Immune: A Journey Into the Mysterious System That Keeps You Alive

by Philipp Dettmer

You got to know your soldier cells, your intelligence networks, special organs, protein armies, specialized superweapons, and the mechanisms of how they work together! Now that this stuff is covered we have an opportunity to see what happens when all of these great systems fall apart. What happens when a pathogen interferes with your T Cells, what if your immune cells are fighting way too hard and begin hurting you from the inside, what can you do to boost your immune system, and how is it protecting you against cancer?

So while the antivenom will work fine the first time, the second time you might be immune to it because your body might make antibodies against the antibodies from a horse or bunny. This is one of the cases where the immune system just could not have expected that modern medicine would come up with creative solutions like pumping venom into a horse and then using its blood for ourselves. Which is fair so we can’t really be annoyed too much with our immune system in that case.

The main victims of the virus are your Helper T Cells. Yes, all the horror of HIV and AIDS is because it knocks your Helper T Cells out. If you read this far you probably understand how important this cell is and how much of your defense relies on them.

As a species we are incredibly lucky that HIV is not super easy to contract.

Most HIV infections happen through sexual contact, through small unnoticeable injuries,

where the virus passes through the defensive layers of epithelial cells.

HIV is a retrovirus which means that it intrudes and merges with your genetic code, your most intimate expression of your individuality. In a sense HIV becomes a part of you forever. But a corrupt version of you.

Do you remember our virus metaphor with the silent soldiers that kill citizens in their sleep? HIV is like a soldier killing their victim but then flaying their corpse and wearing the skin as a costume to walk around the city during the daytime.

The first stage is the acute phase. It is thought that Dendritic Cells are among the first cells that HIV infects and takes over.

for: The T Cell dating areas in your lymph node megacities. Once the infected Dendritic Cell arrives here, HIV has easy access to countless T Helper Cells. So HIV really acts like a sleeper agent wearing the skin of its victims to invade the headquarters of an enemy country.

During this phase your body reacts to HIV like it does to all viruses, using the regular mechanisms and weapons, activating the adaptive system—and this is when you first might notice the infection.

At some point, enough Killer T Cells and Plasma Cells will be activated and devastate the virus, killing infected cells left and right and eradicating billions of viruses.

Now the chronic phase of the infection begins. Most types of viruses would not survive the onslaught of the immune system—but HIV has many extraordinary methods to survive: First of all, the virus does not spread just by making many copies of itself until the cell bursts—it is much more careful and works to keep its victims alive as long as possible.

Second, it has a few extra-sneaky ways of finding new victims. In Cell-to-Cell Spread, the virus can be transmitted from one cell directly to another one. Here, HIV makes use of an important mechanism of your immune cells: Immunological synapses. When immune cells interact directly to activate each other, they sort of bash their faces together and lick each other’s cheeks. Which means, getting very close and touching each other with many short extensions, called pseudopodia. It looks a bit funny, like many short fingers reaching out of the cells—this is the way many immune cells check each other’s receptors. And these interactions can get hijacked by HIV—it uses this close connection to jump from one cell to another.

And it has a very high success rate to infect another victim compared to the floating-around-randomly strategy that most viruses employ. This way, HIV uses interactions between cells and jumps from infected Helper T Cells to Killer T Cells, from Dendritic Cells to T Cells, from T Cells to Macrophages.

HIV can hide very efficiently this way. Even if the immune system flares up and kills most of the infected cells from time to time, the virus only has to sit idle in a few cells inside a lymph node to be carried around your whole body again, always in close vicinity to all the cells it wants to get close to!

HIV also can lie dormant and do nothing in cells for long periods of time waiting for the right time to become active.

So when an infected Helper T Cell begins to multiply, HIV awakens and makes thousands of new viruses within hours. This is so effective that even if Killer T Cells are around looking for it, the virus is able to produce a lot of new viruses without being caught and to infect a lot of new cells.

What makes HIV so incredibly dangerous is that it operates on a completely different level in terms of genetic variability. The genetic code of HIV is extremely prone to copying errors—on average, every time the virus makes a copy of itself it makes an error. Which means even in a single cell there are numerous different variants of HIV.

1. HIV destroys itself because it mutates in a way that disables itself or it becomes less effective. 2. The mutation does not help or harm and nothing changes. 3. The virus becomes better at avoiding the defenses of the immune system.

Immune System about a week to make thousands of Killer T Cells and millions of antibodies that are extremely good at hunting HIV down—but already there are numerous new viruses that have new and different antigens! Different enough that the Killer Cells and Antibodies you just made may be useless against them.

For them, the virus your Adaptive Immune System adapted to is already old news and irrelevant. HIV is always a step ahead of the immune system. And so in the chronic phase of an HIV infection your body is still teeming with the virus. On average, in this phase, a single milliliter of blood contains between 1,000 and 100,000 virus particles.

