The Immune System in a Nutshell
Or, a brief intro to this dauntingly complex yet fascinating system that keeps us alive
👋 Hey there! Welcome to a new edition of The Sunday Wisdom! My name is Abhishek. I read a lot of books, think a lot of things, and this is where I dump my notes and (so called) learnings.
I mostly write to educate myself; this is kind of my Feynman Technique in action. But if you like my writing, I would say this little hobby of mine just became a bit more purposeful. Now… time for the mandatory plug!
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Alright! Enough talk. On to this week’s essay.
After learning about the economic system for the past couple of weeks, let’s learn about another equally important and much much more complex system. But, unlike the previous one, this one wasn’t created by humans.
The key ideas are from Philipp Dettmer’s highly accessible and highly enjoyable book, Immune. This essay is in no way a replacement or a summary of the book. If at all, the purpose of this essay is to get you excited to learn more and in fact read the whole book. It’s about 2,200 words; this essay, not the book silly. Let’s go!
Q: What even is the immune system and how does it actually work?
Imagine waking up tomorrow, feeling a bit under the weather. There’s an annoying pain in your throat, your nose is runny, and you are coughing a bit. All in all, even though this is not bad enough to skip work. But as you step into the shower, you are pretty annoyed about how hard your life is at this moment.
While you are busy complaining and being a whiny little baby, your immune system is hard at work instead, without complaining. It’s busy keeping you alive so you can live to whine another day.
So, while intruders roam your body, killing hundreds of thousands of your cells, your immune system is organising complex defences, communicating over vast distances, activating intricate defence networks, and dishing out a swift death to millions, if not billions, of enemies. All while you are standing in the shower, mildly annoyed.
But this complexity is largely hidden.
For most of us, the immune system is a vague and cloud-like entity that follows strange and untransparent rules, and which seems to sometimes work and sometimes not. It is a bit like the stock market — extremely hard to predict and subject to endless speculations and opinions, resulting in actions that feel random to us.
(Unfortunately many people speak about the immune system with confidence (just like they do about the stock market) without actually understanding it. It can be very hard to know which information to trust and why.)
So, the central question that we are trying to answer is this: what even is the immune system, and how does it actually work?
Let’s crack on!
See, the primary job of the immune system is to defend your body against infectious agents such as viruses, bacteria, fungi, and parasites. This sounds simple enough, but this process is dauntingly complex.
For one thing, the immune system must tell the difference between cells that are normal parts of the body and cells that are invaders — in immunologic jargon, the immune system must be apt at distinguishing between self and non-self.
Somehow, the immune system can remember what every, and I mean every, cell in your body looks like, and any cell that lacks your distinctive cellular signature (for example, the cell of a bacteria) is considered an intruder and attacked.
But it isn’t that straightforward. For example, in the case of gut bacteria, the immune system recognises them as part of the normal flora that is beneficial for digestion and maintaining gut health. Therefore, it has developed mechanisms to differentiate between the harmless bacteria and harmful pathogens and only attack the latter.
On top of that, after your immune system encounters a novel invader, it also forms an immunologic memory of what the infectious agent looks like, to better prepare for future invasions — a process that is exploited when you are vaccinated with a mild version of an infectious agent in order to prime your immune system for a real attack later. Fascinating!
Now, let’s get into a bit of biology.
Immune defences are brought about by a complex array of circulating cells such as lymphocytes and monocytes. Cyte is a term for cells, and you might know the umbrella category of lymphocytes and monocytes (and various other cytes) as white blood cells or WBCs.
So, there are two classes of lymphocytes: T-cells and B-cells. Both originate in the bone marrow, but while T-cells migrate to mature in a gland (located in the chest region) called thymus (hence the T), B-cells mature in the bone marrow itself. They are too lazy to move.
B-cells produce a kind of protein called antibodies in response to the presence of foreign substances (called antigens) in the body. But there are several kinds of T-cells (T helper and T suppressor cells, cytotoxic killer cells, and so on) to fight off intruders.
T and B-cells (which are lymphocytes) have very different methods of attacking infectious agents, but both of them get a bit of help from a type of monocyte (the other kind of WBC) called a macrophage.
