Transcription
All right, ninja nerds.
So, the goal of this video is to cover an entire adaptive and innate overview. And again, I get a prize if I win if I do this under 20 minutes, so we're definitely trying to make this kind of quick.
Good overview here.
So again, starting with the innate immune system, right? With the innate, there was some type of damage, right? Because of this bacterial cell, it caused the release of endotoxins, which caused what? A massive release of inflammatory cytokines, right? Such as all of these ones that we've already talked about here.
What is the overall result of these guys? One thing that they're gonna do is they're gonna act on smooth muscle cells and cause vasodilation, which increases blood flow and causes heat and redness. They're also gonna act on the endothelial cells, causing contraction, right? This is gonna cause a lot of fluid to leak out, increasing permeability.
And a lot of fluid leaking out can compress on the pain receptors, and variety kinase can activate pain receptors, inducing pain. That fluid exudate that leaks out can cause swelling.
So that covers swelling, pain, heat, and redness, which are the four cardinal signs of inflammation, right? And if there's a really, really bad form of inflammation, like you burn your hand to a third-degree burn around your hand, it actually can cause a lot of inflammation around this joint to where you can't move it, right? It's not your joint immobility.
What else can happen? These histamines and all these other chemicals can also cause the production of certain types of cell adhesion molecules. We've already talked about these in great detail; there's no need to go over them again.
These things could be like P-selectins, E-selectins, ICAMs, and VCAMs. What is their whole purpose? To enhance the margination response. In other words, cling to the edge of the capillary bed and roll on the surface, right?
Then, as it rolls, it can move through the actual endothelial cells by diapedesis, which is that amoeboid motion. Then, it can actually migrate to the site of injury where all these bacterial molecules are due to these inflammatory chemicals, and it's gonna move towards that area by positive chemotaxis, right?
So that's the overall result there.
What else can happen, though? A lot of these inflammatory cytokines that are also being released, like leukin-1, tumor necrotic factor-alpha, and interleukin-6, what can they do? Let's follow it up here.
Look what they can do. They can cause fever within the hypothalamus, right? They can cause the liver to produce C-reactive peptide, which is a good indicator of active inflammation. They can trigger the bone marrow to make more leukocytes via leukocytosis.
That's the entire inflammatory response for the vascular and some of the cellular effects, right? So it's not that bad right now.
What else can happen? Well, once these phagocytes get out here into this area and they start fighting with this bacteria, what can be the result? Phagocytosis. They eat the bacteria, right?
So they take the bacteria in through their pseudopods. I'll just call it phagocytosis. Remember, they form the phagosome, combine it with the lysosome, and break them down through the lysosomal action.
But neutrophils, sometimes depending upon how intense the bacteria or form a microbe may be, it might have to do free radical reactions called oxidative burst or release its chromatin out into the extracellular space to tag bacterial molecules for destruction.
For example, cut deep, Sanji.
What else can happen? The macrophages can phagocytose those actual bacteria and actually expose those antigens on the cell membrane with MHC class II molecules, major histocompatibility complex type II.
But remember, all nucleated cells in your entire body express what's called MHC class I molecules. So that's important, and we'll talk about it when we get to adaptive.
All right, so that's one mechanism there.
What else can happen? Remember, you also have complement proteins. Your liver is constantly making these complement proteins, and they're circulating within our plasma in the inactive form.
Whenever they're in the inactive form, what can happen? Whenever they actually act, they become activated due to certain types of chemotaxis or due to the increased permeability or due to the Fc portion of antibodies, so on and so forth.
What happens? You activate these proteins, and they undergo specific cascades, like the classical pathway, which is antibody-mediated, right? So it has to be antibody-mediated. Then it starts with C1 and goes all the way to C9, producing C3 and C5a, which enhance inflammation.
The alternative pathway is not antibody-mediated; it's directly binding C3b with the foreign pathogen, and that causes that whole process again, right?
Then, lectin just needs a mannose and lectin binding mannose to trigger this entire cascade.
What's the overall effect of these pathways right here? To produce the membrane attack complex to initiate lysis of the bacteria or to enhance opsonization by C3b or to enhance the inflammatory response to C3a and C5a.
