Newsletter #319: How Sleep Helps Train the Immune System 🦠
It has been known for some time, based on a mountain of observational evidence, that losing sleep makes you more likely to fall ill.
For instance, army recruits who report sleeping less than six hours per night are four times more likely to be diagnosed with a respiratory infection. This has also been borne out in viral challenge trials, wherein volunteers are deliberately exposed to respiratory viruses and then kept in quarantine. In one such study, subjects who were getting less than 7 hours of sleep per night were nearly three times more likely to go on to develop a cold, compared to those who averaged 8 hours.
Poor sleep also compromises the immune response in vaccination. A recent meta-analysis found that insufficient sleep, around the time of vaccination, significantly reduces the antibody response, tantamount to the waning of COVID-19 vaccine antibodies. This would seem to suggest that sleep influences acquired immunity.
But despite these consistent finding, the underlying physiological mechanisms have remained elusive — until very recently.
In a new study, German researchers have started to uncover how sleep helps the immune system learn to recognize pathogens. Importantly, this also sheds light on how other dimensions of sleep, beyond just duration, may be key for optimizing the immune response.
This Week’s Research Highlight
Sleep helps train T cells through hormonal shifts occurring during slumber.
Sleep clearly plays a role in regulation of the adaptive immune system. But how exactly?
One possible clue lies in the patterns of immune cells in the blood. Concentrations of T cells, in particular, do not stay constant. When we are asleep, circulated levels of T cells are reduced.
Now, this might sound counterintuitive, but there’s actually a really good reason for this. In order for T cells to do their job effectively, they need to be trained by being exposed to antigens, and this educational process takes place in the lymph nodes. So, for instance, after you receive a vaccination, naïve T cells migrate over to the lymph nodes, and they subsequently develop into more specialized cells, built to target the antigen presented by the vaccine.
The idea here is that sleep, somehow, promotes redistribution of T cells out of the blood and into other tissues, and in doing so improves the adaptive immune response.
To examine this hypothesis, researchers at Ludwig Maximilian University of Munich recruited 14 healthy young adults, and had them visit the sleep laboratory for two different 24-hour experimental sessions, which were separated by at least a month. Throughout both sessions, blood samples were collected every four hours, to observe changes in circulating immune cells.
In one session, they were permitted to sleep for an 8-hour period, during which time their sleep was objectively measured via polysomnography. Blood samples were collected via a forearm catheter connected to an adjacent room via a long thin tube, which allowed the researchers to take blood without disrupting sleep.
In the other session, participants were kept continuously awake in the lab for the entire 24-hour period. Afterwards, they returned home, got a full night of sleep, and then came back to the lab for a final blood sampling to see if there were any residual effects from the sleep loss.
Blood samples were analyzed for numbers and types of T cells, and the researchers also performed a cellular migration assay so that they could determine where the T cells were headed.
Sure enough, the scientists found that sleep promoted T cell migration toward a specific signaling protein that mediates migration of T cells to the lymph nodes. There was a marked difference in T cell migration potential between the sleeping and waking conditions, and a night of recovery sleep didn't fully abolish this disparity. This suggests that sleep loss may have a sustained impact on the ability of T cells to move to lymphoid tissue and adapt to new antigens.
But the researchers didn't stop there. They wanted to figure out why sleep has this impact on peripheral immune function, and they suspected that endocrine factors were at play.
To test this, they conducted some in vitro studies. First, they exposed T cells to growth hormone and prolactin — two hormones that reliably go up while you're asleep. Both boosted migration of T cells to the key signaling protein mentioned earlier.
Furthermore, they took samples that had been collected during sleep, and which were accordingly high in GH and prolactin, and treated them with antagonists to these hormones. This blunted the migratory propensity of the T cells, verifying that these hormones were indeed responsible.
So, there are a couple of other interesting takeaways here, aside from revealing the mechanisms linking sleep to immune function.
One aspect of T cell behavior, that sounds sort of confusing at first, is they follow a strong circadian pattern wherein they naturally rise in the blood at night. That may appear to contradict what I’ve been saying so far, but this is where sleep, and the hormonal shifts associated with it, enter the picture. Sleep overcomes this tendency, driving the movement of T cells out of circulation and toward lymph nodes.
So, this seems to indicate that nighttime is a critical period for the control of the fate of T cells.
From a practical standpoint, this might mean that it's not just a matter of how much you sleep, but when you sleep. For instance, shift work could disrupt the immune system independent of the amount of sleep that you achieve, and indeed we know that night shift work is linked to greater susceptibility to infections.
Additionally, this finding could explain, in part, the weaker responsiveness of the adaptive immune system in older people. We've known for a long time, for instance, that older adults have impaired immune responses to vaccines. It is probably no coincidence that the elderly also struggle to attain quality sleep. You see, growth hormone secretion is highest during slow wave sleep, and slow wave sleep plummets as people get older. This shift in sleep architecture is accompanied by a dramatic (-75%) decrease in growth hormone during sleep.
Taken together, this suggests that not just duration, but also the timing and quality of sleep, could play a key role in the ability of the immune system to build specific defenses to pathogens, as well as other harmful substances.
Random Trivia & Weird News
Some birds can fly for up to 10 consecutive months without touching the ground.
The common swift is exquisitely adapted to life in the air.
Researchers have attached micro-data loggers to swifts, and have found that they are able to spend months at a time in flight.
And yes, this means that they sleep while airborne, making them very impressive multitaskers.
Podcasts We Loved This Week
- Joel Jamieson: Heart rate variability: how to measure, interpret, and utilize HRV for training and health optimization. Via The Peter Attia Drive.
- Gül Dölen: Can psychedelics improve mental health? Via The Joy of Why.
Products We Like
Nature Made Melatonin Gummies
Supplemental melatonin is fantastic for helping realign your circadian rhythm when it has gone astray. But it’s important to source melatonin carefully, because quality control for over-the-counter supplements can be really questionable.
In one study, researchers systematically analyzed the actual melatonin content in 31 supplements purchased from groceries and pharmacies, and they found that melatonin content varied from −83% to +478% of labeled melatonin, and 70% had a melatonin concentration that was ≤ 10% of what was claimed!
That’s why you want to make sure to get a supplement that is independently lab-tested, like Nature Made. As an added bonus, this brand is super easy to find in stores.
humanOS Catalog Feature of the Week
Body Timing and Health
In this course, Dan goes over the evolution and physiological purpose of biological rhythms, as well as how they are regulated in response to environmental stimuli. Then, he delves into how these biological clocks influence both acute performance and long-term health, and what happens when they get out of sync.
Finally, all of this juicy info is synthesized into practical applications — what you can do right now to align your circadian rhythms, to keep your mind and body working at their very best.
Wishing you the best,