Let’s understand how T-cells work first.
So, the strategy T-cells implement is called cell-mediated immunity. Basically, when an infectious agent invades the body, it is recognised by a macrophage, which in turn signals a T-helper cell (one type of T-cells). An alarm goes off as this happens, and T helper cells begin to rapidly multiply in response to the invasion.
This sudden proliferation activates another type of T-cells called cytotoxic killer cells, which, as their name suggests, are toxic killers. They attack and destroy the infectious agent.
Cytotoxic killer cells are basically assassins, while T helper cells are their handlers.
It is important to note that it is this T-cell component of the immune system that is knocked out by the AIDS virus, leaving you completely defenceless.
By contrast, B-cells’ attacking strategy is called antibody-mediated immunity. Once the macrophage–T-helper cell collaboration has occurred, the T helper cells then stimulate B-cell proliferation. (Basically, instead of multiplying on its own, it delegates the task to B-cells.) This activity generates antibodies, large proteins that will recognise and bind to some specific physical feature of the invading infectious agent.
This specificity is critical. The antibody formed has a fairly unique shape, which will conform perfectly to the shape of the distinctive feature of the antigen — just like two pieces in a jigsaw puzzle. By binding to the specific feature, antibodies immobilise the infectious agent and get it ready for destruction.
Cell-mediated immunity is particularly effective against intracellular pathogens, such as viruses and some bacteria, which can hide inside host cells and evade detection by antibodies. Antibody-mediated immunity is effective against extracellular pathogens, such as bacteria and viruses that are outside of host cells.
This is the gist of it basically, and although it sounds simple, it’s anything but. Let me explain.
Hypothetically, if different parts of the liver have to coordinate together for some kind of mission, they have the tremendous advantage of sitting adjacent to each other. It’s like sitting in the same office building together while planning a scheme. But… the immune system is distributed throughout the circulation, and that’s a problem.
Now, instead of just nudging your adjacent cell with your (cellular) elbow and asking them to do something, you would instead have to send some kind of signal to another cell in a different building in a different city.
So… in order to sound immune alarms throughout this far-flung system, there are chemical messengers that communicate between different cell types using your blood as their transport system.
For example, when macrophages first recognise an infectious agent, they release a messenger called interleukin-1. This triggers the T-helper cell to release interleukin-2, which stimulates T-cell growth.
There are at least half a dozen additional interleukins with more specialised roles, but we ain’t gonna get into dat.
On the antibody front, T-helper cells secrete something called B-cell growth factor to stimulate B-cells during antibody-mediated immunity. Other classes of messengers, such as interferons, activate broader classes of lymphocytes, but again, we ain’t gonna get into dat.
This process of distinguishing the self from the non-self cells works pretty well in general: red blood cells, part of us. Eyebrows, our side. Virus, no good, attack! Muscle cell, good guy! (Although truly insidious tropical parasites like those that cause bilharzia, particularly in sub-Saharan Africa, have evolved to evade your immune system by pirating the signature of your own cells and impersonating them successfully. It’s like they put on a deodorant that has the smell of your cells, and happily bypass the guards and walk into the party.)
Now, even though the immune system is very efficient, once in a while, things go wrong. One obvious kind of error could be that the immune system misses an infectious invader. This is clearly bad news!
Equally bad is the sort of error in which the immune system decides that something is a dangerous invader when it really isn’t. In one version of this, some perfectly innocuous compound in the world around you triggers an alarm reaction. Maybe it is something that you normally ingest, like peanuts, or something airborne and innocuous, like pollen. But your immune system has mistakenly decided that this is not only foreign but dangerous, and kicks into gear. You generally call this an allergy.
In the second version of the immune system overreacting, a normal part of your own body is mistaken for an infectious agent and is attacked. When the immune system erroneously attacks a normal part of the body, a variety of horrendous autoimmune diseases may result.
For example, in multiple sclerosis (MS), the central nervous system (CNS) is attacked. The immune system attacks and damages the myelin sheath (a protective covering that surrounds and insulates nerve fibers), causing inflammation and disrupting nerve communication between the brain and other parts of the body.
