Your body is a fortress, crafted  through millions of years of evolution.   And I don’t mean just your fists or your teeth.

The little things like your skin,   tear ducts and even the hairs in your  nostrils are all designed to defend you. That’s because they’re protecting  you from even tinier things: pathogens, the microscopic  organisms that make us sick.

You might have heard of them in  vague terms like “bugs” or “germs,” but the small world of pathogens  is actually incredibly diverse, sometimes weird, and often, pretty dangerous. And in this episode, we’re going to  get to know that world really well, from the little creatures that live there to how   our bodies protect us from the  ones that could make us sick. I’m Pardis Sabeti, and this is  Crash Course Outbreak Science! [Theme Music].

In our last episode, we saw how looking   at infectious diseases from  a microbiology perspective can help us understand and  tackle outbreaks better. To a microbiologist, the roots  of disease are infectious agents, the microbes and large molecules that are  transmitted between larger organisms, like humans. To be more specific, it all starts with pathogens, which is what we call the specific  infectious agents that can make us sick.

Pathogens tend to be microbes like  bacteria, viruses, protozoa and fungi. There’s a huge variety of pathogens out there– we’d need a whole other  series to describe them all! but in general, they have a few key features  that help biologists tell them apart. Let’s find out who’s who.

First up are viruses, which are made  up of fragments of genetic material, wrapped in a kind of “coat” made of proteins. Unlike most other pathogens,  they don’t have cells. And depending on who you talk to, they  may not even qualify as living things!

That’s because they need to infect a  cell and use its resources to reproduce. I’m team living thing myself. They do this by latching onto a host cell, injecting their own genetic material into it and  taking over the cell’s functions to multiply.

If they attack enough cells, viruses disrupt the  workings of our organs, causing us to get sick. Smallpox, the common cold, flu, Ebola, Polio,  and COVID-19 are all caused by viruses. Wow, that’s a lot of diseases!

That’s part of why we often focus  on viruses in outbreak science. Our next microbe, bacteria, do have cells. They’re single-celled organisms.

But while other kinds of cells keep  their genetic material inside a nucleus, a bacteria’s genetic material is wrapped up in  circular loops that float freely inside them. Not all bacteria are bad. There’s friendly bacteria like the ones  in our stomachs that help us digest food, and the ones we use to create  fermented foods like kimchi and yogurt.

But the pathogenic kind are much nastier. Once inside the body, they can kill  your cells through direct attacks   or by creating toxins that paralyze them. Other kinds of bacteria multiply so  rapidly they damage entire organs!

That’s what the bacteria that cause  diseases like cholera and tuberculosis do. Protozoa, the next microbes on our  list, are a little more like us. They’re single-celled organisms,  yes, but they are eukaryotes, which means they have a nucleus like our  cells do, and they’re undoubtedly alive.

When they get into our bodies, they can  harm us in ways similar to how bacteria can. One of the most widespread  infectious diseases, malaria,   is caused by protozoa carried by mosquitoes. Then, there are fungi.

These are your molds, yeasts, and  mushrooms, and they’re also eukaryotes. Some are made up of single  cells, some are multicellular, some are harmless pizza  toppings, and some make us sick. Fungi release tiny cells that can  reproduce on their own, called spores.

Certain kinds of pathogenic  spores travel easily in the air, where they can stick to our skin or be inhaled. During an infection, fungal cells multiply, growing into places they shouldn’t  and feasting on the cells they infect! Fungi are responsible for certain skin  diseases such as athlete’s foot and ringworm, and other unpleasant things like oral thrush.

Finally, there are a few pathogen  oddballs, like parasitic worms. Unlike the others, they’re animals…. Animals that live inside people  by feeding off what they eat.

They can even grow large enough  to be seen by the naked eye. I won’t mince words here, it’s… pretty gross. So let’s move on to the equally  weird and fascinating prions.

