Run the first half of a marathon as fast as you can and you’ll likely never finish the race. Run an engine at top speed for too long and you’ll burn it out.
The same principle seems to apply to our T cells, which power the immune system’s battle with chronic infections like HIV and hepatitis B, as well as cancer. Too often, they succumb to “T cell exhaustion” and lose their capacity to attack infected or malignant cells. But could T cells learn to pace themselves and run the full marathon?
That’s the thinking behind a research study published last week by TheJournal of Experimental Medicine. “Our research provides a clear explanation for why T cells lose their fighting ability,” says Florian Winau, MD, “and describes the countervailing process that protects their effectiveness.” …
At the dawn of his career, immunologist, biological chemist, molecular pharmacologist and seven-time biomedical entrepreneur Timothy Springer thought science was a bad idea. “I was suspect of the purposes that science had been put to,” he says, “making Agent Orange and napalm.”
It was 1966, and Springer was a Yale undergrad thinking, “What the hell good is this Ivy League education? The best and brightest, the Ivy League-educated people, totally screwed up in getting us into the Vietnam War.”
So he dropped out. For a year, he lived on a Native American reservation in Nevada for Volunteers in Service to America (VISTA). He helped the Tribal Council draft resolutions, launched a 4-H club and lobbied for paved roads so kids could go to school.
Finally, he returned to school at the University of California, Berkeley — trying anthropology, sociology and psychology. Switching to biochemistry his junior year, Springer asked his advisor, scientific visionary Daniel Koshland, Jr., former editor of Science, “Do you think I can do this — graduate with a degree in biochemistry?” …
Bacterial infections that don’t respond to antibiotics are of rising concern. And so is sepsis — the immune system’s last-ditch, failed attack on infection that ends up being lethal itself. Sepsis is the largest killer of newborns and children worldwide and, in the U.S. alone, kills a quarter of a million people each year. Like antibiotic-resistant infections, it has no good treatment.
As organs go, the brain seems to harbor an abundance of somatic mutations — genetic variants that arise after conception and affect only some of our neurons. In a recent study in Science, researchers found about 1,500 variants in each of neurons they sampled.
New research revealing the propensity of DNA to break in certain spots backs up the idea of a genetically diverse brain. Reported in Cell last month, it also suggests a new avenue for thinking about brain development, brain tumors and neurodevelopmental/psychiatric diseases. …
A deep genetic analysis, involving nearly 65,000 people, finds a surprising risk factor for schizophrenia: variation in an immune molecule best known for its role in containing infection, known as complement component 4 or C4.
The findings, published this week in Nature, also support the emerging idea that schizophrenia is a disease of synaptic pruning, and could lead to much-needed new approaches to this elusive, devastating illness. …
The saying in the design world is that form follows function. But in biology, and protein biology in particular, it would be more correct to say that form begets function. Shape and structure are the foundation for most protein-based interactions in cells, and are why basic functions like receptor binding, antibody neutralization and gene transcription work.
Two enzymes in the immune system’s B cells, called RAG1 and RAG2, are a perfect example. Together, they form a complex that splices antibody-producing genes together in unique combinations through a process called V(D)J recombination. They do a similar job in T cells to build antigen-binding T-cell receptors (TCRs). In either case, the enzymes are essential to a robust immune response.
Why don’t these wounds close? Blame a perfect storm of diabetic complications, such as reduced blood flow, neuropathy and impaired signaling between cells. According to research by Denisa Wagner, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, a poorly understood feature of our immune system’s neutrophils may be one more ingredient in the storm.
If you follow cancer biology, then you’ve probably heard of ubiquitin before. Ubiquitin tags a cell’s damaged or used proteins and guides them to a cellular machine called the proteasome, which breaks them down and recycles their amino acids. Proteasome-blocking drugs like Velcade® that go after that recycling pathway in cancer cells have been very successful at treating two blood cancers—multiple myeloma and mantle cell lymphoma—and may hold promise for other cancers as well.
Less well known, however, is the fact that ubiquitin helps normal, healthy cells raise an alarm when viruses attack. Ubiquitin works with a protein called RIG-I, part of a complex signaling pathway that detects viral RNA and triggers an innate antiviral immune response.
Immune system cells called neutrophils sometimes do much the same: When confronted with bacteria, they unravel and shoot out their chromatin—the tightly wound mix of DNA and proteins that keeps genes packaged in cells. The resulting molecular mesh, known as a neutrophil extracellular trap, or NET, traps and kills bacteria, providing an additional line of defense against bloodstream infections.