Tailor made

When I was 19, I was a model for the “dress and suit” class at Rud Vocational School. The students had to learn how to sew a suit. I chose bottle green wool for a jacket with rounded edges and a pleated skirt. It was based on a standard pattern, and I tried on the suit several times along the way to ensure it would fit my body perfectly. This is exactly the case with our antibodies as well.

Few genes, many combinations

The B-cells of the immune system produce antibodies against invading microbes. Antibodies are made by combining a few specific gene motifs in many different ways. They are made following the same pattern, although there are variations in the specific design of each individual antibody. Just like how I got a suit with the possibility for variation within a given framework.

The first time a microbe binds to the B-cell receptor, the receptor usually does not fit perfectly with the microbe. However, the B cell will still be stimulated to divide and start producing antibodies, i.e. receptors that can be released from the cell into the blood.

Random changes

A B cell that is stimulated to divide will first become two cells, then four, eight, and so on. These daughter cells will also have B-cell receptors that can bind to microbes.

However, in the daughter cells, random changes will occur in the B-cell receptor gene. As a result, all the daughter cells will have B-cell receptors that are slightly different from the original B cell. This phenomenon is called “somatic hypermutation“. It is similar to the times when I tried on the suit before it was finished, with small changes being made each time.

Darwin in the body

As long as the microbe is present, the new B cells will also bind to the microbe. If the altered receptor fits the microbe better, the B cell will receive a signal to continue dividing.

If, on the other hand, the receptor is a poorer fit, the B cell will not receive any signal and will soon be outcompeted by B cells with receptors that are better suited to the microbe. This is Darwinian evolution.

In this way, antibodies against a microbe become a combination of ready-to-wear and tailoring.

Repeated adjustment when needed

I still have the bottle green suit. After more than forty years, it still fits, if no longer perfectly. Although I weigh the same as before, the jacket has clearly become tighter around the shoulders. The body has simply changed a bit. Unfortunately, there is nothing I can do about my body, and I am unlikely to make any adjustments to the suit either.

For B cells, it’s different. After the initial encounter with a microbe, some B cells with receptors tailored for that microbe will remain in the body for several decades.

During the next encounter with the microbe, perhaps many years later, the microbe might have changed a bit, becoming slightly “broader around the shoulders.” In that case, the B cells will be stimulated again to divide and activate the “change machinery” for their B cell receptors.

And unlike my bottle green tailored suit that can no longer be altered, we will once again have antibodies that fit perfectly to the microbe as it is right here and now.

Blog post by Anne Spurkland, first published in Norwegian in 28 October 2012, translated to English 23 January 2024.

Born that way or become that way

Two days ago, I cut my finger while slicing apples. This required urgent fingertip bandaging so there wasn’t too much mess while I finished the apples. But the cut was not dangerous or life-threatening in any way. It’s because I was born that way. When I don’t tend to get sick with the flu either, it’s because I’ve become like that.

Immunologists divide the immune system into innate and adaptive. We take the innate for granted. We consider it obvious that a cut in the finger will heal itself in about 4-5 days. The innate immune system, which includes things like the macrophages, is so effective that it’s only very recently that scientists have begun to gain detailed insight into how it works. The innate immune system is largely the same in all people.

The adaptive immune system, on the other hand, is tailored to me and to the environment I have lived in. This part of the immune system includes T and B cells. It is the adaptive immune system that prevents me from getting the flu, chickenpox, measles, and many other infectious diseases that I have had earlier in life or that I have been vaccinated against. When doctors try to understand why we get sick from infections, or why someone suffer from chronic inflammatory diseases, it has traditionally been the adaptive immune system that has been in focus. This is probably why we have the most knowledge about how this part of the immune system works.

For long, immunologists thought of the innate and the adaptive immune systems as two separate entities that had little to do with each other. Now we know there is a lot of cross-talk and even tight connections between the two parts of the immune system. To use my finger as an example:

When I cut my finger, bacteria will immediately enter the wound. The injury itself, as well as the bacteria, will trigger an inflammatory response. The bacteria will be engulfed by macrophages, which also summon other parts of the innate immune system to the site of injury. In most cases, this is enough to remove the bacteria and repair the damage. If the bacteria are too numerous or they are particularly aggressive, the innate immune system needs help from the adaptive immune system. Antigen-presenting cells from the innate immune system will stimulate T-helper cells so that an immune response adapted to the specific microbe is initiated. This is why a bacterial infection following a cut in the finger will almost always be contained at the site of injury and will heal within a few days.

Blog post by Anne Spurkland, written 25.10.12. Last updated and translated to English on 20th January 2024

Baccalao

In 2011, Norwegian researchers published in Nature, one of the world’s most prestigious journals, a map of the cod’s genes. The cod is “ours”. For centuries it has given livelihood for people along the entire Norwegian coastline, including my own grandfather that exported salted, dried cod to Portugal and Brazil. It was therefore a big surprise when the researchers discovered that the cod lacks genes for HLA class II molecules.

Pomander balls

One of the cosiest things I like to do before Christmas is to make pomander balls. Their smell of cloves and orange is so pleasant. They are easy to make, also for those with less well-developed fine motor skills. In addition, the orange balls with brown dots looks lovely, hanging in the window frame. In fact, they have some resemblance to virus particles.

With lisence to kill

The next movie about James Bond, the hero with lisence to kill, will be the 27th film in the series. Immunologists don’t need to wait several years between each time we get to see and hear new stories about secret agents with lisence to kill. We’ve got the killer T-cells.

Cream cake or cream cake?

Recipes for cream cakes often go down through Norwegian families. The exact combination of filling and decoration can vary substantially from family to family. But no one is ever in doubt that the result is cream cake, nor that the cake looks yummy.

Funnel chanterelle

I love picking mushrooms, especially funnel chanterelles. They are small, brown and easy to recognize on their yellow, slightly angular stem, which is hollow from the hat down to the root. In addition the gills under the cap extends down the stem. Yet, in recent years I have become more careful when I pick and clean the funnel chanterelles.

Granma’s cream puff

I was 13 when my grandma taught me how to bake cream puffs. Puffs are these round, hollow and slightly crispy pastries that can be filled with cream. I was an eager teenager housewife and she was an experienced baker. Nevertheless, the first round of puffs turned out a failure. The puffs did not rise, the dough had been too hot. That day I learned that some recipes must be followed to the letter, else it will not work.

The groove

When my boyfriend finally returned from Africa in 1989, two years of intense letter writing came to an end. I had written about my life as a budding researcher, he about his life as a volunteer in the bush. Still I became a bit puzzled the morning of our reunion in Paris, when he after a night in a cheap hotel bed announced that he had dreamt that we were competing peptides in the HLA groove!

Dulce de leche “Hapå”

Although I am an omnivore, I must have dairy butter on my morning sandwich, otherwise I lose my appetite. Similarly, the Norwegian dulce de leche type spread “Hapå” is according the Nestlé advertisment an effective means to get the kids to eat their sandwiches.

The macrophages behave a bit in the same way. They eat everything, but it helps a lot if a bacterium is covered with “Hapå”. It then goes down a lot faster.