The innate immune system

This article will start a series of article on the immune system. This topic is what made me go into science, and get my degree in immunology. First, I found it fascinating how well « thought-out » the immune system is: through centuries of evolution, the immune system adapted to so many different environments that it is able to protect us from virtually anything. It also have many failsafe mechanisms that in theory, it is an invincible system. However, we will see that it is not the case. I also loved the immune system because it is often presented like an epic battle. Learning immunology was more like listening to fairytales that were happening within our own bodies. This specific article will talk about the innate immune system. This is the first line of defense our body has.

Like any epic stories, we first need to introduce the opponents: our body is the good guy, or in scientific terms, the self. The bad guys can be any viruses, bacteria or pathogen that want to infect us. We call them the nonself. The self vs nonself discrimination is at the core of the immune system: any molecule identified as nonself will trigger the immune system. On the contrary, molecules that are from our body will not be attacked. This differentiation is essential for our survival and in later articles we will see that failure to differentiate self and nonself leads to diseases. [source].

When the pathogen decides to attack us, it has to go through our fortress first. It is composed of our skin, our intestines, or any part of our body that can be in contact with outside molecules. However, the pathogen is tricky: it will try to disguise itself to enter the cells. That’s when the cells in our fortress intervene: when the pathogen interacts with the cells, it will bind to proteins called pattern recognition receptors (PRR), and as their name suggest, they try to estimate whether the molecule is self or nonself based on patterns they already know. If the pathogen is recognized as nonself, the alarm is rung. The cells will produce a bunch of proteins to start the immune attack. These proteins are called cytokines, which have various effects depending on the cytokine produced. One of them is to act like messengers. They will tell the body where it is attacked and start a process called inflammation [source / source].

Inflammation is one of the biggest reaction during the immune attack. The release of cytokines will increase the blood flow towards the site of attack. This will help the attacking cells to come for help. Inflammation is always accompanied with these four symptoms: heat, swelling, redness, and pain. Most of these are caused by the influx of blood, except pain, which is due to cytokines activating neurons. While our fortress was holding off the pathogen, more competent cells have arrived at the site of infection. These cells are collectively known as white blood cells, or leukocytes [source / source].

Now the real fight is starting: The fortress was not able to hold off the pathogen, and there is a new problem: most pathogen either hide or reproduce within our own cells, especially viruses. Therefore, cells in our fortress are likely compromised. Infected cells are dangerous: in cases of viruses for example, infected cell will have viral DNA or RNA and express it, which can either cause many other viruses to be produced or kill off leukocytes. Leukocytes now have to fight infected cells and prevent the pathogen to enter the bloodstream. If it does, it will be able to spread in the entire body and cause massive damage. Leukocytes have many ways of preventing this, but I will only mention two. The first one if phagocytosis. Phagocytosis simply means eating cells. Several leukocyte have phagocytotic activities. One of them is the macrophage. It is able to eat pathogens that do not enter cells, like bacteria, and destroy them. It can also eat cellular debris, which contain dangerous pathogenic material. The second one is a way to kill infected cells. Since these cells express proteins from the pathogens, they can be recognized by leukocytes. One such leukocyte is accurately named the natural killer cell, or NK cell. These cells will attach to infected cells and release proteins to perforate the cell. And like a balloon, these cells will lose everything that is inside them and die. The macrophages then pick up the debris to finish up. There are many other ways the leukocytes work but these are the most common ways. [source / source / source].

At this point, this battle can have two outcomes. Either the leukocytes win, and the body is protected. If the pathogen wins, then the body requires more help. For this, a leukocyte named dendritic cell will act as a messenger: they will phagocytose a pathogen and keep a tiny piece of it, called an antigen. It will then exit the infection site and activate the second part of the immune system: the adaptive immunity [source / source].

This is the end of our first « episode » on the immune system. The innate immune system is an essential part of our defense: it is fast, and it is very efficient. It is so efficient that the innate immune system is almost the same in every vertebrate, and even the fly has a very similar innate immune system [source]. Its mechanisms have adapted through the years to offer us a great protection. But there is a flip side to this coin: the pathogens have also adapted to us. Every single event I have mentioned today can be neutralized, blocked, or evaded by some pathogens. Even the self vs nonself discrimination can be tricked. This is also why I love studying the immune system: there is an eternal tug of war between our body and the pathogens, and it will only make us stronger, but being able to study it can make the body even better at protecting itself. Next week, we will continue to follow our dendritic cell and see how it can bring more help.