Exam stress slowed students’ vaccine response, and long-running stress weighs on immunity most

Key takeaways

• In a 1992 study of 48 medical students given hepatitis B shots on exam days, the quarter who made antibodies after the first dose had reported less stress and anxiety than their classmates¹.
• A 2004 analysis of 293 studies found that stress lasting minutes revs up some fast-acting defenses, while stress lasting months, such as dementia caregiving or unemployment, was linked to drops in nearly every measure of immune function⁴.
• On space missions, 53% of shuttle astronauts and 61% of space station crew members shed at least one dormant herpes virus, mostly without symptoms, amid the many strains of spaceflight⁵.
• In a 2007 trial of 112 older adults, 16 weeks of tai chi raised T-cell immunity to the shingles virus by 24%, versus 13% (possibly chance) in a comparison group, though shingles cases weren’t counted⁶.
• If stress interferes with daily life, talk with a professional, and if you’re in crisis or thinking about harming yourself, call or text 988¹³¹⁵.

In a study published in 1992, 48 second-year medical students got a hepatitis B vaccine at an unusual moment. Each of their three shots came on the last day of a three-day block of exams¹.

The timing was the point. Researchers wanted to see whether exam stress would change how well the students’ bodies learned from the vaccine¹².

After the first shot, only a quarter of the students made measurable antibodies. Those early responders had reported less stress and anxiety than the rest¹. By the third shot, students who said they had more social support were mounting stronger immune responses¹.

The study came from the Ohio State University lab of virologist Ronald Glaser, who worked for decades with his wife and research partner, Janice Kiecolt-Glaser, on how everyday strain reaches the immune system². Their field, psychoneuroimmunology, has since mapped which kinds of stress matter and how.

If you’ve always believed mind and body work as one system, this research offers support and a few surprises. This article covers what’s well established, which calming practices have measured immune effects, and where the evidence runs out.

Stress lasting minutes revs defenses up, and stress lasting months wears them down

In 2004, psychologists Suzanne Segerstrom of the University of Kentucky and Gregory Miller of the University of British Columbia pooled 293 studies of 18,941 people, published from 1960 to 2001⁴. They sorted stress by how long it lasts.

Minutes. During lab stressors such as public speaking or mental math, natural killer cells, front-line cells that attack infected cells, poured into the blood⁴. The authors read this as the body getting ready for possible injury and infection⁴.

Days. Real-world challenges such as exams produced a subtler shift. Signals that direct cell-based defenses dipped, while signals tied to antibody responses rose. Natural killer cell activity and T-cell growth in lab tests declined, more so in older people⁴.

Loss and disaster. Sequences of events such as bereavement or a natural disaster mostly showed no reliable immune change. Losing a spouse was linked to lower natural killer cell activity⁴.

Months or years. Chronic stressors with no clear end, such as caring for a spouse with dementia, living with a disability or being unemployed, were linked to declines in nearly every functional immune measure⁴. That included antibody responses to flu vaccine⁴. Older people and people who were already ill showed more stress-related immune change⁴.

One surprise: how stressed people said they felt generally didn’t match their immune changes⁴. The kind and length of the stressor mattered more than a score on a questionnaire.

Hormones carry the message. Stress switches on the nervous system’s fight-or-flight branch and the hormone chain that ends in cortisol, and those hormones change which signaling proteins immune cells release³. In lab studies, beta blockers, drugs that blunt adrenaline’s effects, eased some stress-related immune changes³.

Our mind-body article explains how long-term stress can make immune cells stop listening to cortisol’s calming signal. A later article in this series covers cortisol itself.

Under stress, the immune system can lose its grip on dormant viruses

Some viruses never leave. After chickenpox, mononucleosis or a first cold sore, herpes-family viruses such as varicella zoster, Epstein-Barr and herpes simplex stay in the body, kept quiet by cell-based immune defenses⁵.

Stress can loosen that grip. In a 1999 review, Glaser and colleagues noted evidence that stress improves Epstein-Barr virus reactivation in people³. In the 2004 analysis, antibodies against Epstein-Barr rose after exams⁴. Rising antibodies may mean the virus is stirring, the authors noted, though they could also reflect a busier antibody system⁴.

The most dramatic evidence comes from space. NASA scientists tested saliva and urine from 112 astronauts before, during and after flights⁵. At least one herpes virus turned up in 47 of 89 shuttle astronauts (53%) and 14 of 23 space station crew members (61%)⁵.

