Immune, by Philipp Detmer taught me a LOT. I came in knowing next-to-nothing about the immune system, and the book does an excellent job of making the individual components both memorable and approachable.

Detmer is a professional Youtube educator, so he does a great job of using vivid imagery and coming back to particular ideas on a regular basis (e.g. Macrophages are the 'black rhinos' of your cells).

I'd highly recommend this for anyone looking to learn more, even if you don't have a strong foundation in biology.

Cells are sand

Imagine your body's cells as being a room filled with grains of sand. The sand itself are the water molecules in your body. Strewn between it are many watermelon sized other molecules which perform particular functions.

Most bio textbooks tend to position cells as either 'chock full of things' or 'mostly empty space'. I found this metaphor to be a good way to reason about the two.

Your skin is a hostile desert

Your skin does an incredible job keeping out bad bacteria, who are all too happy to come into your body. The skin does this by constantly shedding itself, and remaining a high-acid environment, that is inhospitable for bacteria to live upon. You can think of it like a desert, hundreds of miles wide, that doesn't allow bacteria to spawn there.

The mucus membrane

We often think of our skin as the big surface area for attackers, but that isn't really true (see the hostile desert piece above)! In reality, the biggest surface area is our mucus membrane: primarily our lungs and digestive system. These areas tend to have higher moisture content and be a key area where viruses and bacteria enter our systems.

The innate immune system

Your immune system is split into two parts: the innate immune system, and the adaptive immune system. The innate immune system is basically a catch-all to destroy any foreign matter, and doesn't really have any specialized function. The adaptive immune system changes itself to adapt to each new intruder.

The innate immune system consists of several components...

  • Macrophages are sort of like the general purpose defense mechanism for your immune system. They basically surround and ‘eat’ other cells, referred to as the "black rhinos" of the immune system
  • Neutrophils are the ‘rampaging warriors'. They will rush to a site needing immune defense and then release a bunch of acid and internal DNA nets which will destroy foreign (and sometimes friendly) cells. Fun fact, when your snot turns green, that's the internals of Neutrophils!
  • Dendritic cells carry information back to the central nervous system via the Lymph node network. They are the ‘dionesyian’ cells, sucking up as much raw information about what is going on at the site of infection, and then bringing it back to the central lymph nodes for the trained immune system.’ cells, sucking up as much raw information about what is going on at the site of infection, and then bringing it back to the central lymph nodes for t-cells to train on.
  • The complement system is a strange part of the immune system that I’d frankly never heard of! It’s a set of individual proteins that self-assemble around foreign bacteria cells. Think of it as a bunch of flies that cover cells, and then can activate into killer bees.

These individual cells contain thousands of receptors that help them identify the various attackers and inputs. A good example is ‘flagella’, outside bacteria have these simple structures which allow them to move quickly, but cells don’t really have them. If a cell detects flagella, it will immediately start attacking.

In some cases, they respond to cytokines, which effectively are signaling devices for how cells should move. You can think of a cytokine as some sort of protein which gets released that interacts with other receptors on cells. It's sort of a

The adaptive immune system

The adaptive immune system is much more complex. Cells here train to identify very specific receptors that intruders might have. In this way, humans are able to adapt to novel viruses, without getting totally wiped out.

  • t-cells. these cells are born in the 'thymus', and each one has receptors to match a handful of different varieties of intruder and bacteria. You can think of them as specialized assassins, seeking out individual intruders (or our own cancerous cells) and destroying them.
  • the thymus is the intensive training academy for t-cells. if a t-cell cannot distinguish self vs other, it will immediately be killed. the t-cells are too effective at killing cells to be left alone if they identify your own cells as targets, which leads to auto-immune diseases.
  • b-cells are helper cells which cover other cells in antibodies. these antibodies are small proteins which have a bunch of different properties, some of which is to signal to t-cells that they should destroy the cell, other times they may just disrupt a cell. b-cells can be 'long-lived' memory cells and circulate for decades, which is where our immune memory is built.

Viruses vs bacteria

Viruses are crazy because they effectively took the "simplest approach to life". Instead of being a bunch of fully-formed cells that re-create themselves, it's just little bits of DNA that make their way into your own cells and then start re-producing there.

The fact that viruses are little bits of DNA make them complicated for two reasons. 1) they are very small vs a cell which would display certain antigens and 2) they incorporate themselves into the DNA of your cells and then use natural replication processes to spread from cell to cell.

Apparently our genome is 8% viral!

MHC-1: the display windows

So, how does your immune system detect a virus, something that is so small that it can't easily be identified, but that also infects your own cells?

Enter MHC-class 1 molecules. These are the 'display windows' to your cells that showcase what is going on inside of them. If a cell doesn't have enough of these, or shows some sort of fishy piece of DNA, a t-cell will come along and destroy it.

How vaccines work

We've made weaker and weaker versions of natural virus (in the same way that we've domesticated dogs from wolves). Notably mRNA vaccines don't work this way, those happen by delivering small bits of mRNA for our body to process that don't have any of the nasty side effects that viruses might have.

Auto-immune disorders

A big part of the immune system is determining the difference between 'self' and 'other'. There are dozens of 'checks and balances' when it comes to growing new t-cells and b-cells–if any of them are 'over-eager', they will be killed.

In this way, your immune system is mostly trying to keep itself balanced. If it's too active, it will spend time killing your own cells and cause auto-immune issues. If it's not active enough, it will let viruses into your system.

HIV is an interesting virus in that it both replicates and mutates very rapidly. Many of the mutations won't be viable for life. But enough of them are viable and will cause your immune system to have a very hard time trying to pin them down and attack them.