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.
Yes, Strep causes sore throats but there are many types of Strep. Strep is short for Streptococcus which is the genus of the family. And then there are many species of Streptococcus. In fact, there are so many species in the family tree they are in groups from “A” to “H”. Streptococcus pyogenes is the specific organism that causes “Strep throat” but it also causes impetigo. Streptococcus pneumonia causes ear, sinus, bronchial and lung infections. Streptococcus faecalis causes urinary infections.
But the Strep that I think you heard about is Streptococcus salivarius. As the “species” name implies this is actually part of the normal microbiome in our saliva, in our mouths. However, when it jumps borders and colonizes the nose and sinuses it can cause mischief. Researchers at the NIH found that patients with allergic rhinitis who also had the Strep salivarius in their nasal membranes had worsening of their underlying allergies. Getting rid of the Strep salivarius led to significant improvement in their allergic rhinitis. It seems that when the Strep salivarius resides in the nose (but not when only in the mouth) it produces inflammatory proteins that work synergistically with the inflammatory mediators produced by allergy. The end result is a “double whammy”. The NIH is researching a bacterial selective treatment that will only remove the nasal Strep and not affect the rest of the microbiome. Stay tuned.
The New England Journal of Medicine recently published a research article on a drug trial of difelikefalin (who comes up with these names?) to treat Notalgia paresthetica. Notalgia paresthetica is an allergic mimic; it is actually a form of localized neuropathy. It is sometimes called the itch that rashes. It is characterized by chronic recurrent localized itching (usually unilateral) in the interscapular paravertebral area. (i.e., the shoulder blade).
It is felt to be due to dysfunction of the cutaneous branches of thoracic spinal nerves. Because the itch is so intense it leads to excessive scratching which in turn leads to the skin both thickening and darkening. It is resistant to therapies such as antihistamines and topical anti-itch creams and topical steroid creams.
Difelikefalin is a selective kappa opioid receptor agonist. It has been known for many years that the sense of itch is carried in our sensory pain fibers. Think back to a skin injury or cut that was painful at the onset but itched as it was healing. Opioids of all forms have been used to treat pain. The selective kappa receptor on pain fibers has been shown to suppress itch when it is stimulated. Hence the development of Difelikefalin.
The drug study had a small enrollment (126 people) but the 8-week trial showed excellent results. The main side effects were nausea and constipation. A larger study is underway to try and obtain FDA approval.
True or classic drug allergy is mediated by the drug activating the allergic protein (IgE) which in turn causes Mast cells in the skin and throughout the body to release histamine. However, it has been known for quite some time that some drug reactions are not mediated by IgE. These have been referred to as pseudo-allergic reactions or anaphylactoid (as opposed to anaphylaxis).
Then comes the discovery of Mas-related G protein – coupled receptor X2 (MRGPRX2) which sits on the surface of Mast cells (primarily Mast cells in the skin). When this receptor is stimulated it too causes Mast cells to release histamine. The most common drugs that do this are: Leupron, Firazyr, Cetrotide, neuromuscular blocking agents (used in anesthesia), opiates, fluoroquinolones and vancomycin.
The one good thing about MRGPRX2 receptor is it is “low-affinity” i.e., it requires a high concentration of drug to be activated. This is in contrast to the IgE receptor which is high affinity. A practical example is opiate. If the dose is kept low enough many people can tolerate these drugs without reaction.
A recent article in the Proceedings of the National Academy of Sciences discussed the discovery of a bacteria whose only diet is viruses; hence the name virovore. Actually, the scientific one is Halteria ciliate.
These bacteria were first discovered in fresh water ponds. In the lab, each Halteria organism consumed 1 million viruses daily, but when studied in their natural element they consumed 1 quadrillion viruses daily. Since Halteria do not seem to be pathogenic to humans there is ongoing research to see if there might be a way to use Halteria as a treatment for human viral infections.
Both the cause and treatment of Alzheimer’s are elusive. Current treatments are modestly effective at best. Recently touted to be the god-send treatment by removing the amyloid plaque the monoclonal therapy (aducanumab and lecanemab) has been a disappointment.
In fact, their failure has led to a shift in focus from the amyloid as the prime culprit to mitochondria. Yes, amyloid deposits are found in the Alzheimer’s brain but so too is found a reduction in mitochondria. Mitochondria are the powerhouse of neuronal cells (actually all human cells). Mitochondria generate the glucose that allows optimal neuron activity and reducing its availability impacts cognition.
But, another factor in the existing mitochondria in Alzheimer’s patients is they have a reduced mitochondria-associated membrane (MAM) electrical function. Excuse the pun, but current theory for our cognition is the electrical field generated by MAM in our brain cells. MAMs are the gatekeepers for ion flux which generates the electrical field. Reduced electrical field leads to neuronal degeneration and loss of cognition.
As tempting as it is to let nature turn your yellow car back to its original color, gentle precipitation is not only not strong enough to physically remove those tiny pollen specks, but water can actually activate or intensify its acidity! Soapy water however, binds to and neutralizes its pain damaging potential.
Oh boy kids! Guess what you get to do today!?!