The female sex has a more potent immune system

There is an outstanding biological sex difference in humans, the basis of which derives from differences in steroid hormone function,  and which makes itself felt in virtually every aspect of immune function.    This sex difference is easy to summarize:  the human female has a stronger immune system than the human male.   We have already seen that the human male is more susceptible to infections of just about every sort. To judge this, it is important to be aware of numerous complex social variables:  there are, in numerous countries, biases against the female sex (clitoridectomy practiced under non-sterile surgical conditions for example, improper medical diagnosis and health care, etc.).  Women may be more exposed to childhood diseases due to closer contact with children.  Sex-specific behavior may place men at risk for infections (use of infected needles in drug addiction,  exposure to the AIDS virus through homosexual encounters,  weakening of the immune system through unhealthy lifestyle such as alcoholism and smoking,  etc.).   Studies of infection of the fetus by the mother helps circumvent most of these confounds.   For example, more male than female fetuses contract the AIDS virus from their mother's blood.  While girls are more at risk for a few infectious diseases (whooping cough, chickenpox, rubella),  boys are at greater risk for the vast majority of infections (infectious diarrhea, respiratory infection, enterobius vermicularis infection, otitis,  B-viral hepatitis, tuberculosis, etc.).   The male/female ratio for tuberculosis (an infectious disease) in 1969,  in the U.S.,  was 3:1. 

On the other hand, the human female is more susceptible to virtually every auto immune disease known to exist.  An auto immune disease consists of an excessive response of the immune system to one or several of one’s own body tissues.  This sex difference in overall immune function is very basic.  It is clearly manifest at the cellular level, most cellular immune parameters indicating greater immune vitality in the female sex. 

Student’s tribune:   Men’s and women’s immune systems are very different

The reader may recall my account,  in chapter 1, of an investigation by my student Alain St-Marseille.   His blood samples of 400 men and 400 women with brain disease differed significantly with respect to immune parameters.  He found that the sexes differed in immune parameters in a manner specific to each disease.  The diseases included brain hemorrhage, thrombotic infarct (obstruction of a vessel by stenosis or thinning of the blood passage), embolus (obstruction of a vessel by a clot), transient ischemia (temporary obstruction of a blood vessel), primary brain cancer, metastatic tumors in the brain,  and migraine. Using twenty-two standard blood parameters printed out by the Coulter machine, Alain was able to correctly classify 92% of his subjects into the appropriate sex.  Overall,  his interpretation of the sex-specific profiles was that the female sex has a stronger immune system.  For example, in Alain’s database,  as reported previously in normal subjects, women had higher neutrophil and platelet counts than men. Platelets are an important component, in blood, of the inflammatory response and neutrophils are a special type of immune cell very common in blood.

Though prepubertal boys have more allergies (overactivity of the immune system not classified as auto immune disorders),  post-pubertal females are, in fact, three times more at risk for developing allergies.   Finally,  gender differences in immune function have become apparent from statistics pertaining to relative success rates of organ transplants from same-  versus opposite-sexed humans and rodents. Heart or lung transplants from women to men are rejected more than from men to men.   Bone marrow transplants from men to women are rejected more than from women to women.  Early transplant studies (done in the 1950s) using inbred mice  found that 100% of the female -> male skin grafts took, whereas none  of the male -> female skin grafts were successful.

In vitro studies (studies of body liquid or tissue samples in a dish) have shown that under varying conditions,  and depending on the types of tissues sampled,  adding estrogen to tissue samples increases the production of both T lymphocytes (immune cells of thymic origin) and B lymphocytes (immune cells of bone marrow origin).  The white cell (lymphocyte) count is highest in normal cycling women at ovulation,  indirectly suggesting,  again,  an immunofacilitatory role of estrogen which peaks at ovulation.  One study found that women tend to catch infections more during menstruation than around ovulation.   Finally,  estrogen may not be the only steroid hormone capable of modulating immune function.  Testosterone seems to produce the opposite effect:  it weakens the immune system.   For example,  men with an extra X chromosome,  known as bearers of Klinefelter’s syndrome (the XXY karyotype) frequently present with reduced testosterone levels and normal male levels of estrogen.  However,  the female hormones luteinizing hormone and follicle-stimulating hormone may be abnormally high relative to normal men in men with Klinefelter syndrome.  They are more at risk than normal men for auto immune diseases such as lupus,  Basedow’s disease, sclerodermia, Sjögren’s disease, and spondylarthritis. 

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This case of Klinefelter’s syndrome (with confirmed XXY karyotype)  presents the eunuchnoid body morphology (gender ambiguity),  micropenis,  gynecomastia,  disproportionately long legs and  tallness.
 Steroid hormones indeed play a modulatory role in immunity and in auto immunity.  This is reflected in the fact that auto immune diseases are aggravated at the luteal phase of menstruation, or postpartum, or by the administration of additional estrogen.  The female prevalence of auto immune disease is a major cause of chronic pain -thus truly influencing the quality of life of many women.  It is a major source of medical complaints,  and explains the 40% higher rate of female consultation of doctors -at least in North America and Europe,  and probably everywhere that women have a life expectancy above fifty years.   The overarching sex difference in the immune system that I have just mentioned bears upon our prime concern in this book, sex differences in brain-behavior relations,  in three important ways.   First,  we have come to realize only in the last twenty years or so, that the immune system influences brain development,  including embryonic and fetal development.  So if there is a basic difference in the immune system before birth,  then this could have significant repercussions on the development of the brain and of behavior.   Second,  several of the auto immune diseases attack brain systems,  and are, thus, an issue for clinical neuropsychology, and for the neuropsychological study of sex differences.  Third,  to the extent that nothing influences behavior more than death (except birth),  the human male's weak immunity is an important risk factor for infection,  encephalopathy, and death.

Why would it be adaptive for mammals to have greater immunity in females than in males ?   An evolutionary explanation would have to be based on an analysis of the differences in life experience of the two sexes and of their distinct ecological niches.   Differences between the sexes which would seem relevant are the following:  1) a single female  typically gets penetrated by several potentially germ-carrying penises,  2) females bring the progeny to term in their womb,  an environment which could potentially be mobilized to protect the progeny from antigens and also from maternal diseases which could threaten the progeny she is carrying, 3)  gestating females could themselves be poisoned by their own offspring, who, after all, contain tissues which are new to the mothers' immune repertory,  but could also develop special forms of self-protection, 4) females are exposed to germs during parturition and must be particularly enhanced in their immune function at this time, and 5) females must feed the babies with their own milk which could be a potential carrier of diseases and toxins, life-threatening for the progeny, or of special antibodies handed down to the next generation.