Video 1: Branches of Immune System
So, uh, welcome to the lecture six of this immunologic course and myself Agnew Ganguli and, uh, I will be also. Teaching you some parts of the immunology course along with . So, uh, we will start discussing about the, uh, whole network of the, the immune network. And we will start discussing with the innate immune system. So what is the it immunity and how does the unit immune system works? So before we start with the discussion about the innate immunity, uh, let us try to understand how the different branches of the immune system actually, uh, works and how the coordinates. So whenever, let us say whenever there is an innovation in the body, what are the initial barriers that a pathogen has to cross? So initially whenever there is a tissue damage or an invasion. So the first barrier a pathogen would come across is, uh, the anatomic barriers, for example, like the scheme, the mucous membrane, so that it will not be able to penetrate. Now, if it crosses these kind of anatomic barriers, Then it has to face the physiological barriers. Now the physiological barriers clearly includes, uh, certain, uh, very important things that we come across. Whenever there is a infection, you see a rise in body temperature, so the body temperature rises so that most of the pathogens, they do not survive in this temperature and the acidity of the stomach. For example, So the stomach is highly acidic. So most of the pathogens, they do not survive there. So this is the second barrier that is the physiological barrier. And then there are many other chemicals, chemical mediators, which also immediately come into play and try to restrict that pathogen from attacking our body. So this is, uh, kind of, uh, uh, physiological barrier. And then we have the phagocytic barriers. So now the phagocytic cells, that is the cells of our immune system. The th the very important cells of our immune system are the phagocytic cells. They will immediately come into that site of action, and they will now try to engulf those pathogens and kill them. So the clear the pathogens from the system. And finally, you can have an inflammatory response. An inflammatory response means you will have, uh, some mediators of inflammation that are being released, and then you will have swelling, redness, and many other acute inflammatory skin, uh, symptoms, uh, that will immediately start. So this entire thing that, uh, occurs in the, uh, the very first phase of an pathogen invasion or an immunological challenge, these are all from the innate immune system. The innate immune system is the first line of defense of the body. When this innate immune system cannot clear the pathogen. Or let us say that it is new for the body. So the body has never seen that pathogen before. Let us put it in this way. So in that case, the innate immune system will not be able to clear the pathogen. And now its job is to transfer the signal from the inlet to the adaptive system. That means the cells of the adaptive system, the who are the adaptive systems cells, the cells of the adaptive system are the D and the billing for sites. So the signal will now be transferred from the eNett system to the Arab PIP system. And now the T and the B cells will be activated and we will have either a T-cell mediated response or a humoral response. There is a B-cell mediated response. So this is kind of a very well coordinated network. So initially the unit system tries to fight the pathogen. With all its uh, possible, uh, weapons and its weapons and mostly the phagocytic cells, uh, various chemical mediators compliment system. Uh, we will discuss all these things in details. Uh, Later on one by one. So the compliment systems, the cytokines, there are many, many, many chemical mediators, uh, which are working in the unit system. So they will try to clear the pathogen first. They will try to clear the infection. If it fails, it will transfer the signal. To adaptive immune system and this signal transfer primarily occurs via some antigen presenting cells. Now, the name you can already understand from the name that they are presenting the antigen. So they are antigen presenting cells. They will, in some way, they will try to present a new antigen to the. Adaptive system. And then the additive system cells will get activated and either they will produce antibodies like from the B-cells or they will activate the T-cells and will kill, uh, those patterns.
Video 2: Basics of Innate Immune System
So now let us see, uh, how this immune innate immune system actually works. If you look into the board here, so you see it here that whenever there is an infection or a tissue damage, There are bacterias or pathogens that are coming into the site of action. So these, these green ones, these are the bacterias, for example. And if we consider this as the bloodstream, this spot, this is the bloodstream. So the blood is flowing and many immune cells, the cells of the immune system, they are present here, like the mosque cells, the neutrophils. And, uh, there, the neutrophils, the mosque cells, they are all present here. So now these cells will start immediately. They will start to migrate to the site of action. How will they migrate? There is a specific mechanism by which this cell starts to migrate to the site of action. And then you have tissue. Macrophages the macrophytes cells. There's the tissue macrophages that are already present the tissue masters. These are already present there. So now these cells, which migrate there, we'll try to engulf the pathogen by a process called Fango cytosis. And the first cells or the immediate acting cells, which immediately go to the site of action are this neutrophils. So the neutrophils are kind of the first. Acting cells of the immune system. That means they are the fastest acting cells and they immediately go and try to engulf or phagocytose the pathogens or eat them up. Other than that, there are also some other chemical mediators and chemical proteins, which actually. They mediate this migration. That means they, they try to attract more and more of the cells of the immune system to go to the site of action. They are, for example, the chemokine ones. We will discuss them in details later on just for the time being I'm just using the terminology. So, Like, for example, the chemokine ones, there are other, uh, mediators as well. So this chemical molecules, they are chemo attractants so they will attract more and more of this cells of the immune system. Like for example, the neutrophils, the cells, they will move to the site of action. And then there are a lot of signaling going on in this region. We are not discussing them in details right now. For example, this mask sense. What are the muscles do? The muscles they contains granules inside them. And these granules are full of histamines. So whenever there is an infection, for example, the histamine released and this release of the histamine, one of the primary action of the histamine is. To do vaso dilation and increases the vascular permeability. So it increases the vascular permeability and then why that is why it allows more and more of this. Cells of the immune system to migrate to the tissue. So by that more and more of those neutrophils, the macrophages more muscles, they moved to the tissues and there are also the tissue Dendright excels present here. This dendritic cells are one of the most important cells of the immune system. So these are the dendritic cells. So what do these dendritic cells to the dendritic cells has all very, very important role to play. The dendritic cells are actually. One of the major cells that connect the init system to the adaptive system and the macrophages as well. So these cells, primarily the dendritic cells and the macrophages, they are also known as the APC or the antigen presenting cells. So they present the antigens.
