Review Article | Published:

Sex differences in immune responses

Nature Reviews Immunology volume 16, pages 626638 (2016) | Download Citation

Abstract

Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.

Key points

  • Sex is a biological variable that affects the functions of the immune system.

  • Sex differences occur in both innate and adaptive immune responses and are evolutionarily conserved across diverse species.

  • Sex differences in immune responses change throughout life and are influenced by both the age and reproductive status of an individual.

  • Sex chromosome genes and sex hormones, including oestrogens, progesterone and androgens, contribute to the differential regulation of immune responses between the sexes.

  • Environmental factors, including nutrition status and the composition of the microbiome, also alter the development and functioning of the immune system differently in males and females.

  • Sex differences in immune responses result in differential susceptibility of males and females to autoimmune diseases, malignancies and infectious diseases, as well as affecting the outcome of vaccination.

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Acknowledgements

The authors thank O. Hall and J. Peretz for assistance with tables, A. Pekosz and M. Plebanski for constructive comments on an earlier draft, and three anonymous reviewers who provided feedback that assisted with improving this Review.

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Affiliations

  1. Departments of Molecular Microbiology and Immunology, and Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205 USA.

    • Sabra L. Klein
  2. Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3004, Australia.

    • Katie L. Flanagan

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The authors declare no competing financial interests.

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Correspondence to Sabra L. Klein.

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https://doi.org/10.1038/nri.2016.90

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