Accidental Adventures in Immunology

by Joan Harvey

As we’ve all noticed, as soon you mention something about, say, your neighbor’s annoying poodle and your phone is anywhere within a three mile radius, you immediately get ads for poodles, poodle accessories, poodle food, and yet more poodles. I must have been talking or writing to someone about my immune issues, or possibly just Covid, and boom, they got me. Among all the ads I get for sheer underwear with snakes on it, there it was: immunology, Coursera, first week free, then $49 a month. Okay, I thought, I should know something about this, I’ll sign up, learn a bit, and go on my merry way. Little did I know. Because I’m someone who often doesn’t pay attention to details—exactly the wrong type for this sort of thing—I accidentally ended up in a course from Rice University designed for people with a serious interest and commitment to actually knowing how antibodies work.

I’m not much for video learning in general, or at least I hadn’t been until Covid, when a friend pointed out to me that the wonderful British-Israeli cookbook writer Yotam Ottolenghi did a Master Class. Up until that point I had conscientiously avoided Master Class and all those celebrities telling you they have the answer to life and if you just follow their advice you are guaranteed to become a confident-glamorous-successful novelist-filmmaker-model-architect. I’d also never had a cooking lesson, and found Ottolenghi’s cookbooks (of which I have four) intimidating, though when I attempted one of his recipes, or, more usually, part of one, it was always delicious. I would not have considered learning cooking from anyone else, but Ottolenghi was irresistible. So I paid the fee and there he was in my kitchen: relaxed, gay, handsome, with his wonderful accent, pouring olive oil on everything, squeezing lemons with his hands, squooshing garlic, talking me through each step, making everything easier. With him nearby I was no longer the anxious cook I often am; I was relaxed and reassured, and, following his steps, the food I turned out—Smacked Cucumber Salad with Sumac-Pickled Onions, Mafalda Pasta with Quick Shatta, Pea Spread with Smoky Marinated Feta—was actually amazing. I was only sorry there weren’t more recipes. But that was the extent of the video learning I’d done until my venture into B-cell arcana.

Because of that fatal Coursera ad, instead of baking wonderful delicious-smelling loaves of bread, as sensible people did during the pandemic, I took up science. It didn’t start out too badly, in part because I had no idea what I’d gotten myself into. But slowly it dawned on me: this was an intermediate course and my knowledge of biology was limited to one college semester decades ago. Back then I had decided biology was not for me when we had to count Drosophila eyes. Genetics. And, guess what? Immunology has a lot to do with genes.

As I began to work my way through the six weeks of Fundamentals of Immunology: Innate Immunity and B-Cell Function, I was somewhat ambivalent: should I be spending this much time and devoting my very limited brain power to something way beyond my skill set and actually pretty useless to my everyday life? The downside of learning immunology, if you are a regular citizen, is that, no matter how much you learn about antibodies and antigens and RNA transcription, it will have no impact on your ability to fix your immune system—unlike, say, wiring a house, where with some study, even if you aren’t a specialist, you can actually do something to change your environment for the better (unless you get electrocuted in the process).

For some reason Coursera had me listed as a software designer, an occupation even farther from my range of abilities than biology. But, as I enjoy being someone quite other than I am, I let it stand. Even as a software designer, however, I felt unequipped to face the nine or ten video sections with nine or ten practice quizzes plus a regular quiz each week, with a final exam at the end of it all. And, my plan to dip in and rapidly dip out was confused by the fact that if I did so, I would flunk. Suddenly I was on the proverbial horns of a dilemma. It would make absolutely no difference to my life if I passed or failed, and yet the thought of getting a bad grade didn’t suit my (very scientifically delineated) superego. So here I was, not knowing half the language or concepts that someone with a more recent basic biology course would have down pat, and either I had to concentrate, or, damn it, fail. So on I went. I gave the course enough attention to do well on the quizzes, but not always to understand things as deeply as I knew I should. I’ve always been good at tests, which on my case is actually a bad thing in terms of solid knowledge. I can get a right answer, without actually understanding what in hell is really going on.

Still, I figured that as I wasn’t going on to any kind of medical work, it would do no poor victim any harm if my understanding was subpar. Fortunately the professor was a tremendously engaging woman with the wonderful name of Alma Moon Novotny, who demonstrated things with models and drawings and obviously knew her stuff backwards and forwards. She spoke of immunology as “development in a foreign language,” and talked about metaphor, more familiar ground for me. She also compared the defense of the body with the defense of the country and said if you don’t put enough effort into it, “a country can end up overrun by Nazis.”

