The notion of “man flu,” often invoked humorously to describe men’s tendency to amplify the effects of a cold or minor ailment, may be familiar to many. However, an underlying reality that may not be as widely recognized is the fact that women generally exhibit more robust immune responses to infections than their male counterparts. This biological disparity has broader implications, potentially rendering women more susceptible to certain chronic illnesses arising from immune system dysfunction.
In a nuanced exploration, we delve into the intricate interplay of biological elements that contribute to divergent immune responses between men and women, and how these dynamics influence women’s health. While acknowledging the potential influence of both sex and gender on immune reactions, the scope of this article centers on the biological dimension of sex rather than gender.
A Complex Duel: Immune Disparities Between Genders
At each juncture of the immune response, disparities between sexes emerge, encompassing factors such as immune cell count, activation levels (readiness to counter challenges), and beyond. However, this narrative extends beyond mere simplicity. Our immune system undergoes continuous evolution throughout our lifespans, assimilating lessons from past encounters while adapting to the physiological transformations associated with aging. Thus, distinctions in the immune system’s behavior in relation to sex persist from infancy through puberty, maturation, and into advanced age.
The X Factor: Deciphering Chromosomal Influence
A pivotal element in comprehending these discrepancies lies within the X chromosome. Females possess two X chromosomes, while males bear one X and one Y chromosome. The X chromosome houses a significant array of immune-related genes. Furthermore, approximately 118 genes within a specific gene family on the X chromosome hold the capacity to modulate gene expression or alter protein synthesis, a cohort including components vital to immunity. Termed microRNA, these gene-protein regulators are notably sparse on the Y chromosome, with only two microRNA genes present.
Given that the X chromosome outnumbers the Y chromosome in gene count (approximately 900 versus 55), female cells have evolved a mechanism to deactivate one of their X chromosomes. This process, akin to adjusting a dimmer rather than flicking a light switch, results in 15-25% of genes on the silenced X chromosome being active at any given time within a particular cell. Consequently, female cells often express a higher number of immune-related genes and gene-protein regulators in comparison to their male counterparts. This differential gene expression translates into expedited pathogen clearance within females compared to males.
Hormonal Dimensions: An Intricate Nexus
Beyond genetic disparities, sex hormones contribute to the intricate web of immune differences between men and women. Progesterone and testosterone are broadly recognized as agents that temper immune responses. Though present in both males and females, progesterone exhibits heightened levels in non-menopausal women vis-à-vis men, whereas testosterone surges more markedly in males than females.
Oestrogen, a pivotal female sex hormone, introduces a layer of complexity. While it generally enhances immune responses, its levels fluctuate throughout the menstrual cycle, surge during pregnancy, and diminish post-menopause. This hormonal landscape, in tandem with genetic nuances, leads to elevated immune responses during pregnancy and its aftermath, providing an evolutionary advantage that safeguards both maternal and progeny wellbeing. This adaptive pattern resonates not only in humans but also extends to diverse species such as insects, reptiles, birds, and mammals.
Unraveling Consequences: Immune Responses and Disease Dynamics
Women’s heightened immune responsiveness to infections, while advantageous in certain scenarios, also comes with heightened susceptibility to specific diseases and prolonged immune reactions following infections. A staggering 75-80% of immune-mediated inflammatory diseases manifest in females. Conditions more prevalent among women encompass multiple sclerosis, rheumatoid arthritis, lupus, Sjogren’s syndrome, and thyroid disorders like Graves disease.
In these afflictions, the immune system perpetually confronts what it perceives as foreign intruders. However, this perception often errs, targeting host cells or tissues as adversaries. Consequently, tissue damage, pain, and mobility issues ensue.
Chronic inflammation subsequent to infections is also more conspicuous in women. Instances include the development of chronic fatigue syndrome following infections with Epstein Barr virus or Lyme disease, both of which exhibit a higher prevalence in women than men.
These insights shed light on the heightened risk faced by pre-menopausal women of enduring long COVID symptoms subsequent to SARS-CoV-2 infection – a phenomenon that underscores the intricate interplay of immune responses and gender-specific health outcomes.
Research has also revealed the presence of auto-antibodies (antibodies that attack the host) in patients with long COVID, suggesting it might be an autoimmune disease. As women are more susceptible to autoimmune conditions, this could potentially explain the sex bias seen. However, the exact causes of long COVID, and the reason women may be at greater risk, are yet to be defined.