Video 3: Recognition of Foriegn Pathogens
Now, how do they do that? So, as I described here, if you look into the picture again, There is a insect bite or a tissue damage or a nail piercing the tissue. And then there are bacterias coming in. Now these bacterias are, uh, the, the initial, uh, function of the immune system is to send the cells or the phagocytic cells to this region of infection and leading to, and Gulf meant of the bacteria. So the bacterias or the pathogens that have interned are engulfed. By the phagocytic cells. And then, uh, there is also a release of histamine from the granulocytes like the muscles and leading to vessel dilation, vascular permeability increase and leading to migration of more of these cells, more of these cells going or moving to the site of action. No. How do the cells of the immune system, they actually recognize these bacterias or the foreign pathogens? So there is a specific, uh, feature on the surface of the bacteria. Describe us B a M B B E M P, which is also known as pathogen associated. Membrane patterns, patterns. Now these patterns are recognized by specific receptors, which are known as pattern recognizing receptors. So these are the P R RS. Now these feet are ours. They can recognize these pathogen associated membrane patterns on the surface of the pathogen or on the surface of the bacterias. So one of those specialized cells who can recognize this be MPS are for example, the macrophages. And there's macrophages. So let us see what exactly a tissue macrophage is doing in this situation. So let us say, this is a tissue macrophage and this tissue macrophage expresses on its surface, a receptor specific receptor, or this PRR kind of receptor, like the toll, like receptor the TLR. And this toll, like receptor is one of those important receptors, which can recognize the PA MPS, the PA MPS that are present on the surface of the bacteria. So here you have the PA MPS, which are recognized by the toll like receptors. And then there are also the compliment receptors, the CRS. So by virtue of these complement receptors and the toll, like receptors, these macrophages, they can recognize the foreign bacterias. Now what happens there is a process called endocytosis. So now it eats up the foreign pathogen or the foreign bacteria. So it has been eaten up by that. Macro fudge. So, and it is being internalized. So then the process is called Fagel cytosis and it has been eaten up and the bacteria is then internalized. And this is called a phagosome. What is formed is called a Fargo soon. And then inside the cell, there are acid compartments, which are known as de lysosomes. Yes. So the next event that occurs immediately after this cell eating is a fusion between this phagosome and de lysosome. Leading to the formation of a phagolysosome. This is called a Fagel Lysa zone. So now this phagolysosome is being formed, which contains this bacteria, which is being internalized and no. It degrades the foreign pathogen and degrades all its components, like the proteins, the carbohydrates, everything that has been internalized, everything is being degraded and chopped up into small pieces into small peptides. And these small peptides are then displayed on the surface. They are now being displayed on the surface of they are displayed on the surface of the macrophages. These peptides are these bacterial peptides. They are now displayed on the surface of the macrophages by a specific class of MHC molecules and do, which is actually required for transferring the signal to the adaptive system that is for activation of the T and the B cells. So, this is what this enter event that we described in this part here actually shows it for our tissue macrophytes. Now this macrophage is now is an activated macrophage. So it is activating. So it is an activated macrophage. Now, what does this activated macrophage do? This activated macrophage actually does a lot of things. So this same thing we can see also in case of Arden, right Excel. So the den right Excel is also an antigen presenting cell. And whenever there is this kind of a response, the den writing cell is also able to internalize or phagocytose bacterias and pathogens, and they can also present on their surface, duh. Peptides process peptides from those bacterias or from those pathogens to the cells of the adaptive system and this den right. Excels by a process called licensing because normally the dendritic cells, they cannot enter into the, or these antigen presenting cells. They cannot enter into the adaptive system. So whenever. There is an immunological challenge. And in it system, first, try to face that immunological challenge. Try to clear the pathogen from the system. If it fails to clear the pathogen from the system, it starts a process usually by help of this antigen presenting cell, it starts phagocytosis primarily by. Antigen presenting cells like macrophages or the t-shirt and writing cells. Now this generating cells and the macrophages, they then go to the lymph nodes. And by going to the lymph nodes, they're the meat, the B cells and the T cells. So there are the T cells and the B cells, but these are naive. That means they have not yet met any foreign pathogen. So these are the nine 50 and the B-cells that are usually present in the lymph node, waiting for the signal to come from the antigen presenting cells and from the inner eNett system. And then they are activated and, uh, then antibodies are produced and other humeral responses and other cell-mediated responses are triggered.
