 Welcome back to the NPTEL lecture series on analgesiology. So, we are in section 6, where we are essentially dealing with the blood cells, immunity and clotting. So, I give you an introduction by introducing the topic with red blood cells. Then, we talked about the clotting factors involving platelets. Then, we talked about how these different blood cells, the red blood cells, white blood cells, platelets are originated. What are the different components of blood in terms of plasma? Plasma component, which is the fluidic component with suspended proteins, electrolytes, organic molecules, organic waste, which the blood collects all the time and dump it out. Then, we talked about the formed element in the form of the different cell types, which are present there. In the case of the genesis of the blood cells, we talked about how from the stem cells, there are two sets of cells, which are the myeloid origin and the lymphoid origin. From the lymphoid root, it leads to the formation of the lymphocytes, which are one of the white blood cells. In the myeloid tract, it leads to the formation of RBCs, platelets from mega karyocytes, the breaking down of the mega karyocytes or the fragmentation of the mega karyocytes. Then, we talked about the formation of neutrophil, which is a white blood cell. Monocyte, basophil, eosinophil. So, these different names of white blood cells, what they got, eosinophil, basophil, neutrophil, how they got all these names. Today, what we will do? We will talk about the white blood cells. Once we have done with the white blood cells, our next objective will be to understand about the blood grouping, how the blood grouping takes place and what are the influence of blood grouping. In between, we will talk little bit after once we finish the white blood cells. We will talk about the different forms of immunity. That is all we will be covering in that part. We will not go in depth with immunity, because that is outside the purview of this course. So, we will just touch upon the base. Restive people can really, if anyone of you is interested, I can suggest some of the books through which you can go through those books. That will give you a much detailed study of immunity. So, coming back to the white blood cells, we have already discussed the white blood cells have two sets of origin, myeloid origin and a lymphoid origin. So, cross white blood cells and white blood cells as I told you, I have already shown this layout lymphoid origin and myeloid origin. Within myeloid origin, you have four different types and here you have lymphocytes. I told you that lymphocytes from T cells, from V cells and it from NK cells, which is also called natural killer cells. So, this is natural killer cells. I did not show you in the last, the whole flow chart of the genesis of the blood and specifically with respect to white blood cells. On the myeloid origin, we will be talking about the neutrophils. Neutrophils, eosinophil, basophil, you have monocytes. Typically, if you take one microliter of blood samples, typically you get around 6000, 7000 odd white blood cells, which is distributed among these five different cell types, neutrophil, eosinophil, basophil, lymphocytes likewise. So, what are the functions? First of all, we will talk about what are the different functions of the and what are the different features of these white blood cells. One of the features of these white blood cells, I have already shown you, they are kind of huge size and they are also called polymorphonuclear. Poly means many morphological features nuclear. So, morphologically, they have multiple nucleus. So, whenever you see under the microscope, if you do a smear and you see, essentially they look like more like one second. Save this, they will mostly they will look like this. This is what is meant by polymorphonuclear. Poly, many, morpho, the look morphonuclear. These cells have a very interesting features. You see this huge cell out there. These cells can change their shape. They can show a lot of amyboid kind of women. You have heard about amyba. It is one of the lower organisms. You know, they change their shape, they move through. So, in other word, what happens? It is like, let me give an example. I mean, something like, which is a sponge kind of. So, if the vessel size say for example, it is flowing through a vessel of this diameter, then the vessel size goes a smaller. So, they change their shape. They become more like elongated. So, in other word, they have the feature like this. Suppose, say for example, they are traveling through the vessel like this and then the vessel becomes like this. Essentially, they change their shape and they become, their new shape becomes something like this. They will travel. So, they show something called amyboid movement. This is one of their classic feature. They have an amyboidic movement, which could be observed. The second thing, they have the ability to move out of the blood vessels, because if they cannot do so, then they cannot reach the site of, as I have already told you, they are involved in immunity. So, that is the major function. So, for the immune action, suppose say for example, you draw it, that will make a portion. So, for example, you have a blood vessels out here and you have a pathogen sitting out here somewhere, which is significantly distant from the blood vessel. So, what these cells will essentially do is, they will start moving towards it. They will come out of the blood vessel and they will start moving towards it and this movement of course, since they are moving. So, this is where the pathogen or the infection is sitting and these are your WBC streaming to the site of pathogen and here you have the blood vessel, where the blood is flowing. So, they have the tendency to, they have the ability, tendency is the wrong word. They have the ability to come out of the blood vessel and move to the site of infection or site of injury, where they are being needed. So, having said this you have to realize, if they have to come out of the blood vessel, if you remember, while I was showing you the structure of the blood vessel, their form