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How your body clock drives your immune system

The body's internal clock affects the immune system in ways scientists in the burgeoning field of #circadian #immunology are beginning to unwind.

Why it matters: Leveraging the circadian clock's effects on the immune system could help to improve the effectiveness of some treatments for a range of diseases and conditions, a new book and scientific review suggest.

How it works: The body's central clock, or suprachiasmatic nucleus (SCN), is a collection of about 20,000 neurons in the brain that receives signals from the eye when it detects light or other environmental cues from the body.

  • The signals trigger the clock's components — a network of genes that regulate the production of different proteins in the neurons. (Other cells in the SCN also tamp down the neurons' activity). The amounts of those proteins in the cell oscillate over 24 hours, setting the clock's pace.

  • The central timekeeper then coordinates other clocks in the body and sets the rhythm for regulating body temperature, sleep schedule, the release of hormones and a slew of other biological processes.

  • "Without this precise regulation by an internal clock, our entire biology would be in chaos," writes Russell Foster, a professor of circadian neuroscience at the University of Oxford, in his new book, "Life Time" about the science of the body clock and its connection to health.

The immune system is also under the control of the clock: The functions of different immune cells have been found to oscillate over the course of a day.

  • The circadian clock "synchronizes the whole body to the outside world but we don’t know exactly how an immune cell sees it," says Christoph Scheiermann, an immunologist at the University of Geneva and a co-author of a recent review about the circadian immune system.

What's new: Studies suggest the time of day that a vaccine is given can change the immune system's response to it.

  • The immune response to vaccination against influenza or tuberculosis in two different studies tended to be greater in people vaccinated in the morning compared to those who received shots later in the day.

  • Two other small studies found the immune response to COVID-19 vaccination depended on the time of day — but the optimal timing depended on which vaccine was administered.

  • Earlier work found the timing of when medications or treatments for some cancers, asthma, heartburn and other conditions are given can influence their effectiveness.

But, but, but ... The variations between someone's immune system and their body's rhythms mean the best time for a treatment could vary from one person to the next.

  • The rhythms are generally the same for most individuals and its likely recommendations can be made for most of the population most of the time, says Jacqueline Kimmey, a professor of microbiology at UC Santa Cruz.

  • But making recommendations for individuals isn't possible "until we have better ways of measuring what 'time' someone’s body says it is, and more specific knowledge on what 'time' we should be doing something," she says.

  • There can be differences due to genetics, behavior and environment. "Morning" in the body of a night shift worker may be 3pm so if they go for a vaccine at 8am, they may not benefit from the effects of time, says John Hogenesch, a professor of human genetics and director of Center for Circadian Medicine at Cincinnati Children’s Hospital Medical Center.

  • Altering the time may also not be practical for certain therapies like cancer treatments that hospitals have a limited capacity to administer at particular times.

The big picture: Scientists have known about immune rhythms for decades but new tools are allowing them to better understand the cues and components of the body's clocks.

  • Immune rhythms coordinate and balance the immune system's different responses over the course of the day.

  • Parts of the adaptive immune system — which learns to target pathogens through vaccination or infection — are throttled against new invaders during the day.

  • At other times, the responses are turned down so the immune system doesn't turn on itself and trigger an autoimmune disease.

The innate immune system, a more immediate and blanket response to pathogens is also controlled by the clock.

  • In a study published last week, researchers found when mice and marmosets rested, skin cells produced proteins that protected the animals from staph infection and jumpstarted the innate immune response.

The impact: Sleep disruptions can alter the body's clock and throw off the immune defense system, making it more susceptible to disease.

  • It can also push the body to produce stress hormones, which suppress the immune system.

  • Some viruses, like influenza, also disrupt the immune system's circadian rhythm, blunting the immune response and enhancing the virus' own replication.

  • The malaria parasite reproduces in sync with the circadian clock and releases a flood of parasites that overwhelms the immune system at night when its guard isn't as high, Foster writes.

When people are being infected or treated is "a huge variable we're not paying attention to," Kimmey says.

  • Knowing that the adaptive immune system is not as turned up at night compared to the day, employers can take measures to better protect shift workers — like providing protective equipment for frontline medical workers caring for people with a virus, Foster says.

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