Shedding of Epstein-Barr, chickenpox-shingles virus and cytomegalovirus was more common during flight than before or after it, or in healthy people on the ground⁵. Cortisol in saliva ran higher before and during flights⁵.

Most reactivations caused no symptoms. Still, the team counted six episodes with symptoms, including several cases of shingles in space⁵. Some astronauts carried live chickenpox-shingles virus in their saliva two to six days after landing, a possible risk to newborns and people with weakened immune systems⁵.

Spaceflight is an extreme mix of pressures, so it isn’t a clean test of everyday worry. But stand-ins on Earth, from Antarctic stations to undersea habitats, also showed reactivation, at lower levels⁵.

Chronic stress and inflammation: a real link, smaller than headlines suggest

Long-running stress often gets blamed for “inflammation.” The research supports a link, though a modest one.

A 2023 review pooled 11 long-term studies of workers. Stressful working conditions were linked to higher inflammatory markers, but the association was weak¹⁰. It was clear only for interleukin-6 (IL-6), a signaling protein that rises with inflammation, and every study carried a serious risk of bias¹⁰. The link also shrank the longer people were followed¹⁰.

Depression shows a clearer pattern. Across 58 studies, people with major depression had higher IL-6 and C-reactive protein, a blood marker of inflammation, than people without depression¹¹. Those comparisons show a link, not which came first.

Our chronic stress article covers how scientists tally the body’s wear and tear, and “Inflammation Can Harm Your Heart. An ‘Anti-Inflammatory’ Label Proves Little” explains why product claims deserve a second look.

Stress can blunt a vaccine response, depending on the dose and the stress

The exam study wasn’t a one-off. In 1996, Glaser’s group reported that spousal caregivers had more than a 50% reduction in immune responses to a flu vaccine, and in 2000 that Alzheimer’s caregivers responded poorly to a pneumonia vaccine².

The amount of vaccine may matter. A 1996 study noted that an earlier trial using a low dose of hepatitis B vaccine had found stress reduced antibodies¹². When this team gave the standard dose to 68 volunteers chosen for very high or very low stress, stress made no difference to antibody levels at 2, 6 or 7 months¹².

That fits a broader caution. Glaser and colleagues wrote that stress-related immune changes are generally small and stay within normal ranges³.

In 2021, as COVID-19 vaccines rolled out, Ohio State researchers Annelise Madison and Janice Kiecolt-Glaser reviewed this research. They concluded that depression, stress, loneliness and poor health habits are linked to weaker vaccine responses, and may slow protection and shorten how long it lasts⁹.

Their practical suggestion, drawn from earlier studies rather than tested directly, was vigorous exercise and a good night’s sleep in the 24 hours before a shot⁹. Whether to get any vaccine is your decision. If you choose one, our companion articles on physical activity and on sleep cover what else research says about the days around it.

Tai chi raised immunity to the shingles virus in a 16-week trial

Shingles happens when the dormant chickenpox virus wakes up, usually after age 50, as the National Institutes of Health noted in 2007⁷.

That year, researchers led by Michael Irwin published a trial testing whether tai chi could shore up older adults’ defenses against the virus⁶. They randomly assigned 112 healthy adults aged 59 to 86 to 16 weeks of either Tai Chi Chih classes or health education classes, the comparison group⁶. Each group got 120 minutes of instruction a week⁷.

The researchers tracked how many of each volunteer’s T cells sprang into action when exposed to the virus in a lab test. By week 16, that count had risen 24% in the tai chi group⁶. The education group’s 13% rise could have been chance⁶.

Then everyone got a chickenpox vaccine, because the higher-strength shingles vaccine of the day wasn’t available for the study⁶. Nine weeks later, the tai chi group’s immunity was 38% above where it started, versus 28% in the education group⁶. NIH’s announcement framed the same results another way: tai chi plus the vaccine gave about 40% more immunity than the vaccine alone⁷.

The tai chi group also reported better physical functioning, less bodily pain, more vitality and better mental health⁶. The National Institute on Aging and NIH’s complementary medicine center paid for the work⁶.

The limits are real. Volunteers were healthier than average, knew which group they were in and were followed for only about six months. The trial didn’t count shingles cases⁶. Today’s shingles vaccine is a different product, described in our article on immunity across the lifespan.