of the endothelial lining. So, if I had to blow up this image, what I drew for you, if I blow up this image, so the blood vessel structure will be more like this. You remember, I talked about fenestrated capillaries and all those things. So, there is a very little gap out here, very teeny tiny gap from which something can come out. So, for a cell like this, which has to come out through this, it has to change its shape significantly. It may have to take a shape like this before it can come out. So, that is the reason why I highlighted this point, that they have a tendency, they have the ability. So, in other words, if you have to change the shape that much, it means the cytoskeletal protein, which is making the framework of that cell is different from others, because you are squeezing your shape. They are very, very smart cells, they are changing their shape like this took like this, like this elongated, they can pierce through, they can move through. So, these are very, very smart structures, which can modulate their shape based on the situation. And this is one of the hallmark of these cells, second thing. So, say for example, they have to reach to the site. So, here is a white blood cell and it has to reach somewhere out here, here is the pathogen is almost. So, these cells have the tendency, just like the transmitters, you know, you receive signal, some signals are coming. They could receive the chemical signal and they have a tendency to a positive or a negative chemotexas. Chemotexas means you are moving towards something in response to a chemical. There is a chemical sitting here and then it is sending out some kind of stimulus, which could be sensed by these cells and they start streaming like this, as if the army gets a signal and then from a GPS they get a signal. There you have to attack and the army started crawling through there to that site. So, this is how they move and this is very, very tightly regulated and this is something amazing, the way they move to the site. And then they could, you know, kind of, you know, imagine and think of a very old city, where there are lot of alleys, lot of roads and through which the army is moving through, something like that, just the way they, you know, crawl through. Those of you have seen like, you know, some movies like, which I can give you a day to day example, like those who have seen Black Hawk Down. If you see the city of Mogadishu and they are moving through all those, you know, curves and crevices of a city, exactly the same way. The white blood cells have the ability to move through and go to the site and capture on to the pathogen and if they fail to do, so we won't be alive. So, this is one of their, so they have this chemotaxis kind of process. They could really crawl through, they could move to the site and they can sit on or they can, you know, surround the location of infection or pathogen whatsoever. So, from here what we will do after explaining this, we will talk about the role of this individual WBCs and why they got this different name, why we called eosinophil, why we called basophil, why we will call neutrophil. So, then genesis and there, then some informative stuff that what is the general number you see. So, whenever you see a blood report, you should be able to, you know, figure out whether eosinophil has gone up or basophil has gone down and whatsoever and so on and so forth. So, now, let us get back to the details of some of the, these different cells. So, we will first start with neutrophil. Neutrophils are bigger than others and basically 50 to 70 percent of the total WBCs of the total WBC is neutrophil. So, these are basically the, if you break this word, this neutro means they are neutral, neither they are acidic or neither they are basic, they are chemically neutral. So, basically you cannot stain them, neither with an acidic dye or a basic dye, why they are dye. So, this is something just slightly of the, I am digressing. So, whenever these dyes works, because most of the, like almost pretty much the whole biology depends on dyes, imaging, you have to imagine. When you see something, you believe it, if you do not see, you will not believe it. So, the biology over the years have evolved, have dependent enormously on imaging, has dependent enormously on different dyes, different fluorophores, different chromophores and everything. So, this chromophores, fluorophore dyes, they work with very simple basic principle. If there is a basic component, the acidic dye will go and bind, if there is acidic component, a basic dye will go and bind or if there is a neutral thing, then you needed a neutral dye. So, since these cells are neutral in nature, they do not, I mean chemically they are kind of neutral, all their. So, it is really tough to stain them with any basic or acidic dye. But, mind it, these are probably the biggest one among all of them and they are in highest number, one second back to the. So, this is basically, they look more like, this if you see, then it will be like. So, this is pretty much how they look like. And they support in different kind of, they have several functions, they are highly mobile, this is one of their feature, they are highly mobile in nature and they are the first one. They are generally the first one to reach the injury site. So, in other word, they are the first one, which basically, reach to the site and the first thing they do, they engulf all the bacteria, they have a tendency to engulf the bacteria inside them, which I was showing you one time, they go to the site like this and if this is the bacteria which is sitting there, which has to engulf. So, what they will essentially do, they will just take it inside them like this and then they will destroy it. And they destroy it using different chemical means, I will come to that. So, they do it by sometime by hydrogen peroxide and all those things. So, they secrete, they have granules which secrete hydrogen peroxide and kind of destroy this different bacteria. So, this is one of their major function. Then next come, eosinophil. Eosinophil got its name, because it binds to eosin dye and which is dark