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Sex differences in the immune system

Understanding the role of sex in health care is highly important since there is a difference between the immune responses of males and females. This is partially due to the effects of hormones - including the levels of progesterone, oestradiol, and androgens [1]. Interestingly, the sex differences occur in both the innate and adaptive immunity (summarizing the previous post, the innate immunity is a quicker general response whereas the adaptive immunity is a specialized response against antigens that are led by B- and T-cells).


Innate Immune System


There are changes in cytokine* levels as well as the number and activity of immune cells [1]. For example [1]:

  • Males can produce higher levels of TNF (a cytokine) in response to stimulation with lipopolysaccharides (a bacterial antigen) [5].

  • Males have a higher number of natural killer (NK) cells during childhood and adulthood but in senior years, the NK cell levels rise in females [1].

  • In childhood, the inflammatory response is generally greater in males but, in adulthood, it is greater in females [1].


Adaptive Immune System


There are also changes in the adaptive immune system. As mentioned before, B-cells produce antibodies whereas T-cells mediate the cellular response. T-cells can be subdivided into CD8+ (also known as cytotoxic T-cells) and CD4+ cells (also known as T-helper cells). CD8+ cells attack and try to eliminate the infected cell directly, while CD4+ cells work in a more indirect way by releasing cytokines and helping with the activation of B-cells, CD8+ cells, and other immune components.

Regarding sex differences in adulthood, females typically have a higher number of CD4+ T-cells and B-cells, whereas males have more CD8+ cells [1]. Hormone levels can also affect the adaptive immune system. In particular, immune cell counts of some T-cells may vary depending on the phase of the menstrual cycle [2].


The sex differences in the immune system impact one’s vulnerability to infections and the rate of autoimmune diseases** [3]. For example, females are typically less susceptible to infections. However, they are more prone to developing some autoimmune diseases, such as lupus and rheumatoid arthritis [4].


In conclusion, there are sex-related differences in our immune response, susceptibility to infections, and prevalence of certain autoimmune diseases. Some of these differences are due to hormone levels. However, there are other factors that should be considered, including the genes in the sex chromosomes, the nutrition, and the microbiome (read this text to learn more).


If you want to read more about how sex might entail a difference in vaccine’s responses, check out this interesting post!


*Cytokines = chemical messengers between cells.


**Autoimmune disease = a disorder where the body "attacks" itself (e.g., when the immune system produces levels of autoantibodies that are too high and they mistakenly attack and damage cells of their own body).



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Written by: Nicole

Edited by: María and Natasha


BioDecoded is a volunteer group committed to sharing accurate scientific information. If you have any questions about this topic or would like to learn more, please comment below or send us your questions.



References:

  1. Klein, S., Flanagan, K (2016). Sex differences in immune responses. Nat Rev Immunol 16, 626–638. Available at: https://www.nature.com/articles/nri.2016.90

  2. Arruvito, L., et. al (2007). Expansion of CD4+CD25+ and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J. Immunol. 178, 2572–2578. Available at: https://pubmed.ncbi.nlm.nih.gov/17277167/

  3. Jacobsen H, Klein SL (2021). Sex Differences in Immunity to Viral Infections. Front Immunol. 12:720952. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438138/

  4. Fairweather D, Frisancho-Kiss S, Rose NR (2008). Sex differences in autoimmune disease from a pathological perspective. Am J Pathol 173(3):600-9. Available at: https://pubmed.ncbi.nlm.nih.gov/18688037/

  5. Moxley G, et al (2002). Sexual dimorphism in innate immunity. Arthritis Rheum 46(1):250-8. Available at: https://pubmed.ncbi.nlm.nih.gov/11817599/


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