During his career, Franklin printed nearly 2,500,000 money notes for the American Colonies using what the researchers have identified as highly original techniques, as reported in a study published this week in the Proceedings of the National Academy of Sciences.

The research team, led by Khachatur Manukyan, an associate research professor in the Department of Physics and Astronomy, has spent the past seven years analyzing a trove of nearly 600 notes from the Colonial period, which is part of an extensive collection developed by the Hesburgh Libraries’ Rare Books and Special Collections. The Colonial notes span an 80-year period and include notes printed by Franklin’s network of printing shops and other printers, as well as a series of counterfeit notes.

Manukyan explained that the effort to print money for the fledgling Colonial monetary system was important to Franklin not just as a printer but as a statesman as well.

“Benjamin Franklin saw that the Colonies’ financial independence was necessary for their political independence. Most of the silver and gold coins brought to the British American colonies were rapidly drained away to pay for manufactured goods imported from abroad, leaving the Colonies without sufficient monetary supply to expand their economy,” Manukyan said.

However, one major problem stood in the way of efforts to print paper money: counterfeiting. When Franklin opened his printing house in 1728, paper money was a relatively new concept. Unlike gold and silver, paper money’s lack of intrinsic value meant it was constantly at risk of depreciating. There were no standardized bills in the Colonial period, leaving an opportunity for counterfeiters to pass off fake bills as real ones. In response, Franklin worked to embed a suite of security features that made his bills distinctive.

“To maintain the notes’ dependability, Franklin had to stay a step ahead of counterfeiters,” said Manukyan. “But the ledger where we know he recorded these printing decisions and methods has been lost to history. Using the techniques of physics, we have been able to restore, in part, some of what that record would have shown.”

Manukyan and his team employed cutting-edge spectroscopic and imaging instruments housed in the Nuclear Science Laboratory and four Notre Dame research core facilities: the Center for Environmental Science and Technology, the Integrated Imaging Facility, the Materials Characterization Facility and the Molecular Structure Facility. The tools enabled them to get a closer look than ever at the inks, paper and fibers that made Franklin’s bills distinctive and hard to replicate.

One of the most distinctive features they found was in Franklin’s pigments. Manukyan and his team determined the chemical elements used for each item in Notre Dame’s collection of Colonial notes. The counterfeits, they found, have distinctive high quantities of calcium and phosphorus, but these elements are found only in traces in the genuine bills.

Their analyses revealed that although Franklin used (and sold) “lamp black,” a pigment created by burning vegetable oils, for most printing, Franklin’s printed currency used a special black dye made from graphite found in rock. This pigment is also different from the “bone black” made from burned bone, which was favored both by counterfeiters and by those outside Franklin’s network of printing houses.

Another of Franklin’s innovations was in the paper itself. The invention of including tiny fibers in paper pulp — visible as pigmented squiggles within paper money — has often been credited to paper manufacturer Zenas Marshall Crane, who introduced this practice in 1844. But Manukyan and his team found evidence that Franklin was including colored silks in his paper much earlier.

The team also discovered that notes printed by Franklin’s network have a distinctive look due to the addition of a translucent material they identified as muscovite. The team determined that Franklin began adding muscovite to his papers and the size of this muscovite crystals in his paper increased over time. The team speculates that Franklin initially began adding muscovite to make the printed notes more durable but continued to add it when it proved to be a helpful deterrent to counterfeiters.

Manukyan said that it is unusual for a physics lab to work with rare and archival materials, and this posed special challenges.

“Few scientists are interested in working with materials like these. In some cases, these bills are one-of-a-kind. They must be handled with extreme care, and they cannot be damaged. Those are constraints that would turn many physicists off to a project like this,” he said.

But for him, the project is a testament to the value of interdisciplinary work.

“We were fortunate to have student researchers on this project with interests both in physics as well as in history and art conservation. And the core research facilities as well as the Rare Books and Special Collections team were incredible research partners. Without an uncommon level of collaboration across disciplines, our discoveries would not have been possible.”

How do these networks form and how are they maintained? For the long-lived macrophages (phagocytes), the answer is already known: They settle in so-called niches. These are environments of connective tissue cells that supply the macrophages with nutrients and keep them alive.

A team led by Professors Georg Gasteiger, Dominic Grün and Wolfgang Kastenmüller from the Institute of Systems Immunology at Julius-Maximilians-Universität Würzburg (JMU) / Max Planck Research Group has now turned its attention to a related type of immune cells, the so-called dendritic cells.

These immune cells are essential for the control of immune responses because they are at the first line of defense of the immune system: They recognize foreign structures, take them in and process them into a kind of mugshot. They then present the photo to other immune cells and trigger a specific immune response, for example against pathogens or cancer cells.