red in color and it is basically acidic in nature. And if you see it under the microscope then eosinophil will look red all over the red, because the eosin is red and it is acidic in nature. That is why it is called eosinophil, eosin dye. So, just like the neutrophil, they are also of the same kind. They have the tendency to engulf, go to the site of infection, site of injury, engulf the pathogen or surround the cell or damage cells or something and you know destroy it, chop it down by engulfing it inside their body. They are huge. They are smaller than neutrophil, but they are significantly big. Then comes the next one which is called a basophil. Why it is called basophil? Because as the name indicates, as the name says these are called basophil, they bind to a basic dye. This is the tendency. That is why they are called basophil and these are approximately 8 to 10 micron big. Whereas, eosinophil, they are of the same order, but slightly smaller than the basophil. These basophil are the basically the way they look like, they will look mostly in a blood smear. If you look at it, it will look more like pink color. This is how they look under the microscope if you kind of see them. So, these have the tendency. They contain histamine and heparin which prevent blood clotting. We have talked about this. So, these basophil contains heparin and the histamines. So, the heparin as we have already talked in the clotting. They are anti clotting agents. They help in preventing clotting. So, in other words, they ensure the viscosity of the blood remains constant. Talking about histamine, histamines are the molecules which are secreted whenever there is an inflammation in the body. So, if you see some people take like anti histamines. Anti histamines are given to ensure that those inflammatory. These are mostly cytokines, histamines. So, these histamines whenever there is an inflammation, there is some say for example, somebody have asthma. The histamine level goes up or some kind of attack of pathogen. Histamine level goes up. So, sometimes anti histamines are giving and these histamines are secreted by these basophil cells. From here, we move on to the next one which is called the monocytes. Monocytes are approximately 15 micron in diameter, which is essentially 2 times the diameter of R B C. Two times greater than the diameter of the R B C. These remains approximately for 24 hours in the blood vessel. That is pretty much and they also follow the same function as followed by the neutrophil. They reach to the site. They engulf the cells and they destroy it. So, these different cells contain different kind of granular structures. Some contains peroxide granules, which is the neutrophil. Some contain histamine granules. Then, heparin granules and they have different roles in clotting, in defense. Some of them contain peptides like defenses. Neutrophil actually contain defenses. This is a small peptide help in the defense mechanism. So, all of them are equipped. The arsenal of our immunity is equipped with wide range of small molecules and they have complementary role to play whenever our system is under threat from any kind of pathogen, which is continuously. We are continuously under threat from the surrounding pathogen. These different molecules, these small molecules, which are contained and which are being synthesized by these soldiers, blood soldiers of our body. We are continuously responding to these different changing environmental surrounding and based on that, they act. They secrete these different compounds to help us to survive. From here, we talked about all the four different WBCs of the myeloid origin. Now, we will move on to the lymphocytes, which are from the other root, from the lymphoid origin. Among the lymphocytes, the lymphoid origin, they form the lymphocytes. The lymphocytes could be classified into three groups, coming to the lymphocytes, lymphocytes. So, lymphocytes are classified to T cells, B cells, B cells, and natural killer cells or NK cells. Sometimes, in short, they are called NK cells. So, the T cells are also called cell mediated immunity. I will come to that very soon, cell mediated immunity. B cells are responsible for humoral immunity and natural killer cells are responsible for immune surveillance. So, in other words, what is happening is, these T cells, which are involved in cell mediated immunity, these cells, just like the neutrophil, basophil, eosinophil, monocytes, move to the site of infection. At that site, they multiply, could surround the cells or they secrete certain compounds, which will ensure that the pathogen gets destroyed or they activate the other WBCs of the myeloid origin, which are reaching. So, it is most the direct cellular action at the site or on the pathogen. That is why it is called cell mediated immunity. Yet, there is another one, which is called humoral immunity. Humoral immunity is, there are a section of cells or lymphocytes, which secrete something called antibodies. That is where it starts the whole origin of antibodies. These antibodies go and of course, they do the same thing, just like other chemicals does. But, this antibody lead to the whole concept of vaccine development. What does that mean? So, that essentially means that, say for example, you are attacked by a pathogen for the first time. So, your body will of course, fight it out and during that process, those B cells will generate some antibodies in your body, which will fight against that specific pathogen. So, first time the pathogen attack, you are ill for some days and then you know the B cells and along with B cells, along with T cells, N K cells and the whole myeloid WBCs handle the situation. But, the body remembers it. How it remembers? Because, in your blood titer, there are very small number of those B cell antibodies, which are present against that XYZ pathogen. So, next time when it attacks, they are much more well equipped. It is just like you know attack first time, somebody beat you first time. So, you know the next time you know how to handle this individual. So, now the body is in a strategically much more sound position to handle