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Immunology of Stress: A Review Article
Open accessAbstract
Stress significantly impacts the immune system, affecting susceptibility to illness and overall health. This review examines the intricate relationship between stress and the immune system, offering insights having practical implications for health and disease prevention. Stress can significantly trigger molecular and immune modulation, affecting the distribution and trafficking of immune cells in various organs and altering their composition in the blood. The review delves into two key pathways connecting stress and immunity: the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system. Stress activates the neuroendocrine system and triggers microglia in the brain, releasing stress hormones and neurotransmitters that modulate the function and movement of immune cells. Acute stress can temporarily strengthen immunity and promote protection during infection; in contrast, chronic stress dysregulates or inhibits immune functions. Chronic stress causes an increase in cortisol levels through the HPA axis, ultimately suppressing the immune response. Recognizing stress triggers and implementing effective stress management techniques can significantly impact individuals’ well-being. This review indicates that immune cells express genes differentially in response to stress, suggesting individual variabilities in the immune response against stress. This underscores the need for a personalized approach to stress management. This review also highlights the potential link between chronic stress and autoimmune disorders and warrants further investigation.
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![Figure 1 Pathways connecting stress to immune function. Stress activates the HPA axis and SNA, releasing catecholamines (noradrenaline) and glucocorticoids. These hormones alter immune cell behavior, increasing inflammatory cytokines and redistributing immune cells. This has effects on organs like the spleen and gastrointestinal tract, potentially influencing the microbiome. Abbreviations: IL: interleukin; Th17: T helper lymphocyte 17; CXCL12: homeostatic chemokine ligand; β2/β3-AR: β2/β3-adrenoceptors; Ach: acetylcholine; α7nAChR: α7 nicotinic acetylcholine receptor; HPA: hypothalamic–pituitary–adrenal axis; SNS: sympathetic nervous system; NA: noradrenaline; GC: glucocorticoids. Adapted from Ishikawa and Furuyashiki (2022) [36].](/paper-figures/2495783e07fa4892bd3efd66fa7b2b87/immunology-of-stress-a-review-article-figure-1.jpg)
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“Recent studies indicate that chronic psychological or physiological stress can exacerbate RA through neuro–immune–bone axis pathways [76]”
From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [76]
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Resveratrol as a Neuroprotective Bridge from Blue Zone Longevity to Alzheimer's Prevention
Liu, R. (2026) · Theoretical and Natural Science · doi:10.54254/2753-8818/2026.36488
Kim, Y., Kim, J., & Yang, J.-H. (2026) · Annals of Occupational and Environmental Medicine · doi:10.35371/aoem.2026.38.e29
“24-26”
Collinet, A. C. T., Kuipers, M. F., Laurila, R., Remy, M. L., Prevaes, É., van Oudheusden, M. P., Pittens, C. A. C. M., de Vries, S., Verduijn, M., de Groot, N. M. S., et al. (2026) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwag483
Cortisol levels during paediatric endoscopic surgery: results of a pilot study
Nasirov, M., Vivek, K., & Saxena, A. K. (2026) · Journal of Pediatric Endoscopic Surgery · doi:10.1007/s42804-026-00320-3
Prediction models for infection after kidney transplantation: a systematic review
Zhao, X., Zhang, Y., Tang, H., Long, J., Dong, H., Kuang, G., & Song, J. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1916764
“Chronic psychological stress elevates glucocorticoid levels via the hypothalamic-pituitary-adrenal axis and the sympatho-adreno-medullary system, thereby suppressing cellular immune function (68).”
SCIENCE OF STRESS AND ITS COPING MECHANISMS
Panebi, U. G. O., & Hamilton‐Ekeke, J. (2026) · Journal of Educational Research and Development · doi:10.67203/jerd.2026.dv6p68pv
Hagos, B. T., Weldemedhn, S. G., Geto, R. G., Wordofa, K. D., Meshesha, G. A., Abera, A. A., Kebede, E. M., Amare, K., & Berhe, B. M. (2026) · IDCases · doi:10.1016/j.idcr.2026.e02780
“…blunted in this patient, a phenomenon supported by psychoneuroimmunological evidence linking chronic systemic disease to HPA axis suppression [7], modern frameworks on stress vulnerability and cortisol hypo-responses to acute stress [17], and data demonstrated specifically in leprosy cohorts…”
Antigen presentation and its evolution in teleost fishes
Wong‐Benito, V., Chen, Y., & Dixon, B. (2026) · Fish physiology · doi:10.1016/bs.fp.2026.08.005
Bihorac, J., & Hadamitzky, M. (2026) · NeuroImmunoModulation · doi:10.1159/nim/adxag008
Hasan, A., Asfour, A. A. R., Qaba, H., AL-Sharabi, A. A., ASFOOR, A., Sarhan ONDOKUZ MAYIS UNIVERSITY MOHAMMED, Al-Adhreai, A., Güner, S., & Saeedy, M. A. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06173-4
“…and thalamus, mast cells engage with adjacent neurons and astrocytes under normal physiological conditions to help modulate the release of neuroendocrine mediators such as CRH and neuropeptide Y, processes that play a role in regulating circadian rhythms, appetite, and the stress response [98].”
Pallett, S. J. C., Woolley, S., Wadda, K., Hemingway, R., Walsh, N. P., Moore, L. S. P., O’Shea, M. K., & Macallan, D. C. (2026) · BMJ Immunology · doi:10.1136/bmjimm-2025-000015
Samalia, P. D., Chen, S. S. L., Lu, L. M., Sims, J. L., Lindsay, K., & Niederer, R. L. (2026) · Journal of Personalized Medicine · doi:10.3390/jpm16100511
“Sleep, psychological stress and circadian disruption influence immune homeostasis through interactions among the hypothalamic–pituitary–adrenal axis (HPA), sympathetic nervous system and immune system [21–27].”