Alright, that’s that. But so far in this overview of the immune system, we’ve been concentrating on something called acquired immunity.
Allow me to elaborate: suppose you’re exposed to some novel, dangerous pathogen, pathogen X, for the first time. Acquired immunity has three features:
First, you acquire the ability to target pathogen X specifically, with antibodies and cell-mediated immunity that specifically recognise that pathogen. In other words, you create a bullet that has pathogen X’s name written on it.
Second, it takes some time to build up that immunity when you are first exposed to pathogen X — this involves finding which antibody has the best fit and generating a gazillion copies of it.
Finally, while you will now be geared up to specifically go after pathogen X for a long time to come once that specific defence is on line, repeated exposure to pathogen X will boost those targeted defences even more.
Acquired immunity is an intelligent, learning system, and a pretty fancy and relatively new invention, found only in vertebrates (basically animals that have spine). But it’s a bit slow and expensive to use on every new pathogen that enters your body every second of ever day for as long as you are living.
Therefore, we also contain a simpler, more ancient version of the immune system, one shared with species as distant as insects, called innate immunity.
In its realm, you don’t bother with acquiring the means to target pathogen X specifically with antibodies that will be different from those that would target, say, pathogen Y. Instead, the second any sort of pathogen hits your system, this nonspecific immune response swings into action.
Innate immune response is the first line of defence where the pathogen gets its first foothold (like a cut in your skin).
For example, whenever a pathogen enters any moist mucosal tissue in your mouth or nose, as a first step, the antibodies contained in your saliva launches an attack on the antigens. But instead of targeting and sniping specific invaders individually, these antibodies bomb the site — not the most efficient, but faster indeed.
These antibodies coat the mucosal surfaces like an antiseptic paint. In addition, at the site of infection, blood vessels dilate and become more permeable. This allows fluid containing cells of the innate immune response to slip out of the circulation to infiltrate and attack the immediate area of infection. These cells include macrophages (which you already know of), neutrophils, and natural killer cells, which are some other types of WBCs that mostly take part in the innate immune response.
While the cells fight the microbe, the fluid also makes the area swell up, causing oedema, characterised by an excess of watery fluid collecting in cavities or tissues of the body. This is your innate immune system leaping into action and causing inflammation, but for a good cause.
But like I said, the innate immune response is fast, but not the most effective. There are pathogens that can evade or overcome the innate immune response, which is where the acquired immune system kicks into gear and provides a more specific and targeted response against specific pathogens.
I could get into more details, but in my opinion this would be enough to give you a very very very broad overview of immune function.
I think understanding the mechanisms that are keeping you alive is not just a nice exercise in intellectual curiosity, it is desperately needed knowledge.
If you know how the immune system works, you can understand and appreciate vaccines and how they can save your life or the lives of your loved ones, and approach disease and sickness with a very different mindset and far less fear.
You become less susceptible to snake oil salesmen who offer wonder drugs that are entirely devoid of logic. You get a better grasp on the kinds of medication that might actually help you when you are sick. You get to know what you can do to boost your immune system.
You can protect your children from dangerous microbes while also not being too stressed-out if they get dirty playing outside. And in the very unlikely case of, say, a global pandemic, knowing what a virus does to you and how your body fights it, might help you understand what the public health experts say.
Today I Learned
Nursing isn’t just an effective contraceptive, on the contrary, nursing is the best contraceptive and it probably prevents more pregnancies than any other type of contraception. All you have to do is do it right.
Breast feeding causes prolactin secretion. If you don’t want to ovulate, this is the hormone to have lots of in your bloodstream.
If there is nipple stimulation for any reason (in males as well as females), the hypothalamus signals the pituitary to secrete prolactin.
This is how most women on earth nurse: during the six months or so that she breast-feeds, the average mother allows perhaps half a dozen periods of nursing a day, each for 10 to 30 minutes. Each time she nurses, prolactin levels go up in the bloodstream within seconds, and at the end of the feeding, prolactin settles back to pre-nursing levels fairly quickly. After six months, most modern mothers switch to a supplement, commonly known as a formula, and prolactin levels remain permanently low.