Mindfulness and support shift some immune markers, tentatively

In 2016, researchers David Black and George Slavich reviewed 20 randomized trials of mindfulness meditation with 1,602 participants⁸.

The most consistent finding was lower activity of NF-κB, a master switch that turns on inflammation genes inside immune cells, in all three trials that measured it⁸. C-reactive protein fell in three of six trials, two of them only at trend level⁸. People with HIV who practiced mindfulness held on to more CD4 T cells, the cells HIV destroys, in three trials⁸.

Vaccine results were mixed: one trial found a larger flu antibody rise after mindfulness training, another found no change and a third gave split results⁸. Circulating signaling proteins such as IL-6 showed no replicated change⁸. Only 8 of the 20 trials compared mindfulness with an equally engaging activity, and the authors called the findings tentative⁸.

Other people matter too. In the exam study, students who reported more social support mounted stronger responses to the third hepatitis B shot¹. “The right kind of help beats more help, and giving it counts too” covers which kinds of support make a difference.

NCCIH, the federal center for complementary health, says relaxation techniques such as slow breathing and progressive muscle relaxation have some evidence of lowering inflammatory signaling proteins¹⁴. It also notes that a few people feel more anxious during relaxation practice, and that rare reports suggest problems in people with epilepsy, certain psychiatric conditions or a history of trauma¹⁴.

The stress-immunity toolkit

This toolkit is our own design, built from the studies above.

Practice	Measured immune effect	Evidence rating	How to start
Tai chi	Shingles-virus T-cell immunity up 24% in 16 weeks in healthy older adults6	Promising but early	Find a beginner class; the trial used about two hours of instruction a week7
Mindfulness meditation	Lower NF-κB in three trials; mixed results for CRP and vaccines8	Promising but early	Try an app with relaxation exercises13, or a beginner class
Social support	Stronger hepatitis B vaccine response in students reporting more support1	Promising but early	Reach out to friends or family who help you cope13
Slow breathing or muscle relaxation	Some evidence of lower inflammatory signals14	Promising but early	Use a breathing app; switch methods if one makes you more anxious (our suggestion)1314
Exercise and sleep before a chosen vaccine	Suggested by a 2021 review of earlier studies, not tested directly9	Promising but early	Plan a workout and a full night’s sleep the day before9
A steady sleep routine	Covered in our sleep and immunity article	Promising but early	Keep regular bed and wake times13
Supplements sold for “stress and immunity”	No immune-outcome trials among the sources we reviewed	Not enough evidence	See our article on memory, immune and stress formulas before buying

What’s established, and where the evidence stops

Claim	Rating	What it rests on
Long-running stress is linked to broad drops in immune function	Strong evidence	Meta-analysis of 293 studies4
Stress lasting minutes boosts some fast-acting defenses	Strong evidence	Pooled lab studies4
Stress lets dormant herpes viruses reactivate	Promising but early	Antibody studies and astronaut data345
Chronic work stress raises inflammation	Promising but early	Weak link in 11 cohort studies with serious bias10
Stress weakens vaccine responses	Promising but early	Small studies; a standard-dose study found no link1212
Tai chi strengthens immunity to the shingles virus	Promising but early	One trial of 112 older adults6
Mindfulness changes immune markers	Promising but early	20 small trials, tentative results8
Measured immune changes explain why stressed people get sick	Not enough evidence	Little or no evidence in healthy people4

That last row matters most. Stress has been linked to catching colds, as our mind-body article explains, but the 2004 analysis found little or no evidence tying stress-related immune changes in healthy people to disease⁴. The immune system has backups, so a large change in one marker may have small real-world effects⁴.

Most studies here were small and measured cells and antibodies, not infections. A marker that moves in a lab test isn’t a cold you didn’t catch.

So no one should be blamed for getting sick. Natural health has long taught that mind and body are one system, and the research supports that idea. It doesn’t support guilt. Treat calming practices as care for yourself, not a test you failed when you catch the flu.

When to get help

The National Institute of Mental Health says to talk with a health care provider or mental health professional if¹³:

• you’re struggling to cope, or your symptoms won’t go away;
• stress interferes with your everyday life;
• it leads you to avoid doing things;
• it seems to be there all the time.

NIMH lists talk therapy and medication, often used together, as treatment options¹³. “Anxiety responds to therapy, medicine and exercise, and some calming herbs carry real risks” compares the options, and “A simple activity plan treated depression as well as CBT in a big trial” covers low mood. If you already take medicine for anxiety or depression, talk with your prescriber before making any change.

