I always love the partly rushed, partly excited, and fully unwritten feeling of September. A new year has arrived, full of new beginnings and possibilities. Working at the university hospital in Amsterdam, September also means that the grounds are flooded with new students, and departmental seminars – complete with research talks from the other PhD students and post-docs – start up again. All this hustle and bustle around the start of the school year got me thinking about how the immune system was trained. And, as luck would have it, today's topic at my department's seminar centered on one of the most important teachers in the immune system: follicular dendritic cells! Today, we'll kick off the new school year of Microbial Mondays with a story about these immunological teachers. Here we go!
So– follicular dendritic cells (FDCs for short). Long name, but very important function. These cells hang out in places like your lymph nodes (like your tonsils), which are tissues largely dedicated to fighting infections. These cells look pretty darn striking. They have small cell bodies in the center, from which sprout long, filigree-like tentacles (scientifically termed dendrites) which spread out like a net around the tissue, almost like microscopic octopi sending out their feelers. These long tentacles help them do one of their major jobs: trapping antigen.
As we've talked about before on Microbial Mondays, "antigen" is more or less an immunologist's term for a molecule that has entered somewhere it doesn't belong. This can include little pieces of bacteria, fungus, or virus, or a chunk of parasite, or even bits of your own body that have leaked out where they shouldn't. All these little bits and pieces are caught by the tentacled FDCs.
At one level, the FDCs then simply function as a sort of stringy storage facility. As you might remember from the post on vaccines, antigens are part of the language of the immune system. It's these tiny bits and pieces of "stuff that shouldn't be there" that train your immune system to recognize and attack the full-blown, actually harmful versions microbes that are floating around in your system. The FDCs hold on to lots of these antigens, and hold on to them for long enough that the immune cells that will later attack those bad bugs can learn to recognize the bits and pieces. You can think of this system sort of like the third grade teacher who made you repeat your times tables over and over again. Every day, you'd go back and repeat again, "6x4=24. 11x9=99. 9x7=63....." and so on, until the end of time, or so it felt to your third grade self. The attack cells in your immune system do basically the same thing: they come back again and again to the FDCs to visit the same antigens until they've learned to remember them correctly.
On top of training the attack cells, FDCs also encourage the attack cells to keep at it. As the attack cells are training, FDCs send out signals saying, "Keep going! You can do it! Stay alive! Live long and prosper!" These interactions of training and encouragement between the FDCs and attack cells are actually central to the functioning of vaccines. By both showing cells what they need to look for, and giving them pep talks to keep them alive, FDCs help create "immunological memory".
That's right, your immune system has a memory too. Of course, your immune system doesn't have its own brain to remember past pathogens ("bad bugs"). However, there are still specific cells in your immune system that are responsible for maintaining this memory. These are long-lived cells that can divide into lots of attack cells that will dive into action and wage a war against any pathogens displaying antigens that they recognize. The main benefit of having a memory for pathogens is that it takes a lot less time to battle an enemy that you know and remember, versus one that you don't know or have forgotten. For instance, if you know that your foe only fights with gossip and snide comments, you don't have to waste energy learning karate to combat him or her. Your immune system prefers to be efficient; fighting is exhausting, after all.
Creating this immunological memory is also the main goal of vaccines. A vaccine is pretty much just a shot of bits and pieces of the microbe you want to protect against. Nowadays, because we know that FDCs are so important to immunological memory, it's pretty well accepted that to make a good vaccine, you want to get those antigens to those tentacles. That's where the magic can happen. Once the vaccine antigens are picked up by the FCDs, they can drill the memory of the antigens into your immune cells just like your elementary school teachers drilled the memory of the times tables into you.
With that, I'll leave you with a challenge. Can you still do your times tables?
Happy back to school!
~Alex
For more in-depth reading, these are the papers this blog post is based on. The departmental talk that helped inspire this article was given by Dr. Heesters, the first author of reference #1.