How biological differences between men and women alter immune responses and affect women's health
Birmingham (The Conversation): Most people will have heard the term "man flu", which refers to men's perceived tendency to exaggerate the severity of a cold or a similar minor ailment.
What most people may not know is that, generally speaking, women mount stronger immune responses to infections than men.
Men are more susceptible to infections from, for example, HIV, hepatitis B, and Plasmodium falciparum (the parasite responsible for malaria).
They can also have more severe symptoms, with evidence showing they're more likely to be admitted to hospital when infected with hepatitis B, tuberculosis, and Campylobacter jejuni (a bacteria that causes gastroenteritis), among others.
While this may be positive for women in some respects, it also means women are at greater risk of developing chronic diseases driven by the immune system, known as immune-mediated inflammatory diseases.
Here we will explore how biological factors influence immune differences between the sexes and how this affects women's health.
While we acknowledge that both sex and gender may affect immune responses, this article will focus on biological sex rather than gender.
Battle of the sexes
There are differences between the sexes at every stage of the immune response, from the number of immune cells, to their degree of activation (how ready they are to respond to a challenge), and beyond.
However, the story is more complicated than that. Our immune system evolves throughout our lives, learning from past experiences, but also responding to the physiological challenges of getting older.
As a result, sex differences in the immune system can be seen from birth through puberty into adulthood and old age.
Why do these differences occur? The first part of answering this question involves the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. The X chromosome contains the largest number of immune-related genes.
The X chromosome also has around 118 genes from a gene family that are able to stop the expression of other genes, or change how proteins are made, including those required for immunity.
These gene-protein regulators are known as microRNA, and there are only two microRNA genes on the Y chromosome.
The X chromosome has more genes overall (around 900) than the Y chromosome (around 55), so female cells have evolved to switch off one of their X chromosomes. This is not like turning off a light switch, but more like using a dimmer.
Around 15-25 per cent of genes on the silenced X chromosome are expressed at any given moment in any given cell.
This means female cells can often express more immune-related genes and gene-protein regulators than males. This generally means a faster clearance of pathogens in females than males.
Second, men and women have varying levels of different sex hormones.
Progesterone and testosterone are broadly considered to limit immune responses.
While both hormones are produced by males and females, progesterone is found at higher concentrations in non-menopausal women than men, and testosterone is much higher in men than women.
The role of oestrogen, one of the main female sex hormones, is more complicated. Although generally oestrogen enhances immune responses, its levels vary during the menstrual cycle, are high in pregnancy and low after menopause.
Due in part to these genetic and hormonal factors, pregnancy and the years following are associated with heightened immune responses to external challenges such as infection.
This has been regarded as an evolutionary feature, protecting women and their unborn children during pregnancy and enhancing the mother's survival throughout the child-rearing years, ultimately ensuring the survival of the population.
We also see this pattern in other species including insects, lizards, birds and mammals.
What does this all mean?
With women's heightened immune responses to infections comes an increased risk of certain diseases and prolonged immune responses after infections.
An estimated 75-80 per cent of all immune-mediated inflammatory diseases occur in females.
Diseases more common in women include multiple sclerosis, rheumatoid arthritis, lupus, Sjogren's syndrome, and thyroid disorders such as Graves disease.
In these diseases, the immune system is continuously fighting against what it sees as a foreign agent.
However, often this perceived threat is not a foreign agent, but cells or tissues from the host. This leads to tissue damage, pain and immobility.
Women are also prone to chronic inflammation following infection.
For example, after infections with Epstein Barr virus or Lyme disease, they may go on to develop chronic fatigue syndrome, another condition that affects more women than men.
This is one possible explanation for the heightened risk among pre-menopausal women of developing long COVID following infection with SARS-CoV-2, the virus that causes COVID.
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.
This paints a bleak picture, but it's not all bad news. Women typically mount better vaccine responses to several common infections (for example, influenza, measles, mumps, rubella, hepatitis A and B), producing higher antibody levels than men.
One study showed that women vaccinated with half a dose of flu vaccine produced the same amount of antibodies compared to men vaccinated with a full dose.
However, these responses decline as women age, and particularly after menopause.
All of this shows it's vital to consider sex when designing studies examining the immune system and treating patients with immune-related diseases.
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Trouble ‘Miyas’ everywhere only then they will leave Assam: Himanta Biswa Sarma
Says “Himanta Biswa Sarma, BJP are openly against them, we are saying it openly
New Delhi: Assam Chief Minister Himanta Biswa Sarma on Tuesday said that four to five lakh “Miya voters” would be removed from the electoral rolls in the state once the Special Intensive Revision (SIR) of voter lists is carried out. He also made a series of controversial remarks openly targeting the Miya community, a term commonly used in Assam in a derogatory sense to refer to Bengali-speaking Muslims.
Speaking to reporters on the sidelines of an official programme in Digboi in Tinsukia district, Sarma said it was his responsibility to create difficulties for the Miya community and claimed that both he and the BJP were “directly against Miyas”.
“Four to five lakh Miya votes will have to be deleted in Assam when the SIR happens,” Sarma said, adding that such voters “should ideally not be allowed to vote in Assam, but in Bangladesh”. He asserted that the government was ensuring that they would not be able to vote in the state.
The chief minister was responding to questions about notices issued to thousands of Bengali-speaking Muslims during the claims and objections phase of the ongoing Special Revision (SR) of electoral rolls in Assam. While the Election Commission is conducting SIR exercises in 12 states and Union Territories, Assam is currently undergoing an SR, which is usually meant for routine updates.
Calling the current SR “preliminary”, Sarma said that a full-fledged SIR in Assam would lead to large-scale deletion of Miya voters. He said he was unconcerned about criticism from opposition parties over the issue.
“Let the Congress abuse me as much as they want. My job is to make the Miya people suffer,” Sarma said. He claimed that complaints filed against members of the community were done on his instructions and that he had encouraged BJP workers to keep filing complaints.
“I have told people wherever possible they should fill Form 7 so that they have to run around a little and are troubled,” he said, adding that such actions were meant to send a message that “the Assamese people are still living”.
In remarks that drew further outrage, Sarma urged people to trouble members of the Miya community in everyday life, claiming that “only if they face troubles will they leave Assam”. He also accused the media of sympathising with the community and warned journalists against such coverage.
“So you all should also trouble, and you should not do news that sympathise with them. There will be love jihad in your own house.” He said.
The comments triggered reactions from opposition leaders. Raijor Dal president and MLA Akhil Gogoi said the people of Assam had not elected Sarma to keep one community under constant pressure. Congress leader Aman Wadud accused the chief minister of rendering the Constitution meaningless in the state, saying his remarks showed a complete disregard for constitutional values.
According to the draft electoral rolls published on December 27, Assam currently has 2.51 crore voters. Election officials said 4.78 lakh names were marked as deceased, 5.23 lakh as having shifted, and 53,619 duplicate entries were removed during the revision process. Authorities also claimed that verification had been completed for over 61 lakh households.
On January 25, six opposition parties the Congress, Raijor Dal, Assam Jatiya Parishad, CPI, CPI(M) and CPI(M-L) submitted a memorandum to the state’s chief electoral officer. They alleged widespread legal violations, political interference and selective targeting of genuine voters during the SR exercise, describing it as arbitrary, unlawful and unconstitutional.
