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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Russian President Putin says India, Russia collaboration not directed against anyone
New Delhi (PTI): The India-Russia collaboration is not directed against any country and it is solely aimed at safeguarding the national interests of the two sides, Russian President Vladimir Putin has said against the backdrop of Washington's aggressive approach towards New Delhi and Moscow.
In the context of India's energy ties with Russia, Putin said certain "actors" dislike New Delhi's growing role in international markets in view of its close relations with Moscow and these elements are aiming to constrain India's influence for political reasons by imposing "artificial obstacles".
In an interview to India Today news channel that was released on Thursday evening, the Russian president, referring to Western sanctions against Moscow, said his country's energy cooperation with New Delhi largely "remains unaffected".
Putin landed in New Delhi this evening on a two-day visit to hold summit talks with Prime Minister Narendra Modi.
ALSO READ: PM Modi presents copy of Gita in Russian to Putin
His trip comes at a time India-US relations are going through possibly the worst phase in the last two decades after Washington imposed a whopping 50 per cent tariff on Indian goods, including 25 per cent levies for New Delhi's procurement of Russian crude oil.
"Neither me nor Prime Minister Modi, despite certain external pressure we face, have never approached our collaboration to work against someone," the Russian president said in response to a question on Washington's aggressive approach.
"President Trump has his own agenda, his own goals, whereas we focus on ours -- not against anyone, but rather aimed at safeguarding our respective interests, India's and Russia's interests," he said.
Rejecting Washington's objection to India procuring crude oil from Russia, Putin said if the US has the right to buy Russian fuel, why "shouldn't India have the same privilege".
"As for India's purchase of energy resources from Russia, I would like to note and have already mentioned this once, the US itself still buys nuclear fuel from us for its own nuclear power plants," Putin said.
The Russian president also responded to a question on India lowering procurement of crude oil from Russia in view of Western sanctions on Moscow.
ALSO READ: Russian president Putin arrives in Delhi on 2-day visit
"Well, there is a certain decline in overall trade turnover during the first nine months of this year. This is just a minor adjustment. Overall, our trade turnover stands almost at the same level as before," he said.
"I can't give you exact monthly figures right now, but trade in petroleum products and crude oil, as well as the production of petroleum products for consumers of oil, Russian oil, is running smoothly in India," he said.
Putin also said that India cannot be treated the way it was several decades back.
"Prime Minister Modi is not someone who succumbs to pressure easily. The Indian people can certainly take pride in their leader. This is absolutely obvious," he said.
"His stance is unwavering and straightforward, without being confrontational. Our goal is not to provoke conflict; rather, we aim to protect our lawful rights. India does the same," he said.
On the Ukraine conflict, Putin said he believed the US is actively seeking a solution to this problem. "I am absolutely certain, with no doubt at all, he (Trump) sincerely aims for a peaceful resolution."
Putin said Trump genuinely wants to end the hostilities and prevent further loss of lives. "But there could also be political interests tied to ending the confrontation between Russia and Ukraine, or economic motives too."
On bilateral trade, Putin said over 90 per cent of "our transactions are already conducted in national currencies".
"While some complications arise due to the presence of numerous intermediaries, there are also solutions," he said.
The Russian president also complimented PM Modi's leadership.
"Our collaborative endeavours with Prime Minister Modi carry significant weight because they transcend our mutual ties," he said.
"Given its direct relevance to both nations, ensuring stability in key areas of engagement is crucial, as it helps secure the fulfilment of our objectives. Prime Minister Modi sets very challenging tasks for the country --and for himself in the first place, then for the administration, and eventually for the nation," he said.
The Russian president did not give a direct reply to a question on if India was looking at procuring additional batches of S-400 missile systems.
"India stands out as one of our reliable and privileged partners in this area. We are not merely selling something to India and India isn't merely buying something from us in the sphere of defence and security.
"It is a different level, a different quality of relations we have with India, and we value this. We see how India values this relationship too," he said.
Putin said Russia is not simply selling defence technology to India but it is sharing it with the country.
"It is a very rare thing to see in the sphere of military-technical cooperation. It speaks to the level of trust between the two countries and the level of trust between the two peoples.
"We have a broad portfolio indeed, including naval construction, rocket and missile engineering, and aircraft engineering," he added.
