Why Men and Women Experience Differences in Immune Function
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STORY AT-A-GLANCE
Women face far higher rates of autoimmune conditions like lupus and multiple sclerosis because of their double set of X chromosome immune genes and the effects of hormones such as estrogen
Men experience more severe viral infections, higher cancer risks, and age-related immune decline in part due to testosterone’s suppressive effects and the gradual loss of Y chromosomes in immune cells
Hormones shift immunity across life stages, meaning puberty, pregnancy, menopause, and andropause all create unique windows of higher or lower disease risk that you can plan around
Environmental factors such as diet, toxin exposure, and gut health interact with your genetic and hormonal makeup, shaping how your immune system handles inflammation and infection
Precision strategies based on sex-specific biology allow you to lower risks — women can focus on reducing autoimmune triggers, while men benefit from strengthening defenses against severe infections and cancer
Autoimmune conditions like lupus, characterized by fatigue, joint pain, and organ inflammation, or multiple sclerosis, which damages your brain and spinal cord leading to weakness and numbness, disproportionately strike women compared to men. The numbers are staggering: women are 2.5 times more likely to develop multiple sclerosis and nine times more likely to develop lupus than men.1
Every cell in your body carries either XX chromosomes if you're female or XY chromosomes if you're male, and this genetic blueprint directly influences your immune system. Erica Ollmann Saphire, Ph.D., at La Jolla Institute, explains that the X chromosome carries many immune-related genes, and women effectively have a "double palette" of immune instructions.2
This double dosage strengthens defenses against viruses like SARS-CoV-2 but also raises the risk of the immune system turning against the body itself. Hormones are another key factor. Estrogen, testosterone, and progesterone do far more than regulate reproduction — they act directly on immune cells, dictating which genes turn on or off.
For example, estrogen amplifies antibody production, boosting your defense against pathogens, but at certain levels it also sparks inflammation that drives autoimmune conditions. Testosterone, by contrast, tends to dampen immune activity, reducing inflammation but leaving men more vulnerable to infections. Such differences explain why men are more likely to face severe outcomes from viral diseases like COVID-19, while women live with higher rates of chronic autoimmune disorders.
A scientific review published in Science underscores this point by showing how sex-based differences extend down to the tissue level, shaping responses in organs such as your lungs and brain.3 These findings set the stage for understanding why the immune system works differently in men and women and why those differences matter when you think about disease risk.
Sex Differences Shape Tissue Immunity
In a review published in Science, researchers examined how genetics, hormones, and environmental exposures alter immune responses in tissues such as the lungs, brain, and skin.4 The review highlighted that these differences are not abstract — they explain why men and women experience organ-specific infections, autoimmune diseases, and cancers in distinct ways.
Women carry double the immune-related genetic material — Because females have two X chromosomes, they inherit a broader set of immune-related genes compared to males with one X and one Y chromosome. This means a woman's immune system is equipped with a "double dosage" of immune defenses, giving her stronger protection against infections but also increasing the risk of autoimmune conditions like lupus and multiple sclerosis.
Female immune cells show a mosaic effect — Unlike males, women's cells randomly switch which X chromosome is active, creating a patchwork of immune cells that respond in slightly different ways. This mosaic adds resilience because pathogens face a more diverse defense system, but it also raises the chances that some of those immune cells overreact, triggering autoimmune disease.
Sex hormones tell immune cells how to behave — Hormones such as estrogen and testosterone act directly on immune cells, influencing which genes turn on or off. Estrogen boosts the strength of immune responses, improving defense against bacteria and viruses, while testosterone suppresses immune activity, lowering inflammation but leaving men more prone to severe viral infections.
Environmental factors further shape these immune differences — Nutrition, chemical exposures, and differences in the skin and gut microbiomes between men and women all influence how immune systems function. The review emphasized that lifestyle and environmental choices interact with sex-linked biology, which means factors like diet quality or toxin exposure affect men and women differently.
The future of precision medicine — By understanding these differences at the tissue level, scientists argue that treatments for cancer, autoimmune disorders, and infections should be tailored by sex. As Sonia Sharma, Ph.D., co-author of the review, noted, "When it comes to medicine, one size doesn't fit everybody."5 This points toward therapies designed not just for the disease itself but for how your sex shapes immune responses to that disease.
How Men's and Women's Immune Systems Differ
Disease risks look very different for men and women. Scientists at the La Jolla Institute for Immunology point out that while women make up the majority of autoimmune disease cases, men are more likely to develop heart diseas
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