We're continuing our series on vaccines, with support from the National Institute for Healthcare Management Foundation. Last week we talked about the history of vaccines, and this week, in the third of the 6 episode series, we're talking about the immune system. We'll address the basics of how the immune system works and how different vaccines exploit that system to provide immunity without causing illness, ending with a quick stop at the intersection of vaccine and herd immunity. That's the topic of this week's Healthcare Triage.

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The immune system is incredibly impressive. We should all take a moment to appreciate that our bodies contain mechanisms to identify and destroy any number of foreign pathogens that we encounter in a lifetime, and in most cases are able to carry out this work without causing a substantial or lasting harm.

After that we should take another moment to appreciate the human endeavor behind our understanding of these mechanisms, and the ingenuity behind our ability to exploit them to our advantage – talking about vaccines here – and that we're nowhere near total understanding, we've come a long way and greatly reduced the burden of human disease.

There are entire textbooks covering what we know, but we're gonna do our best to cover the very basics in one episode.

There are two general sides to the immune system coin – the innate immune system and the adaptive immune system. You are born with an innate immune system that is essentially ready-to-roll, and you develop your adaptive immune system over time via exposure to various pathogens.

The innate immune system is rapid and nonspecific, meaning it reacts within minutes to hours to any potentially harmful antigen it detects. Remember that an antigen is a pathogen or piece of a pathogen that is foreign to your body.

The innate immune system includes physical barriers such as your skin, as well as several cellular components including white blood cells called macrophages that essentially swallow and digest things like foreign material and dead or dying cells. They are also able to present antigens to T-lymphocytes. Which we'll discuss in a moment.

And of course there are several other key players in this system including, but not limited to, natural killer cells, neutrophils, pattern recognition receptors, such as toll-like receptors, and dendritic cells. These types of cells carry out immune duties such as detection and elimination of pathogens, presentation of antigens to other immune cells, and amplification of antimicrobial and inflammatory responses. The innate immune system cannot learn about or adapt to pathogens but it's your first line of pathogen defense.

The adaptive immune response is mobilized by the innate immune system when it cannot neutralize an infection on its own. This part of your immune system is slower but much more specific, meaning it builds up specific defenses against individual pathogens, but that building process can take days to weeks after first exposure to a pathogen. This is also referred to as your acquired immune response, because it's the part of your immune system that learns as you go, developing memory for specific pathogens so that it can better fight them in the future. This part of the immune response evolved less that 500 million years ago and is unique to vertebrates.

It has two types of responses: the cell-mediated response which is handled by T-lymphocytes, and the humeral response which is handled by B-lymphocytes and antibodies. The T-lymphocytes are a defensive white blood cell that are capable of many things including directly killing infected cells. B-lymphocytes are also a defensive white blood cell. Their major responsibility involves production of antigen-specific antibodies.

In short, antibodies are proteins that recognize the antigens for which they are made, attaching to, and neutralizing them to prevent them from causing you harm. There are, of course, other cellular components involved in the adaptive immune response, but T and B Cells are the only cells that can specifically recognize and respond to individual antigens.

When an infection is over some of those T-lymphocytes stick around. They remember the pathogen and are able to act quickly if it appears again at which point the B-lymphocytes are able to produce those antigen-specific antibodies to attack the pathogen.

Long story short: You become infected, meaning a pathogen has infected your body and begun to multiply – a full on attack. Your innate immune system raises defenses almost immediately, and if it cannot neutralize the infection on its own, it engages the adaptive immune response. When this happens, T- and B-Cells (along with many other cellular buddies) join the defense. The T- and B-Cells are the MVPs thanks to their particular powers of memory. Once introduced to a pathogen, they learn and remember it, which is why we call it the adaptive immune response.

Should that pathogen dare to show its face again, there are T-Cells that know it well, become activated by its presence and there are B-Cells that are ready to produce antibodies made specifically for that pathogen. Long story shorter: it's amazing.

Even more amazing is that we were exploiting this system to avert disease before we knew about how most of this worked. We covered that history in the first episode of this series. Definitely go back and watch it if you haven't.

Basically vaccines imitate infection in order to develop the host's immunity to a particular disease, but they do it without causing illness. This is accomplished in several ways. All of which we touched on in the second episode of this series but I'll do a quick review right now.

Some vaccines contain a live version of the virus or bacteria, but it's a version that is significantly weaker that the naturally-occuring virus or bacteria. Its presence in the body still grabs the attention of the immune system, but it's not strong enough to cause significant illness. These are called live, attenuated vaccines and include the chickenpox vaccine as well as the measles, mumps and rubella vaccine. This type of vaccine is extremely effective but cannot be giver to certain groups, such as children with weakened immune systems.

Other vaccines contain an inactivated version of the virus or bacteria meaning the virus or bacteria has been killed. We have both live and inactivate versions of the polio vaccine. Inactivated vaccines usually require multiple doses to elicit and maintain immunity.

Subunit vaccines only contain parts of the virus or the bacteria rather the whole thing. The whooping cough vaccine, a component to the DTaP Diphtheria, Tetanus, and Pertussis vaccine, is a good example of that.

Toxoid vaccines prevent disease via use of a weakened form of the toxin produced by a disease-causing germ. Diphtheria and tetanus vaccines are good examples.

And lastly, conjugate vaccines fight off bacteria whose antigens are coated with long chains of sugar molecules called polysaccharides. This coating makes it hard for the immature immune system of children to recognize the antigens, so a conjugate vaccine (as opposed to a pure polysaccharides vaccine) links the polysaccharides to an easily-recognized antigen, allowing immature immune systems to react to the coating and form an immune response. The Haemophilus influenzae type b vaccine is an example of this.

So, different vaccines elicit immune responses in different ways and with varying degrees of success, but all take advantage of our natural immune defenses by imitating infection. This is preferable to a natural infection because severe illness can be avoided. When a contagious disease hits a previously unexposed population it can spread fairly quickly because no one is immune. Eventually, herd immunity would be achieved but at high cost because a certain portion of that population would experience a severe form of the disease up to an including death.

Herd immunity, of course, is when a large portion of the population is immune to a disease, thereby limiting spread and indirectly protecting those who are not immune. Vaccination allows us to achieve herd immunity without risking the lives of a number of people within that population via the disease burden associated with natural infection.

That's a pretty big deal. And one of the many reasons that vaccines are considered to be among the greatest public health achievements of all time. Unfortunately, not everyone agrees. Next week we'll talk about the history of vaccine backlash and misinformation. Promises to be interesting.

[Outro]
Hey, did you enjoy this episode? You should watch all the episodes in this series, starting with episode 1 – there's a playlist you should go check it out. We'd like it if you'd like the video and subscribe to the channel so you never miss anything. Also going on over to https://www.patreon.com/healthcaretriage help support the show even during a global pandemic. I'd like to especially thank our research associates James Glasgow, Joe Sevits, Josh Gister and Michael Chinn, and, of, course, our Surgeon Admiral, Sam.