Sari, A. M., Fauzi, M., Dharmawan, Y., & Fitriani, B. N. (2026) · Contagion Scientific Periodical Journal of Public Health and Coastal Health · doi:10.30829/contagion.v8i3.29314
“This stress can weaken the adaptive immune response, increasing susceptibility to infection (Ali et al., 2025; Alotiby, 2024; Morrone et al., 2020).”
Inhibition of Adrenergic Receptors Reduces Genital HSV-1 Clinical Recurrences in Guinea Pigs
Green, J. C., Moore, G. A., Irwin, M. D., Joyce, J. D., & Bertke, A. S. (2026) · Viruses · doi:10.3390/v18101081
“Chronic stress, characterized by prolonged elevation of cortisol, causes immune suppression [22] but also directly reactivates latent HSV-1 in cultured neurons [10].”
Mastrofini, G. F., Romersi, R. F., Lombardi, M. G., Persaud, K. T., Ryan, M. M., Hirsch, K. R., Fraley, A. L., Dawes, J. J., Stray-Gundersen, S. O., Hardin, J. W., et al. (2026) · Journal of the International Society of Sports Nutrition · doi:10.1080/15502783.2026.2740227
“Both chronic stress and poor sleep are associated with decrements in health, well-being, and daily occupational performance [4,5].”
Uncu, Y. M. G., & Leydis, M. R. (2026) · Frontiers in Psychology · doi:10.3389/fpsyg.2026.1884838
“…axis, cortisol reactivity and recovery, sleep quality and fatigue, pain, inflammatory and neuroimmune signaling, metabolic state, sensory load, and the calibration of stress-response systems (Agorastos et al., 2023; Alotiby, 2024; Herman et al., 2012; James et al., 2023; Khalsa et al., 2018).”
Meta-Inflammation in Type 2 Diabetes Mellitus: Theoretical, Methodological, and Clinical Aspects
Zhuravleva, Y. A., & Gusev, E. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198891
Algül, N. I. E., Erzurum, M., Felekoğlu, M. A., Özerdem, M. E., Özbeyaz, N. B., & Algül, E. (2026) · Angiology · doi:10.1177/00033197261494019
Mogharebi, R. S., & Sabet, M. (2026) · Journal of Cognition Behavior Learning · doi:10.61838/jcbl.387
Darras, G., Desmet, M., Schoutens, W., Debeer, D., Lamont, A. E., Bhattacharya, J., & Annemans, L. (2026) · Frontiers in Psychology · doi:10.3389/fpsyg.2026.1765017
“…functioning in complex and multifactorial ways, including increased inflammation, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and nervous system, and changes in the microbiome (Marwaha et al., 2025; Warren et al., 2024; Morys et al., 2024; Alotiby, 2024; Nunez et al., 2025).”
Immune regulation of dormancy and metastatic progression in breast cancer
Sabol, H. M., & Borriello, L. (2026) · npj Breast Cancer · doi:10.1038/s41523-026-01077-x
ПСИХОЛОГИЧЕСКИЙ СТРЕСС И ИММУННАЯ СИСТЕМА ЧЕЛОВЕКА: ОБЗОР СОВРЕМЕННЫХ ИССЛЕДОВАНИЙ
Коршубаева, Р. Х. (2026) · Buxoro xalqaro universiteti ilmiy axborotnomasi · doi:10.67780/buxoro-xalqaro-universiteti-ilmiy-axborotnomasi.2026.f461bab7
Міщенко, В. П., & Міщенко, В. В. (2026) · Reproductive Endocrinology · doi:10.18370/2309-4117.2026.85.16-24
Petrushko, M. P., Klyushnikov, Y. V., Панасовський, М. Л., Klimukhina, O. I., & Yurchuk, T. O. (2026) · Eastern Ukrainian Medical Journal · doi:10.21272/eumj.2026;14(3);856-863
Guo, D., Wang, C., Yang, N., & Liu, Y. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48111135
Valovatsky, E., Patel, Z., & Jain, P. (2026) · NeuroImmune Pharmacology and Therapeutics · doi:10.1515/nipt-2026-0023
“An individual’s allostatic load is comprised of the alterations in metabolic demand, hormonal and immune signaling, and the changes in emotional and cognitive processing that underlie the development of adaptive behaviors for responding to future encounter of similar stressors [25].”
Гейн, С. В., & Ibatullin, M. V. (2026) · Russian Journal of Immunology · doi:10.46235/1028-7221-17411-tro
Sadurska, G., Psiuk, M., Prusaczyk-Świerzewska, A., Hunek, O., Gajewska, K., Januszewska, N., Matuszewski, P., Ziółkowska, J., Kleparska, A., & Smędowski, I. (2026) · Quality in Sport · doi:10.12775/qs.2026.78.76475
Metadata
- Authors
- Alotiby, A.
- Affiliations
- Umm al-Qura University (SA)
- Corresponding author
- Alotiby, Amna
- ORCID
- Alotiby, Amna
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2024-10-25
- Volume
- 13
- Issue
- 21
- Pages
- 6394
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC11546738
- OpenAlex
- W4403749058
- Cited by
- 253
- References
- 51
- Citations by year
- 2026: 145 · 2025: 108
- FWCI
- 9.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- stress, immune system, hypothalamic-pituitary-adrenal axis, sympathetic nervous system, cortisol, chronic stress, acute stress, immune cell trafficking, neuroendocrine-immune interaction, microglia, stress hormones, stress management, autoimmune disease, immune gene expression
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