Prions are just proteins that have  ended up folded into the wrong shape. It doesn’t sound like a bent-out-of-shape  protein would do much harm, but they can be seriously dangerous! If they come into contact with other,  correctly-folded proteins inside the body, those proteins become misshapen too.

Those newly misshapen proteins bend  other proteins out of shape and so on, damaging the organ they’re a part of. That’s why we consider prion  diseases “infectious diseases.” Prions can be inherited or  consumed in certain kinds of food. One example is Creutzfeldt-Jakob Disease, or  mad cow disease, which occurs in the brain.

Okay, that sounds… terrifying. But luckily, prions are super rare! Microbiology is a pretty large field  and we’ve skimmed a lot of the details.

But it should give you an idea of the many  kinds of pathogens that might enter the body. The question is… how do they do it? On close inspection the  human body has lots of holes.

As I mentioned in our last episode,   science demands clarity, so there’s  no shying away from the details here. Some of the holes in the body are  obvious, like your mouth and nostrils. Others aren’t as apparent, like your  tear ducts, ears, anus or genitals.

And although your skin is quite  a good barrier against pathogens, tiny scratches, wounds or  bites can create holes too. All of these holes are the routes  pathogens can take to get inside you. For example, pathogens can be  transmitted by direct contact   with an infected person’s skin or bodily fluids, which is often the case for  sexually transmitted infections.

They can also be picked up from the  surfaces we touch with our hands, and enter our bodies when we later  touch our eyes, mouth or nose. Or an infected person might release droplets  containing pathogens when they talk, cough or sneeze which then  get inhaled by someone else. It could even be more straightforward!

Some pathogens find their  way into our food and water, which we then unknowingly  put straight into our mouths. Others, like malaria, are carried  by animals known as vectors. Vectors are typically bloodsucking  arthropods, like mosquitoes, ticks, and fleas, and when one bites us to feed, they’re  basically creating another hole through which they transmit pathogens  directly into our bloodstream.

It seems like the drawbridge is wide open for  invaders, as far as the human body is concerned, hardly the most well protected fortress! But your body has a whole host of  features to defend you from pathogens. Together, these features form the immune system.

It all starts with physical barriers,   which prevent pathogens from  entering in the first place. Skin physically stops pathogens  from getting into our bodies. What’s more, it’s slightly acidic, which  prevents bacteria from growing on it, and our sweat contains enzymes that  break down bacterial cell walls.

Our eyes are similar. Our eyelashes and eyelids physically prevent  airborne pathogens from reaching our eyes, while our tears contain antimicrobial compounds  that kill anything our eyelashes miss. Other potential entry holes into  the body, like our nostrils, lips,   ears, genitals and anus are lined with mucus, which physically traps pathogens, stopping  them from getting any further into you.

And though it might spread  disease if we’re already sick, coughing and sneezing can eject unwanted  material from our airways that contain pathogens. Finally, we can eject microbes out the other end. Every time we use the bathroom,   we’re also flushing out lots of  unwanted microbes from our systems.

These physical barriers are like the  walls, turrets and moats of the fortress, providing a first line of defense. But should any stubborn pathogens manage to break  through, the second line of defense kicks in: the innate immune system. This system has dedicated cells that attack any  trespassers, so we'll call it a nonspecific barrier.

Monocytes cruise along your bloodstream  looking for anything suspicious, while macrophages and dendritic  cells keep an eye on your tissues. If they find something, they  can digest the intruder. And macrophages will eat anything dangerous  looking, even tattoo ink in your skin!

When a macrophage begins its fight, it calls for help by releasing proteins  called cytokines as a distress signal. At that point, tougher cells like  neutrophils and natural killer cells — yes, that’s their real name — will swoop in to help destroy tougher threats. So the cells of the innate immune system  are like the guards of the fortress, well trained to neutralize most enemies that make  it beyond the physical barriers of your body.

