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H+ Foundations: High-Level Immunology

Transhumanism, it’s time we had a talk. I know you’re excited, giddy, even, about the prospects of medical immortality, mechatronic implants, stem cells, lollipops and genetic engineering helping you achieve the beingness you so badly want to become. And I’m glad you’re excited, I am too. But we’re getting ahead of ourselves over here and our excitement is somewhat decoupled from the amazing complex processes underlying all these disruptive technologies. In particular, I see a lot of talk about longevity and implants completely devoid from any talk of the molecular mechanisms at work beneath their (hypothetical) successful implementation.

And while we don’t implicitly need such fine-grained understanding to discuss the implications of such technology, I maintain that that very understanding can accelerate our discourse and progress substantially. As such, I intend to begin by  describing these mechanisms and how they work, from the top down cell population interactions to the stupid awesome mathy dynamics of molecular signaling that drive them. We’re going to begin with a descent jaunt into immunology so that, in the coming months, we can get dirty with inflammation and implant rejection.

H&E images of polyimide devices were taken to characterize the cell behavior in the central nervous tissue immediately surrounding the electrode device. Devices were implanted in various areas of the brain tissue. Sections were processed and stained at various depth from the implant surface to determine the cell behavior alongside the implant. The scale-bar in each image represents 100 ¹ m. a)-c) Three uncoated polyimide devices were implanted to determine typical cell density along the device. d)-f) Three PGA coated polyimide devices were implanted to determine typical cell behavior around the device. Arrows show the increased cell density around the PGA coated polyimide electrodes.  From Journal of Undergraduate Research 1, 36 2007, Biocompatibility of polyimide-based neural interfaces for chronic implant applications.

Inflammatory processes are vital to wound healing and pathogen clearance in an infection, but are also implicated in aging and conditions related to aging. Implant rejection is, in itself, also an inflammatory process. Inflammation is something that can descend at any site within the body because the system that causes it circulates throughout the body in the form of various lymphocyte flavors, otherwise known as white blood cells. That system is the immune system, of which the are two. Technically speaking, inflammation is a bib term for any sort of immune reaction but colloquially speaking it refers to those immune reactions that have gotten out of hand, whether they’re causing asthma, ulcers, or your magnetic implants to ooze pus.

Now the first immune system is the innate, and the second is the adaptive. They talk to one another a lot and their chatter is generally very important but occasionally noisy (as in allergies). Their entire purpose in life is to distinguish harmful stuff that isn’t part of you from nonharmful stuff that is part of you, as well as that which was part of you but is now behaving badly and become harmful. They are also supposed to ignore stuff that isn’t you and also harmless, like pollen. But that doesn’t work so well sometimes. There are intricate levels of control wrapped around each of these processes and multiple inflammatory diseases arise from dysregulation thereof. We’ll be getting into those a lot more.

Within the innate immune system, you mostly have phagocytes such as macrophages, neutrophils, and mast cells. They carry around evolutionarily conserved pathogen sensors that have very strong affinities for bits of pathogens that tend to pop up a lot, such as the lipopolysaccharide shell of Gram-negative bacteria. They tend to react extremely fast and a lot of them live scattered about within your skin or ride around your bloodstream continuously to reply to breaches in your hull quickly. They’re born in your femur bone marrow and mature in your bloodstream. They’re mostly good guys, and they tend to respond to pathogenic threats by swarming and enblobbinating (not a technical term) the pathogens, then digesting them to internal goo.

The adaptive immune system is a bit more complex. The adaptive immune system is all about T- and B-cells, which live in your lymph nodes and spleen. They, too, are born in your bone marrow, but they migrate to and mature within the aforementioned organs. However, most of them die because editing. You see, when a T- or B-cell is born, its T- or B-cell receptors are randomly slapped together from the many varying copies of their encoding genes that each individual carries. And after that random swap, they undergo further mutation by adding a few base pairs here and there to make things truly novel. As a result, each T- or B-cell receptor is unique and will only bind to a very specific antigen. If it doesn’t see that antigen in its short lifetime, it dies because why should the body bother keeping a useless cell around? Accordingly, there’s a massive background churn of new T- and B-cells being made all the time just in case 1 specific antigen needs to be bound at any given time. However, the body does have a basal rate of this churn and increases it when pro-inflammatory markers are elevated following a pathogen incursion.

So where do antigens come from? Well, they come from the pathogens. When a specific phagocytic innate immune cell digests a pathogen, it dices it up into T-cell-sized chunks and here comes the ‘choo-choo’ spoon as that innate immune cell travels to the lymph nodes or spleen to see if any of the T-cells there will eat its digested pathogen bits. If one does eat it, and binds to it with strong enough affinity to trigger intracellular effectors, it is on and that one T-cell begins to bloom and divide and mount an adaptive immune response against that 1 special antigen. So as the T-cells bloom they talk to B-cells which then make antibodies that, conveniently, are very very good at binding that one antigen, which is found on the pathogens in question. So as B-cells pump those antibodies out into the bloodstream, pathogens become coated in them. And that coating is like lighting up a homing beacon for phagocytic cells directly on the pathogen’s ass. Meanwhile, specialized types of T-cells also join the battle and provide chemical logistical support for the entire effort. In effect, this makes the job of the innate immune gobblers much more specific and deadly and enables them to rid your temple of its invaders.

The link between innate and adaptive immune systems comes down to that particular special type of phagocyte mentioned above: the dendritic cell. This happy chap straddles the interface between innate and adaptive immune systems by participating in the initial innate immune response and then communicating with the adaptive immune system to elevate the response before it can get out of hand.

This communication is super-important to inflammatory processes and is something we will keep coming back to as we delve further into these topics and how they relate to transhumanist technologies more specifically in the coming weeks. Until then, stay awesome.