How HIV infects us: Mucous membranes, dendritic cells, and lymph nodes

- [Voiceover] How does HIV actually infect our cells? What exactly happens when you get an HIV infection? Well, to find out, let's follow a little HIV particle, an actual virus, through what it does and where it goes in order to infect a human. So let's start by drawing some skin here. Actually, let's say this is mucus membrane. So the soft, most areas not quite protected like everywhere else on your body that's covered by normal skin. So you'd find these mucus membranes inside your mouth or in your throat or your noes our inside the vagina or at the tip of the penis or in the rectum, or anywhere in your digestive tract, really, any and all of these are mucus membranes and remember, this is relevant, because the most common way HIV is spread is by sexual contact, which is when these areas or some of these areas are likely to come into contact with infected sexual fluids from each other. And, just to jog your memory, remember the second most common way HIV is spread is when it's directly put into your blood from an unsafe needle or from blood to blood contact with an HIV infected person. And, you know, we can sort of intuitively see how HIV can attack our white blood cells like our CD4 T helper cells or our macrophages when it's directly put in the blood stream. That bit's a little obvious. But what's less obvious is how HIV gets into our bodies across our mucous membranes, right? I mean, they look like barriers to me. Well, it turns out that we have these really interesting little immune system cells imbedded within and throughout our mucous membranes. And these are called our dendritic cells. And these cells are really quite key in HIV infection. What they do is they protrude their little limbs, essentially up to the surface of our mucus membranes because their job is to sort of sample the environment to look for bacteria or viruses or any other threats to our health. And practically speaking, what they do is they sort of continually grab on to particles that they find sitting on top of our membranes here and they pull them in across the membrane to check them out to see whether they found a good reason to activate our immune system or not, alright? They actually have the ability to kick off a pretty big immune reaction depending on what kind of particle they've found. So what they do in a normal scenario is that if they find something they're worried about, maybe a virus or a bacteria or something like that, they internalize it and then they kind of cut it up into a few pieces and then they display little pieces of it which, at this point, are called antigens on their surface, because essentially they wanna get other immune cells attention. They're essentially saying, "Hey, guys, look what I found! "Let's make some immune cells that our targeted to these "little pieces here, let's wipe this thing out." And really, really, really importantly, while they're doing all of this, all of this break down and displaying of foreign invader antigens, they're also on the move. They've sort of picked up shop and they're already on their way through the blood stream, or through the lymphatic system on their way to one of our many lymph nodes. They usually go to the closest one. Lymph nodes, by the way, are a really important part of our immune system where a lot of our immune cells, particularly our lymphocytes, hang out and sort of filter through our body fluid for any pathogens that they might need to become sensitized to and respond to. You can think of these lymph nodes as police stations where a lot of our cops hang out waiting to be briefed on their next task, to be shown wanted posters, so to speak. This is standard practice for our dendritic cells, by the way. The normal sort of every day life for these guys goes something like they hang out in the mucousal surface, they find pathogens, they carry them to the lymph nodes to alert the lymphocytes. This is just a normal day for them at this point. The problem with HIV though is that it's not quite like the other pathogens, either bacteria or viruses. I mean, some of it gets degraded, right? Chopped up and displayed to the lymphocytes and the lymph nodes here, sure. But some of the HIV actually gets transmitted to the lymph node in tact which is no good. And I'll tell you how that happens. There's three sort of main ways that our dendritic cells sort of misguidedly bring intact HIV to our lymph nodes. One way is by what's called an infectious synapse where there dendritic cell essentially grabs on to HIV particles using its plasma membrane and then a protein on its plasma membrane and it essentially carries it, just like this, to the lymph node and then it sort of hands it off, hands off the little HIV particle to a T-cell to deal with, which usually results in that T-cell becoming infected. Another way is where the dendritic cell endocytosis a group of HIV particles, bring that endocytosed group to the lymph node and then exocytoses them right inside the lymph node where all you other immune cells get exposed to them and can thus get infected as well, right? Not very thoughtful of the dendritic cell to do that. And the third way is that HIV will directly infect our dendritic cell at some point during initial contact either at the mucus membrane or during the period of time when the dendritic cell is traveling to the lymph node. And throwing an infected dendritic cell into a lymph node is generally a terrible idea, probably the worst idea anyone could ever have, because after becoming infected, the dendritic cell will start pumping out copy after copy after copy of HIV particles that are just as infectious as the first one. But, you might be wondering, well, how does infection of an immune cell by HIV result in more copies of HIV being made? And that's a great question and that's actually the standard way that viruses work. They sort of highjack our cellular machinery and they use it to create lots and lots of copies of themselves that can then sort of leave the infected cell and go on to infect more of our other cells to sort of repeat the whole process. HIV though, it sets itself apart from almost every other virus because the way it does this highjacking is a little more different and a lot more sneaky than other viruses. And I'll cover how it highjacks when we look at how HIV particles infect their preferred targets, our T-helper cells.