Eventually, he found a postdoctoral position in the lab of one of his thesis committee members. And in the years since, when he’s set up his own lab at the university’s Bloomberg School of Public Health, he’s carefully argued that sex, defined by biological attributes like our sex chromosomes, sex hormones and reproductive tissues, actually influences immune responses.
Through research in animal and human models, Klein and others have shown how and why male and female immune systems respond differently to the flu virus, HIV and certain cancer therapies, and why most of women receive greater protection from vaccines, but are also more likely to suffer from severe asthma and autoimmune disorders (which had been known but not specifically attributed to immune differences). “The work in his lab has been instrumental in advancing our understanding of vaccine responses and immune function in men and women,” says immunologist Dawn Newcomb of Vanderbilt University Medical Center in Nashville, Tennessee. (When referring to people in this article, “male” is used as shorthand for people with XY chromosomes, a penis and testicles, and who go through testosterone-dominated puberty, and “female” is used as (shorthand for people with XX chromosomes and a vulva, and going through an estrogen-dominated puberty.)
Through her research, as well as the unglamorous work of organizing symposia and meetings, Klein has helped lead a shift in immunology, a field that long thought sex differences didn’t matter. Historically, most trials enrolled only men, which had incalculable, and probably incalculable, consequences for public health and medicine. The practice, for example, has resulted in women being denied life-saving HIV therapy and has left them susceptible to worse side effects from drugs and vaccines when given the same dose as men men
Men and women do not experience infectious or autoimmune diseases in the same way. Women are nine times more likely to have lupus than men, and have been hospitalized at higher rates for some strains of the flu. Meanwhile, men are more likely to get TB and die from covid-19 than women.
In the 1990s, scientists often attributed these differences to gender rather than sex: to norms, roles, relationships, behaviors and other sociocultural factors as opposed to biological differences in the immune system.
For example, although three times as many women as men have multiple sclerosis, immunologists in the 1990s ignored the idea that this difference might have a biological basis, says Rhonda Voskuhl, a neuroimmunologist at the University of California, Los Angeles. “People would say, ‘Oh, women just complain more, they’re kind of hysterical,'” Voskuhl says. “You had to convince people that it wasn’t just subjective or environmental, that it was basic biology. So it was a battle difficult”.
Despite the historical practice of “bikini medicine” (the notion that there are no major differences between the sexes outside of the parts that fit under a bikini), we now know that whether you’re looking at your metabolism, heart, or system immune, there are both biological gender differences and sociocultural gender differences. And both play a role in disease susceptibility. For example, men’s greater propensity for tuberculosis (they are almost twice as likely to get it as women) can be attributed in part to differences in their immune responses and in part to the fact that men are more prone to to smoke and work in mining or construction. jobs that expose them to toxic substances, which can affect the immune defenses of the lungs.
How to differentiate the effects of sex and gender? This is where animal models come in. “Gender is a social construct that we associate with humans, so animals don’t have gender,” says Chyren Hunter, associate director of basic and translational research at the US National Institutes of Health’s Office of Research on Women’s Health Seeing the same effect in both animal models and humans is a good starting point for finding out whether an immune response is modulated by sex.