But something interesting emerged from studies of hunter-gatherer Bushmen in the Kalahari Desert of southern Africa (the folks depicted in the movie The Gods Must Be Crazy).
Bushman males and females have plenty of intercourse, and no one uses contraceptives, but the women have a child only about every four years. Initially, this seemed easy to explain: malnutrition induces cessation of ovulation.
However, when anthropologists looked more closely, they found that the Bushmen were anything but suffering.
The Bushmen hunt and gather only a few hours a day, and spend much of the rest of their time sitting around chewing the fat. Out goes the idea that the four-year birth interval is due to malnutrition.
(If you want to abandon society, for whatever reason, and go back to living like in the old days, my suggestion is to choose to be a hunter-gatherer over being a nomadic pastoralist or an agriculturist. Scientists have called them the original affluent society.)
Instead, the four-year birth interval is due to their nursing pattern. See, when a hunter-gatherer woman gives birth, she begins to breast-feed her child for a minute or two approximately every fifteen minutes. Around the clock. For the next three years.
The young child is carried in a sling on the mother’s hip so it can nurse easily and frequently. At night, the child sleeps near its mother and will nurse every so often without even waking her. Once the kid can walk, it’ll come running in from play every hour or so to nurse for a minute.
When you breast-feed in this way, the endocrine story is very different. At the first nursing period, prolactin levels rise. And with the frequency and timing of the thousands of subsequent nursings, prolactin stays high for years. Oestrogen and progesterone levels are suppressed, and you don’t ovulate.
This pattern has a fascinating implication. Consider the life history of a hunter-gatherer woman. She reaches puberty at about age thirteen or fourteen (a bit later than in our society). Soon she is pregnant. She nurses for three years, weans her child, has a few menstrual cycles, becomes pregnant again, and repeats the pattern until she reaches menopause.
Think about it: over the course of her life span, she has perhaps two dozen periods. Contrast that with modern women, who typically experience hundreds of periods over their lifetime. Huge difference!
The hunter-gatherer pattern, the one that has occurred throughout most of human history, is also what you see in nonhuman primates.
Perhaps some of the gynaecological diseases that plague modern women have something to do with this activation of a major piece of physiological machinery hundreds of times when it may have evolved to be used only twenty times.
Timeless Insight
When it comes to reading, you don’t need to finish what you start.
Our desire to finish what we start often works against us. Good books finish themselves. You can’t put them down. Trying to finish a bad book, on the other hand, is like walking through the mud. It’s a drag.
Once you realise that you can quit bad books without guilt, everything changes.
Think of it this way: All the time you spend reading a bad book comes at the expense of a good book. And yes, there are just so so many bad books out there. Don’t waste time on them.
Skim a lot of books. Read a few. Re-read the best ones.
What I’m Reading
I don’t like many (in fact any) self-help gurus or leadership coaches or motivational speakers, mostly because all of them are charlatans, except a very very tiny minority of exceptions. Simon Sinek is one of them.
I may not be huuuge fan of his books (although I can’t say I don’t like them) mostly because they are light reads (I like books that are slightly heavy, where I have to process a bit more, think one or two levels deeper to understand its essence) but his heart seems to be at the right place, and this is very very important.
Infinite-minded leaders understand that “best” is not a permanent state. Instead, they strive to be “better.” “Better” suggests a journey of constant improvement and makes us feel like we are being invited to contribute our talents and energies to make progress in that journey.
— Simon Sinek, The Infinite Game
Tiny Thought
Human culture is capable of defining “groups” very broadly though a complex system of mythology, creating deep loyalty to “imaginary” groups like sports teams, corporations, nations, or religions.
Before You Go…
Thanks so much for reading! Send me ideas, questions, reading recs. You can write to abhishek@coffeeandjunk.com, reply to this email, or use the comments. And… if you feel like I’ve done a great job writing this piece, be generous and buy me a few cups. ☕️
Until next Sunday,
Abhishek 👋
PS: All typos are intentional and I take no responsibility whatsoever!