So that's the complement system, still in the innate.
Now, what else? We also said, what if we have these cells here, our macrophages or general tissue cells? What if they're infected by a virus?
So they're infected by some type of viral molecules, right? If they're infected by the virus, what can happen? They can activate genes to produce specific types of molecules called interferons, like alpha, beta, and gamma.
What do alpha and beta do? They come over here to a nearby healthy cell and tell those nearby healthy cells to produce antiviral peptides, for example, protein kinase R.
What does that do? It actually destroys the actual virus or prevents the virus from attaching, right? And prevents this virus from causing damage in these tissue cells.
What does gamma interferon do? Well, the only one who really secretes gamma interferon is, because we have them over here, remember? Alpha and beta interferons are produced by tons of cells, a lot of different cells.
Beta interferons are usually specific to making platelets, though, upfront; they're made by platelets, right? Gamma interferons are made by specific types of cells, like your natural killer cells, your lymphocytes, your macrophages.
What do those gamma interferons do? We already showed it over here, right? These gamma interferons, secreted by macrophages or natural killer cells or lymphocytes, come over, activate other macrophages, and then do what?
Cause these macrophages to proliferate, get bigger, get hungrier, and increase the expression of class I and class II molecules, all designed to enhance the inflammatory response, right?
Then what else? Alpha and beta can also cause the activation of natural killer cells, who can come in and start killing some of these virus-infected cells.
So it's a beautiful thing, right? And that is a part of our innate immune system still.
Now, lasting for our innate immune system, we have these toll-like receptors. In these toll-like receptors, we have 11 different types, right? So many different types, but there's 10 that we're only talking about here because we don't know the function of toll-like receptor 10.
What is the overall result of all these? Because they're all responding to different types of pathogens, the overall result is the production of specific types of signaling proteins for chemotaxis, right?
Or the production of interferons like alpha, beta, and gamma interferons, and the production of tumor necrotic factor alpha, interleukin-1 beta, and interleukin-18.
And remember, these guys have to be acted on by caspases to become in their active form because then they're their preformed, right now, or their proform.
What do all these guys do? They enhance the inflammatory response, enhance chemotaxis, and try to be able to eliminate the foreign pathogens from the body, right? That's the desire.
Now, then we go into adaptive immunity.
What was the adaptive effect? You remember we took these macrophages with the MHC class II molecules, and we also took these free antigens, and we took them into a lymph node.
Well, what was the effect here? So again, what do we do? We take this macrophage, and we take these free antigens, and we bring them to the lymph node, right?
Because we already went through the phagocytosis process, and we know that the neutrophils exocytosed those free antigens. The macrophages are good antigen-presenting cells, those as well as lymphocytes, and specifically antigen-presenting dendritic cells.
They come in, and what happens? Let's see if we follow the free antigens first. The free antigens are the exhaustion as antigens bind onto a naive B lymphocyte, activating that B lymphocyte, right?
That B lymphocyte then can bring in the receptor-mediated endocytosis, bring that antigen in, and produce MHC class II molecules against it, right? And expose it on the membrane surface.
But that activated lymphocyte, which also has all these BCR receptors specific to that antigen, he can't get stimulated to proliferate yet. Why? Because he needs some type of stimulation from other cells.
So what's those other cells? Remember the macrophage? The macrophage is gonna be coming over here. It's having its MHC class II and the foreign antigen. It brings it to a naive T cell, T helper cell, right?
That T helper cell will have CD4 positive proteins. It will have a TCR, our T-cell receptor, specific to that foreign antigen, which will interact. When they interact, it activates a CD3 molecule, which sends this primary signal into the nucleus.
There will also be co-stimulation signals between B7 and CD28, and then there will also be the secretion of interleukin-1.
What does this do? Interleukin-1, that third signal, will activate this T helper cell to produce interleukin-2. And there will also be the production of interleukin-4 from other cells, which will bind onto this actual T helper cell.
Then what will happen? Whenever this interleukin-4 and interleukin-2 bind, it triggers the naive T cell to start proliferating and becoming specialized and differentiating into what's called TH2 lymphocytes.