I know from my medical history that my B-cells don’t all mature properly (I’m immature even at the cellular level). I’d also seen blood test results involving light chains and heavy chains, a concept meaningless to me until this course. B-cells, it turns out, are named for the place they were discovered, the Bursa of Fabricius, an organ only found in birds. Fortunately in humans B-cells are formed in the bone marrow, so the B can stand for either bursa or bone. T-cells come from the thymus. Antibodies, I learned, are typically composed of two immunoglobulin heavy chains and two immunoglobulin light chains. This was just the beginning, but already more than I’d learned from years of seeing an immunologist and getting back strange test results. Of course these more basic things were by far the easiest part of the class. My sister told me there’s a joke about immunology, but…it’s complicated.

Already in the very first lecture, a term taken for granted by Novotny and therefore not discussed, hematopoeisis, was one I didn’t know. I supposed it was basic biology, and not that hard to figure out, as I knew hematologists were experts in blood. I looked it up; the hema part was from the Greek for blood and the poiesis from the Greek “to make,” and it referred to the formation of different blood cells derived from stem cells. All those neutrophils and eosinophils and the rest, including of course, the B-cells. The numbers are astonishing: 1011 to 1012 cells produced daily. Although the term hematopoesis was taken for granted in the course and never discussed, it was interesting to me to think of our blood in terms of this prodigious making, this daily bringing into being constantly going on inside us. I found it hard not to connect poeisis with poetics, and from there to think of the poetry of our mysterious bodies. This bringing into presence.

My sister, who did study biology, said her favorite word from immunology is pluripotent. Pluripotent stem cells can give rise to all of the types of cells in the body. All those possibilities! How much better to be pluripotent than omnipotent. Another word I learned and liked was Ikaros, a transcription factor needed for B-cell development and function. Ikaros, I learned online, though not in the course, is part of a family of proteins, which include Aiolos, Helios, Eos, and Pegasus. On the most basic level our bodies are knotted up with Greek mythology. And though Novotny did her best with excellent models of antibodies, and even cartoons—the sentinel dendritic cells, for instance, were depicted as eager little scouts—she still had to describe the models in language, just as we use the letters of the alphabet for the genetic code. Turns out the Greeks pretty much own our language for both the invaders and the defense. For example, I learned recently from Stephen Fry’s book Mythos that staph, an infection I’ve had plenty of times, though fortunately not in any dangerous way, comes from staphylo, meaning like a bunch of grapes, so named because under the microscope the spherical Staphylococcus bacteria appear in grape-like clusters. It turns out Staphylus was originally the beloved of Dionysius, hence the grape thing. I’m pretty sure, though, that the great god of wine would not be happy about using his lover’s name in our current association.

The B-cell course was six weeks long, and at the beginning of week five I decided I was so out of my depth (all that complicated gene rearrangement and splicing and transcription) that I didn’t have the energy to continue. I was in unfamiliar territory, there was much to memorize, and I knew I’d never learn or understand it very well. And yet, there it was, that damned responsible student inhabiting me, telling me if I didn’t continue I’d have to live with the shame of failure. Somehow that was not acceptable. Turns out this is genetic as well: my grandmother, in an interview about being analyzed in the late 1920s, said, “I was on the point of stopping many, many times, and I think it’s only because I had a very persistent and determined character and seldom stopped anything that I had begun but I did continue, but I was often wanting to stop.” So, like her (damn you genetics), I grudgingly kept going. I made the deadlines, I passed the quizzes, and I did well on the final (after I took it a second time). The really ridiculous thing was that I was tempted to continue on to the next class on T-cells. But, fortunately, even I am not that dumb.

It’s appropriate, given that what I understood of immunology was mostly through language (though I do have fond memories of the homemade antibody model that was used so often), that Alma Moon Novotny told us at the end, “Medical schools have said on the average, they increase the vocabulary of the typical medical student by 30,000 words. . . [T]hey don’t really increase it that many, it’s just that at the end of your first year in medical school you have or are supposed to have a 30,000-word medical vocabulary.” My medical vocabulary was pretty much non-existent at the beginning of the course, but I now know a few more words. I know a little something about how antibodies work. I understand much better why, for example, the vaccine takes some time before it is effective. I now know better how memory B-cells work and how T-cells interact with them. I learned that the monoclonal antibodies that are produced in labs end in ab, so now the drug Rituximab, one that has been suggested I might possibly try in the future, is less mysterious. I know something about immunoglobulin receptors and G-class antibodies and lymphoid progenitors and recombination signal sequences. Do I understand any of this very clearly? Not nearly as clearly as I should, considering. But a little window has opened onto something going on constantly inside me, and into my not altogether efficient immune system, and this is pleasing to me.

But damn you, Internet. Think of all the tasty loaves of bread I could have baked in that time.