But occasionally, the body needs a more  specific approach in tackling a pathogen, and calls for special forces. That’s where the adaptive immune system comes in. Unlike the innate immune system, the  adaptive immune system is highly specific.

Its cells target distinct  pathogens and continually, well,   adapt to be stronger the next time. Two important members of this specialized  team are the B-cells and T-cells. B-cells are a type of white blood  cell that creates antibodies, which are special, custom-made proteins  designed to stick onto one specific pathogen.

If an antibody binds the  pathogen it’s looking for, the body triggers an immediate immune  response to rapidly destroy the threat. That can look like blocking pathogens  from getting into our healthy cells, or making pathogens clump together, stopping them from infecting more cells and  making them easier for other immune cells to eat. T-cells also look for specific pathogens,  but do it a little differently.

While B-cells and their antibodies  seek out pathogens directly,. T-cells recognize our own infected cells. When they find one, they call in reinforcements:.

Cytotoxic T-cells and Helper T-cells. Cytotoxic T-cells are in charge  of destroying the infected cells, while Helper T-cells coordinate  the rest of the response. They help B-cells produce antibodies by nudging  them into action or releasing cytokines, the protein distress signals  we talked about earlier.

Our adaptive immune system has a secret weapon   that gives us an advantage against  repeated infections from the same pathogen. It remembers pathogens it’s seen before so it  can recognize them more quickly the next time. When T-cells or B-cells are exposed  to pieces of a digested pathogen   they can specialize into memory cells.

This process is called immunological memory. Memory T-cells are like historians, documenting the invader’s attack and storing  that data in our bodies’ long term memory. Memory B-cells, meanwhile, hang out in  the body after the first immune response, ready to spot the pathogen and make  antibodies quickly if it shows up again.

The adaptive immune system is like an elite  guard of soldiers and military intelligence that strategizes to defeat the  more serious threats to your body. And it’s this system that we take  advantage of when we make vaccines. They help our T and B cells recognize a particular  pathogen and prep to defend our bodies against it, without making us seriously sick.

We’ll be talking about vaccines  in more detail in future episodes! Unfortunately, even with all of these  remarkable layers of protection, sometimes things can still go wrong. Pathogens are often sneaky, and have multiple  ways of evading even our strongest defenses.

Sometimes we do get sick, or even get  sick multiple times from the same virus. Our immunity also varies from person to person, so what makes one person  too sick to get out of bed   might look like it doesn’t  affect the next person at all! Our immune system can even overreact to  something that isn’t actually a threat, like a particle of pollen.

In that case, the body will  start up the immune response, releasing the same cytokine  distress signals it normally would, which can cause inflammation and swelling. You might already know this  process by another name: allergies! In the case of hay fever, it may just be annoying.

But a serious food allergy, for  example, could cause anaphylaxis, when the throat swells up so  much that you can suffocate. Similarly, an autoimmune  disorder, like Multiple Sclerosis, is when a body is essentially allergic to   itself and the immune system  attacks our own healthy cells. On the whole though, the immune system does   a remarkable job fending off the  many kinds of pathogens it faces.

Understanding these threats and  supporting the immune system is   a crucial part of tackling  diseases during an outbreak. Individual bodies are just  one part of the picture. In our next episode, we’ll be zooming out  to look at how when groups of people change, the way diseases affect them changes too.

We at Crash Course and our partners Operation Outbreak and the Sabeti Lab at the Broad Institute at MIT and Harvard want to acknowledge the Indigenous people native to the land we live and work on, and their traditional and ongoing relationship with this land. We encourage you to learn about the history of the place you call home through resources like native-land.ca and by engaging with your local Indigenous and Aboriginal nations through the websites and resources they provide. Thanks for watching this episode  of Crash Course Outbreak Science, which was produced by Complexly in  partnership with Operation Outbreak and the Sabeti Lab at the Broad  Institute of MIT and Harvard— with generous support from the  Gordon and Betty Moore Foundation.

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