Because remember, interleukin-4 converts the naive T cell into TH2, and interleukin-12 converts the naive T cell into TH1 or T helper 1 cells.
So now our TH2 cells are activated. They're ready to start producing specific types of interleukins. What are those interleukins? One of them is interleukin-4, interleukin-5, and interleukin-6.
And interleukin-4 is the very signal that these activated lymphocytes need to start proliferating.
What does that proliferation call? It's called clonal expansion, and you're making all these B cells with the BCR specific to that foreign antigen that we've started with this whole process.
They expand. Interleukin-5 stimulates these actual activated B cells to undergo differentiation.
So again, what does this step right here call? This is actually differentiation.
So differentiation right here will convert these actual B cells into memory cells or plasma cells. Memory cells will stay in our body for a while, right, with that specific B cell receptor specific to any foreign antigen.
The plasma cells will respond to interleukin-5 and interleukin-6, and they'll produce antibodies.
And what will those antibodies do? These antibodies can either do a couple of different things, right? We talked about it very briefly. They can bind with these foreign antigens and cause neutralization reactions, precipitation reactions, lysis, and we also said agglutination reactions, too, right?
So there's a lot of different opsonization. We'll go into more detail on those in antibodies, right?
All right, so again, they can undergo the opsonization reactions.
Now, that whole thing that we talked about is humoral immunity.
What is humoral immunity? It's the effect, again, one more time, of those exogenous antigens stimulating these actual B cells or these T cells, and the overall response is to produce antibodies in response to that, right?
Or to produce memory B cells. And we can also produce memory T cells. I didn't talk about those enough, but again, these are effector T cells.
But you also can make, as a response to this, whenever they proliferate, you also can make memory TH2 cells, and those memory TH2 cells will have a TCR specific to that foreign antigen.
All right, whenever the MHC molecule comes back, MHC class II molecule and the foreign antigen on the macrophage comes to him again, he'll be ready for it.
All right, that's humoral immunity.
What is cell-mediated immunity? Cell-mediated immunity is due to the... it's going to be exerted by these cytotoxic T cells.
And the cytotoxic T cells, they're gonna act on cells that have already been virally infected. So they've been infected by a virus, and there's no turning back, or they're cancerous.
What's the overall result? Again, one is it can actually downregulate the class I molecules, or it can produce the expression of a viral peptide that combines with our own self-peptide.
And then what happens? Our cytotoxic T cells recognize those either foreign peptides or they recognize the lack of class I molecules, as there's not that many.
And then what will they do? They'll produce perforins, which would create holes in the membrane, and granzymes, which initiate this apoptotic mechanism that we talked about, right?
So that's killing the cell.
Why is it cell-mediated, though? Because the actual infectious pathogen is already inside of the cell. It's not outside of the cell; it's inside of the cell, and it's affected it inside of the cell.
Okay, that's the basic way of understanding cell-mediated immunity.
We also talked about natural killer cells, but remember, just because I included them with the adaptive immune system, that doesn't mean they are a part of them.
They are not a part of the adaptive immune system; they're a part of our innate immune system. They're not specific, but their mechanism is very similar to the cytotoxic T cells.
How do they do this? What do they do? There's three mechanisms. One is they either recognize that there are no MHC class I molecules present, and if there are no class I molecules present, they perceive it as foreign because all nucleated cells have class I molecules.
Then what will they do? They'll produce perforin and granzymes and kill the cell.
They'll also recognize an abnormal form of the MHC molecule, right? And again, we said MHC molecules have alpha 1, alpha 2, alpha 3 chains, as well as a beta 2 microglobulin.
MICA has no beta 2 microglobulin, so therefore, he's kind of like an MHC if he's recognized. But the natural killer cells, they'll actually release perforins and granzymes and kill him.
And then again, if there's any type of foreign antigen with IgG antibodies bound, the natural killer cells release perforins and granzymes and kill him.
Again, guys, this pretty much gives us everything we're going to need to know about the entire overview of what the adaptive and the innate immune system.
All right, ninja nerds.