us. [ Proc. Natl. Acad. Sci. vol. 109 pp. 17537 – 17542 ’12 ] has the details  — inferferon gamma, monocyte derived cytokines, the NOD2 receptor, histone 3 lysine 4 trimethylation etc. etc.

These are rather nonspecific features of innate immunity, and not specifically directed at anything in particular (which is why it is called trained immunity).

Well infection jazzes up the immune system too.  Cell vol, 175 pp. 1634 – 1650 ’18 showed that white cells of mice found in the lungs (alveolar macrophages) developed it after a viral infection, making them more resistant to a subsequent bacterial infection.  Could this be general?

Which brings us to a much larger fish to fry –hormesis.

Toxicology basically had two models of how we deal with toxic agents

l. Threshold model — below a certain dose, no harm results.  Arguably true — can one molecule of anything kill you?  Used by the EPA for nonCarcinogens

2. Linear no-threshold model — now matter how lot the dose, damage is seen. This is obviously crazy (see #1 above) but apparently is used by the EPA for carcinogens.

Enter model #3 — Hormesis

The best example is the famous J curve for alcohol in which small amounts are beneficial  at low doses for the heart and huge amounts are horrible (although a recent meta-analysis has challenged this  [ Lancet vol. 392 pp. 1015 – 1035 ’18 ], but I don’t trust them — for why see http://science.sciencemag.org/content/sci/361/6408/1184.full.pdf.

Hormesis says that other toxic agents (radiation, cadmium, dioxin, saccharin, polychlorinated biphenyls) all have J curves like alcohol.   Articles explaining hormesis can be found in — Nature vol. 421 pp. 691 -692 2003, Scientific American 9/2003.  The reaction to it — Science vol,. 302 pp. 376 – 379, 2003.

So the moral might be don’t be an immunological or a toxicological snowflake — that which doesn’t kill you makes you stronger.