XX or XY: For Better or For Worse

XX or XY: For Better or For Worse

Are there sex differences in the human immune system?  Yes, there are.  Women have stronger immune systems than men.  But, similar to a coin this presents two sides.  Women are less likely to catch infections and develop cancer, and if they do the infection tends to be less severe than in men.  This has been well demonstrated during the Covid pandemic.  But, the other side of the coin is that women are more likely to suffer auto-immune diseases than men. 

The two main reasons for the difference are hormones and genes.  Estrogen broadly stimulates immune function.  In terms of infection risk and cancer risk, this is a good thing.  But in terms of auto-immune issues it’s a bad one.  On the other hand, testosterone has a mild immune weakening effect. 

With regards to genes, the X chromosome contains the large majority of the genes that control immune function (over 80% of them).  Women have two X chromosomes; one from their mom and one from their dad.  While, men have a single X chromosome (from their mom).  Now the interesting thing is that women have only one of their X chromosomes active in individual cells, the other one is inactive.  Therefore 50% of a women’s cells have their mom’s X chromosome and 50% of their dad’s.  This is called mosaicism.  This genetic diversity gives women a broader repertoire of immune function.  As the saying goes, there are exceptions to every rule.  And as it turns out not all genes on the inactivated X chromosome are switched off.  Some immune system genes remain functional on both X chromosomes.  An important example is the gene that controls production of toll-like receptor 7 (TLR7).  TLR’s recognize invading microbes and induce the production of inflammatory cytokines and interferons to kill them. 

In terms of auto-immune conditions women are more prone.  Since their immune system is stronger this can be a disadvantage if that strength is not appropriately controlled.  The other issue goes back to this mosaicism.  Going back to fetal life the human immune system is “trained” to recognize

its own cells (self-recognition).  Because women are mosaics of two populations of genetically different cells this “training”    

process is less efficient.  This in turn can lead to accidentally attacking one’s self i.e., auto-immunity. 

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