Dendritic cells migrate through the tissue

The special thing about dendritic cells: They only live for about a week and during this time they continuously migrate through the body’s tissues. “In this respect, it was clear that the classic niche concept would not work here” , says Wolfgang Kastenmüller.

The JMU team found a completely new concept for this, according to which three-dimensional cell networks can organize themselves: Dendritic cells orient themselves to the blood vessels and migrate one after the other along their outer wall – similar to children walking in single file. The blood vessels thus determine the three-dimensional arrangement of the cells.

Cytokines keep the cells together

“We wanted to understand how this process is regulated and how the cells manage to close gaps in their network,” explains Dr. Milas Ugur, a scientist in Professor Kastenmüller’s group. Closing such gaps is important because otherwise the immune defense no longer functions optimally.

As the JMU team reports in the journal Immunity, it is due to a locally acting cytokine, the FLT3 ligand, that the dendritic cells always stay close together during their developmental migration.

The cytokines are continuously and evenly produced locally and consumed by the dendritic cells. If there are gaps in the group, more cytokines are available for the isolated dendritic cells. This surplus speeds them up in their development and movement and helps them to reconnect with the group. When the cells have moved up, they have a little less cytokines available again due to competition from their neighbours. Accordingly, they slow down their developmental speed.

Of prognostic value for tumour diseases

These findings are for example important  for cancer therapy: dendritic cells have a high prognostic value for tumour diseases: The higher their abundance in the tumour, the better the prognosis for the patient. This is especially true after immunotherapy.

“Increasing our basic insights on dendritic cell biology will help us to restore the networks of these cells in tumours and thereby tailor optimal therapies in the future” explains Kastenmüller.

How the researchers are moving forward

The JMU researchers’ data so far is based on the analysis of lymph nodes from animal models. The team next wants to test whether the same principles of network organisation of dendritic cells apply to all tissues and also in humans.

The work described was done in cooperation with researchers from the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI) and with scientists from France and Japan.

“We know little about how the immune system develops throughout life, and most of what we know about immune system development in children comes from animal studies,” says Donna Farber, PhD, an expert in immune system development at Columbia University Vagelos College of Physicians and Surgeons who led the research. “But mice develop much more quickly than humans and their immune systems are a bit different than ours.”

Using a trove of tissue samples from deceased pediatric organ donors, Farber’s team was able to pinpoint aspects of immune system development that distinguish babies from adults.

Immune cells in lungs and gut take time to mature

One study, published in Immunity, found that specialized immune cells called memory T cells — formed after first exposure to a pathogen — accumulate rapidly in the lungs and intestines through age 3 and more gradually in blood and lymph tissues. These cells enable older children and adults to mount an immediate and specific immune response during the next encounter with a pathogen.

But there’s a hitch.

“We found that memory T cells in young children are not functionally mature and only begin to have the capacity for protective immunity at around ages 4 to 6 years,” Farber says. “This explains why babies and young children are more vulnerable to recurrent respiratory infections and other infectious diseases compared with adults.”

The findings also may explain why introducing foods to children during the first year of life could prevent severe food allergies. “Early memory T cells are more tolerant than mature memory cells, so they’re not going to create an immune response against new foods,” Farber says.

‘Secret weapon’ protects babies from new pathogens

But while babies are highly susceptible to recurrent infections, a second study, published in Nature Immunology, found that babies have a unique way of coping with new pathogens. The researchers found clusters of antibody-producing B cells surrounded by T cells in the infants’ lungs. This bronchus-associated lymphoid tissue, or BALT, is formed between 6 and 12 months of age and disappears after age 3.

“BALT enables the lung to make antibodies to respiratory pathogens well before T cell memory has developed but fall apart in later childhood when they are no longer needed,” says Farber. “This mechanism helps young children respond to the many different respiratory pathogens they encounter early in life.”

It also may explain why young kids are more resilient to new respiratory infections compared to adults — including SARS-CoV-2.

“With SARS-CoV-2, a virus no one had ever encountered before, we saw that people in their 50s and 60s were very susceptible to severe COVID, but most kids exposed to SARS-CoV-2 were fine, and many didn’t even have symptoms,” Farber says. “That told us that the babies and young children must have some adaptations to respond to new pathogens that adults don’t have.”

BALT also may be a reason why some children develop chronic asthma and allergies. “It’s possible that these diseases may be caused in part by the abnormal persistence of BALT well into childhood, which could trigger an overreaction to certain antigens,” says Farber.

Farber adds that the study may provide clues about why early trials of intranasal COVID vaccines have not shown promise in adults, whereas intranasal influenza vaccine tends to work better in children. “It could be that this type of vaccine works better in children because they have BALT structures that can initiate new antibodies in the lungs.”

“BALT provides some protection but clearly does not protect young children from everything,” Farber continues. “We have to remember that before vaccines, a third of children died of infectious diseases during infancy. So childhood vaccines are really important for protecting us.”