By infecting Dendritic Cells, the virus gets a taxi into HIV heaven: The lymph nodes, which are filled top to bottom with Helper T Cells. HIV can build reservoirs in these cells and stay hidden indefinitely. When Helper T Cells begin to proliferate massively, they do so at lymph nodes, which is the ideal place for HIV to also make millions of new

This is still not the worst part. Think about what HIV really does by specifically attacking T Cells: It destroys and kills the cells that the Adaptive Immune System needs to properly activate B Cells and Killer T Cells.

And although your immune system is giving its all, the cards are stacked against you.

As the years pass, the total amount of Helper T Cells is slowly getting lower and lower and lower. Until one day a critical threshold is reached and the Adaptive Immune System collapses.

The last stage begins: profound immunosuppression. AIDS, the Acquired Immune Deficiency Syndrome, begins. What this means is that your Adaptive Immune System is basically out of order, which demonstrates how tremendously important it is. Hundreds of pathogens, microorganisms, and cancers that are usually not the slightest problem for your body now quickly become dangerous and lethal.

Because to fight cancer, you need your Adaptive Immune System, Helper and Killer T Cells in particular, cancer now can thrive with very little opposition. If AIDS breaks out the situation quickly becomes dire and dangerous. The leading causes of death are various forms of cancer and bacterial or viral infections, often a combination of all three. Basically everything your immune system usually protects you against.

HIV infections used to be a death sentence, with the disease marching towards an eventual outbreak of AIDS that was soon followed by death. But thanks to an immense and unparalleled effort of the scientific and medical community, for people receiving proper treatment, HIV has turned into a chronic disease that is manageable.

The answer is a bit depressing: Attention and money. It is easy to forget that HIV used to be a new pandemic once and a very shocking and scary one. In 2019 there were still around thirty-eight million infected people around the world. When HIV and AIDS emerged it caused panic in the establishment, leading to an outpouring of resources and attention that was unprecedented. Humanity really wanted to get results, fast (as a happy

day. Similar things could be observed with the vaccines for COVID-19, which broke even the best speed record. In the end it really seems to be a question of what is a cure worth to us and how desperately do we want it. Another testament to the fact that humans really could solve all of their major problems if they were better at prioritizing.

Your immune system has the power to kill you in about fifteen minutes. People who suffer from allergies have experience with this dark side of their defense network.

Being allergic means that the immune system massively overreacts to something that might not be all that dangerous. It means that it mobilizes forces and prepares to fight, although there is no real threat present.

most commonly immediate hypersensitivity, which means that symptoms are triggered very quickly,

A short piece of protein, say from crabmeat, that can be recognized by your adaptive immune cells and antibodies and that causes allergy is an allergen.

Here the most annoying part of your whole immune system does its thing: The IgE Antibody. You

can thank the IgE Antibody for a lot of your allergy-related suffering. (They actually have an important job they don’t get to do as much nowadays, but more on that in the next chapter.)

IgE is produced by specialized B

your skin, lungs, and intestines: Where they can do the most damage—presumably to enemies that might overcome the walls of your defenses—but in reality mostly to you. What do IgE Antibodies actually do when you suffer from an allergic reaction?

good. The allergen floods your system and for some reason, B Cells that are able to bind to them with their receptors are activated.

Now, after the exposure to the crabmeat, a lot of IgE Antibodies that are able to attach to the crabmeat allergen are in your system. But IgE Antibodies by themselves would not be

problematic as they are not particularly long-lived and dissolve after a few days. They need help to become a problem from a special cell in your skin, lungs, and intestines that is especially receptive to IgE Antibodies: the Mast Cell.

The job of the Mast Cell is still debated by scientists—some think it is crucial to early immune defenses and others give it more of a secondary role. What we know for sure is that Mast Cells serve as inflammation superchargers. And unfortunately, they do their job with a bit too much enthusiasm in the case of allergic reactions.

This causes virtually all of the very unpleasant things that you experience during an allergic reaction: It tells the blood vessels to contract and let fluid stream into the tissue, causing redness, heat and swelling, itching, and a general feeling of unwellness.

Histamine also stimulates the cells that produce and secrete mucus to step up their game, giving you an extra, unnecessary flow of snot and slime in your respiratory system.

histamine can cause the smooth muscles in your lung to contract and make breathing hard or even impossible. It is not so much that you can’t get air

in, it is more that the air inside your lung is trapped and getting it out again becomes really hard.

extra fluid and mucus fill up the lung, while it becomes harder and harder to actually breathe.

Once Mast Cells activate and degranulate, they also release cytokines that call for allergy reinforcements by another special cell:

Basophils serve as a sort of second wave of horribleness. Once Mast Cells have caused the first wave of allergic reactions, they need to replenish their destructive histamine bombs and are temporarily out of order. Basophils fill that gap and make sure that the allergic reaction doesn’t stop too quickly. They are probably really proud of themselves too, thinking that they are doing important work, innocently setting the body on fire while you are scratching your skin or emptying your