Questions readers ask

The bottom line

Stress reaches the immune system in specific ways. Brief stress tends to rev up fast-acting defenses, while stress that lasts months is linked to broad declines and, in some studies, weaker vaccine responses. Stress can also loosen the body’s hold on dormant viruses. Most of these changes are modest, and whether they explain who gets sick is still unproven.

Tai chi, mindfulness, relaxation and supportive relationships have shifted immune measures in small studies. They’re low-cost ways to care for yourself, not cures. When stress becomes hard to manage, a professional can help, and 988 is there in a crisis.

Related reading

• Stress can reach your immune cells, but positive thinking still can’t cure cancer
• Chronic stress adds up in the body, and two famous studies need a second look
• Your immune system makes you sleepy on purpose, and sleep returns the favor
• Runners were warned of an immune “open window,” but crowds and travel may matter more
• Anxiety responds to therapy, medicine and exercise, and some calming herbs carry real risks

Sources

1. “Stress-Induced Modulation of the Immune Response to Recombinant Hepatitis B Vaccine.” Psychosomatic Medicine, 1992;54(1):22-29 (PubMed abstract). pubmed.ncbi.nlm.nih.gov
2. PsychoNeuroImmunology Research Society. “In Memoriam: Ronald Glaser.” PNIRS, 2019. pnirs.org
3. Glaser R, Rabin B, Chesney M, Cohen S, Natelson B. “Stress-Induced Immunomodulation: Implications for Infectious Diseases?” JAMA, 1999;281(24):2268-2270 (Carnegie Mellon University copy). cmu.edu
4. Segerstrom SC, Miller GE. “Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry.” Psychological Bulletin, 2004;130(4):601-630, foundationsofhealth.org; and American Psychological Association press release, July 4, 2004, apa.org
5. Rooney BV, Crucian BE, Pierson DL, Laudenslager ML, Mehta SK. “Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth.” Frontiers in Microbiology, 2019;10:16. frontiersin.org
6. Irwin MR, Olmstead R, Oxman MN. “Augmenting Immune Responses to Varicella Zoster Virus in Older Adults: A Randomized, Controlled Trial of Tai Chi.” Journal of the American Geriatrics Society, 2007;55:511-517 (UCLA copy). teams.semel.ucla.edu
7. Infection Control Today. “Tai Chi Boosts Immunity to Shingles Virus in Older Adults, NIH-Sponsored Study Reports” (reprint of NIH news release). April 9, 2007. infectioncontroltoday.com
8. Black DS, Slavich GM. “Mindfulness Meditation and the Immune System: A Systematic Review of Randomized Controlled Trials.” Annals of the New York Academy of Sciences, 2016;1373:13-24 (UCLA copy). teams.semel.ucla.edu
9. Association for Psychological Science. “Depression and Stress Could Dampen Efficacy of COVID-19 Vaccines” (on Madison AA, Shrout MR, Renna ME, Kiecolt-Glaser JK, Perspectives on Psychological Science, 2021). January 13, 2021. psychologicalscience.org
10. Eguchi H, Watanabe K, Kawakami N, et al. “Work-Related Psychosocial Factors and Inflammatory Markers: A Systematic Review and Meta-Analysis.” Journal of Psychosomatic Research, 2023;170:111349 (Keio University record). keio.elsevierpure.com
11. Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivimäki M. “Cumulative Meta-Analysis of Interleukins 6 and 1β, Tumour Necrosis Factor α and C-Reactive Protein in Patients With Major Depressive Disorder.” Brain, Behavior, and Immunity, 2015;49:206-215 (UCL Discovery). doi.org
12. Jabaaij L, van Hattum J, Vingerhoets A, et al. “Modulation of Immune Response to rDNA Hepatitis B Vaccination by Psychological Stress.” Journal of Psychosomatic Research, 1996;41(2):129-137 (Erasmus University repository). repub.eur.nl
13. National Institute of Mental Health. “I’m So Stressed Out! Fact Sheet.” NIH Publication No. 20-MH-8125. nimh.nih.gov
14. National Center for Complementary and Integrative Health. “Stress.” NIH, last updated April 2022. nccih.nih.gov
15. 988 Suicide & Crisis Lifeline. “Get Help,” 988lifeline.org; and “988 Day 2026 Talking Points,” August 2026, 988lifeline.org