Video 4: Cytokines
So, Let us see, uh, what happens in this part. So now this activated macrophage, the macrophage, which has already internalized or already phagocytosed a bacteria or a pathogen is now activated. And inside that leads to in the, in the nuclei that leads to. Expression of certain genes. So there is gene expression. So there is expression of certain genes leading to secretion of a class of molecules, which are known as the cytokines. Cytokines are a very, very, very important effector molecules in this immune system. So they are the effector molecules of the immune system, and they can do a lot of functions. They can do a lot of functions, uh, by activating the. B cells and the T cells, they can do many other functions. So we will discuss about this, uh, cytokines in specific classes and this cytokines and the downstream signaling can also lead to the secretion of another kind of protein, which are known as the compliment proteins. So, what does this cytokines actually do? This cytokine can lead to, or they can attract more leukocytes. To the site of action. As I told before, they can attract more leukocytes to the site of action. So for example, the chemo kines, which is also a class of cytokines, so they are also involved in attracting more of these, uh, cells to the site of action. They can stimulate the liver and lead to secretion of a specialized proteins, like the compliment proteins. they can also lead to a fat hypothalamus leading to rise in body temperature. So you have fever for example, and they can also activate. They can also activate the T and B cells. So the cytokines has varying roles in the, uh, downstream, uh, in the downstream pathways. So the cytokines are one of the major effector pathways. So if we, uh, look into this whole picture again, very carefully, the innate immune system. Starts with the immediate invasion of a pathogen in our body. As soon as it crosses the anatomical barrier. For example, there is a, uh, nail piercing or an insect bite, and the pathogen enters into the, uh, uh, into the tissue. And then there are the cells of the immune system. Primarily the neutrophils, which are the first acting cells of the immune system. And they are very fast. They go to the site of action very fast in our next lecture, we will describe how, uh, the cells of the, uh, I mean the neutrophils, they move very quickly to the site of action. So, and then there are the antigen presenting cells. We have the antigen presenting cells, the macrophages and the dendritic cells. And you have the mast cells, also the mast cell. So the, and then immediately there is release of histamine, which leads to vassal dilation, vascular permeability, increasing the vascular permeability, leading to opening up of this high endothelial venues or the ATVs. Does facilitating more migration of more of the neutrophils and the other cells of the immune system to the site of action. At the same time, there is phagocytosis initiated by the tissue macrophages, and this is primarily initiated. By the pathogen associated membrane patterns that are present on the surface of the pathogens, which is recognized by some specific receptors that are present on the surface of the macrophages. So the macrophages by this presence of their toll, like receptors, they can recognize the pathogens and then they can internalize or eat them up. Once they internalize the pathogen. Then it forms the phagosome, which then fuses with the lysosomes and forms the Fagel Lysa zone and inside the fabulist zone, the pathogen, uh, is kind of degraded in all its uh, protein carbohydrates, and all the components of the pathogen is degraded and chopped up into small peptides. Now this small peptides are then displayed on the surface off. The macro fudge on the surface of the macrophage by specific classes of MHC molecules. And this has been primarily required for activation off the adaptive system. So now this antigen presenting cells as the name, uh, is given because the present antigen. So now the present this peptides. Or these antigens to the cells of the eruptive system that is the BN, the T-cells, and activate them apart from presenting antigens in the, this an activity tissue macrophage also secretes a certain class of proteins, other effector molecules that are the cytokines. Now the cytokines have varying function and they Can do a lot of functions of which initially they try to attract more leukocytes into the site of action. They activate the liver, thereby producing proteins and primarily the compliment proteins. The compliment proteins are also very important in the unit system. We will describe compliment proteins in our, uh, upcoming lectures and then, uh, leads to rising the body temperature. So you have fever. And also tries to activate the T and the B cells. So this is kind of an overview that we discussed today and try to understand how the immune system initially tries to respond to our tissue damage and an attack by a pathogen, a foreign pathogen, and leading to, and then it starts to generate an inflammatory response. What we call an inflammatory response. So, and that is a complex process and influence inflammatory response involves a complex process, starting from migration of more and more of the neutrophils, more, uh, ma uh, degranulation of the muscles release of histamine and, uh, release of other, uh, mediators of inflammation. So we will, uh, slowly, gradually, uh, look, uh, what exactly. We mean by inflammation and how exactly it is mediated, uh, by this, uh, specialized cells of the immune system.
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