The DOI matches its Crossref record; 100 of the 102 references it cites were found in a registry or an index.
The influence of sex and gender on the immune response
Abstract
The immune system and its orchestrated response are affected by a multitude of endogenous and exogenous factors, modulators and challenges. One of the most frequent differences described in the immune response is its vigor and activity in females compared to males, leading to the consequent increase in autoimmune conditions seen in the female population as well as differences in the immune response to pathogens and viruses. The following review summarizes our present knowledge on sex differences in the immune response, detailing the hormonal and genetic effects that have been proposed as explanatory mechanisms. Sexual hormones, mostly estrogen but also progesterone and testosterone, affect immune cells quantitatively and qualitatively. Relevant research has focused on the impact of hormones on cytokine production by the different effector cells, as well as impact on immunoglobulin production by B lymphocytes and activity of granulocytes and NK cells. The biological aspects are complemented by research data on the possible modulatory role of the X chromosome. In addition to biological differences, the frequently neglected role of gender as an immunomodulator is introduced and explored. Gender affects all areas of human life and consequently affects the different steps of an immune response. Exposure to various types of antigens, access to health promotion programs and health care, as well as prioritization of health needs and household resource allocation all affect the different response of females and males to immunologic challenges.
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“Inflammatory responses are ste reotypically greater in females, which may be dictated by greater cytokine release due to the location of cytokine and TLR genes on the X-chromosome (Oertelt-Prigione, 2012).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Oertelt-Prigione, 2012
In the citing paper
“Thus, in addition to the immune factors that regulate the complex immunoendocrine network, gender might have a significant function in shaping the immune response [2].”
From Gender-Related Effects of Sex Steroids on Histamine Release and Fc ε RI Expression in Rat Peritoneal Mast Cells (2015) · cites this paper as [2]
In the citing paper
“zolpidem, a sleep medication35, which shows slower drug metabolization and high secondary effects in women, increasing their health risks compared with men34,36,37.”
From Sex and gender differences and biases in artificial intelligence for biomedicine and healthcare (2020) · cites this paper as [37]
Citations
Cites
X-inactivation profile reveals extensive variability in X-linked gene expression in females
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The X-files in immunity: sex-based differences predispose immune responses
Fish, E. N. (2008) · Nature reviews. Immunology · doi:10.1038/nri2394 · Cited by 1,164
Health care and equity in India
Balarajan, Y., Selvaraj, S., & Subramanian, S. V. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61894-6 · Cited by 1,102
Estrogen deficiency and bone loss: an inflammatory tale
Weitzmann, M. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28550 · Cited by 990 · cited 1×
“This is especially relevant at the bonemarrow level [22], however, in a complex in vivo environment the role of estrogen alone is difficult to dissect.”
BackgroundMolecular Biology of the Androgen Receptor
Gelmann, E. P. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.10.018 · Cited by 972
The evolution of sex-biased genes and sex-biased gene expression
Ellegren, H., & Parsch, J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2167 · Cited by 925
A Gender Gap in Autoimmunity: Task Force on Gender, Multiple Sclerosis and Autoimmunity
Whitacre, C. C., Reingold, S. C., O'Looney, P. A., Blankenhorn, E., Brinley, F., Collier, E., Duquette, P., Fox, H., Giesser, B., Gilmore, W., et al. (1999) · Science · doi:10.1126/science.283.5406.1277 · Cited by 851
Sex-specific genetic architecture of human disease
Ober, C., Loisel, D. A., & Gilad, Y. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2415 · Cited by 787
Zhang, J. J., & Smith, K. R. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.9479 · Cited by 758
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Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis
Conforti, F., Pala, L., Bagnardi, V., De Pas, T., Martinetti, M., Viale, G., Gelber, R. D., & Goldhirsch, A. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30261-4 · Cited by 973
How sex and age affect immune responses, susceptibility to infections, and response to vaccination
Giefing, C., Berger, P., Lepperdinger, G., & Grubeck‐Loebenstein, B. (2015) · Aging Cell · doi:10.1111/acel.12326 · Cited by 796
“Partially controversial results were reported regarding hormonal effects on the cytokine secretion pattern of T lymphocytes (reviewed in Bouman et al., 2005; Straub, 2007; Gonzalez et al., 2010; Oertelt-Prigione, 2012).”
BackgroundAustad, S. N., & Fischer, K. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.019 · Cited by 619
“Although there have been numerous studies assessing various aspects of immune responsiveness in adult humans in which females have often proven to have more robust responses (Ferguson et al., 2013; Gubbels Bupp, 2015; Oertelt-Prigione, 2012), there have been few such studies in infants.”
Sex and gender differences and biases in artificial intelligence for biomedicine and healthcare
Cirillo, D., Catuara-Solarz, S., Morey, C., Guney, E., Subirats, L., Mellino, S., Gigante, A., Valencia, A., Rementeria, M. J., Chadha, A. S., et al. (2020) · npj Digital Medicine · doi:10.1038/s41746-020-0288-5 · Cited by 553
Sex and Gender Differences in the Outcomes of Vaccination over the Life Course
Flanagan, K. L., Fink, A. L., Plebanski, M., & Klein, S. L. (2017) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060718 · Cited by 508
Metadata
- Authors
- Oertelt-Prigione, S.
- Venue
- Autoimmunity Reviews
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 11
- Issue
- 6-7
- Pages
- A479-A485
- ISSN
- 1568-9972 (ISSN-L)
- OpenAlex
- W2045019335
- Cited by
- 459
- References
- 102
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 38 · 2023: 28 · 2022: 32 · 2021: 43 · 2020: 45 · 2019: 23 · 2018: 28 · 2017: 35 · 2016: 32 · 2015: 36 · 2014: 37 · 2013: 22 · 2012: 7
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autoimmunity Reviews (publishedVersion)
- PubMed (publishedVersion)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- sex differences in immune response, gender differences, autoimmune disease, sex hormones, estrogen, progesterone, testosterone, cytokine production, antibody production, B cells, granulocytes, natural killer cells, X chromosome, social determinants of health, health care access
- MeSH terms
- B-Lymphocytes, Bone Marrow Cells, Dendritic Cells, Female, Humans, Immunity, Active, Immunologic Factors, Killer Cells, Natural, Male, Sex Factors, Gonadal Steroid Hormones, T-Lymphocytes
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