it. So, that is why they say that you know, you should fell ill at times, especially in your childhood, little bit here and there sneezing, coughing and we should not give antibiotics or anything, because you develop your immunity. Let your B cells continuously you know charge up the system. So, you are always charge up. So, you know you have that memory. So, you know next time when it happens, you can fight it out. That form of immunity falls under this whole B cell or humoral immunity, where different antibodies are being form and that is whole subject in its own. The whole field of immunity and within immunity also, humoral immunity is I mean like one of the very well explored and very intense research is going on, on all these areas. Those are like kind of almost our life line you can call them, because we are always at war. So, if you understand that how these antibodies are functioning, it could help us a lot. So, talking about this, I told you that this is the genesis of the whole vaccine is this. So, basically the whole idea is that, so say for example, I wanted to create a vaccine. So, what I do? I take that pathogen x y z pathogen and I inject it into a system at a very very low titer, at a very low concentration, titer means that is a very very low concentration. So, automatically it will spark up the production of the B cell antibodies. So, now your system is pre incubated to face this disease and that is where, so for example, let me just draw it that will make sense. So, say for example, here is an say let us take the example of say one minute let me, let us take an example. So, this is an individual. Now, what I do that I take say for example, for disease x, it could be any disease, it could be chicken pox, a small pox or whatsoever disease x. So, I want this person to get an immunity against disease x. So, what I will do when this individual may be very young or infant or at a older age whatsoever, I know the pathogen for disease x and I know the level say for example, this unit will cause disease. So, anything less than x unit, so less than x fairly very very less than x will not cause any disease will not cause disease, but this amount which is say for example, equal to y this amount is good enough to activate the B cells. So, what I do I pick up this tighter and injected in this person. So, as soon as I injected into this person, the B cells which are needed the antibodies which are needed to fight against this disease fight against this disease gets flared up. So, now in the blood vessel in all his blood those specific B x antibodies are present there. So, whenever this disease comes this person is much more well equipped to fight against that disease. So, this is the whole game of antibodies and this is the whole genesis of the vaccine development where it all started and then rest is all history. Now, we all know there whenever a child is born the child are given lot of vaccine especially in the tropical countries which are most susceptible to the wide range of tropical disease for which several vaccines have been developed over the years is starting from Kalajar to influenza and everything there are whole series of vaccines which are there. So, in other word what you are doing you are tweaking the system you are just charging of this is kind of a charging mechanism it is a very clever mechanism though. So, people are trying to find out vaccine for AIDS which is currently one of them in the market people are trying to find out vaccine against malaria which is a very terrible problem in the tropical countries and little bit of subtropical, but mostly in the tropical countries. So, up and little bit up and little down along the tropical rainforest these are some serious problems could we find this. So, vaccine this is one of the hottest area where things are happening these are kind of happening zones then you have the natural killer cells these cells are as I told you these are surveillance they just just like a GPS they are moving around moving around there is a problem they keep on chemo tactically sending signals immediately the whole army started moving into that site fine you have to take care of it. So, after talking this about talking about all these different kind of WBC's and everything I wish to close in with two aspect the immunity could be classified in two level one is the intrinsic what we have in a in a. So, say for example, some of the thing is that our skins they produce a lot of peptides those are form of immunity different structures of our body they prevent the entry of the pathogen those are immune our immune systems there are several molecules several different kind of. So, those are all falling under innate immunity those are all under the classification of innate immunity and yet there is another form of immunity which is governed by these antibodies which is the other class. So, broadly speaking immunity could be divided into innate immunity and the other form of immunity which is governed by antibodies and the phagocytosis and all those kind of things. So, the major so this though this is not part of it the major receptors which are involved in immunity are called toll like receptors TLR's in short form this toll like receptors it is just like you have seen on highways you have this toll roots toll booths where you pay and you move just like that they are all over our body even including into the nervous system this toll like receptors ensure something which has not paid the money should not enter. So, pathogen is not going to pay a money to enter your system they try to you know try to fool this toll like receptors and move into the system. So, these toll like receptors and all these falls under innate immunity and then comes the rest of the immunity which is covered by all these different kind of cells. So, this is the overall though since this is not part of the part of this curriculum I just to give you an idea how this immunity could be classified. So, that is it innate immunity and the immunity what I told you all these different kind of cells which are involved with humoral immunity, cell mediated immunity then immunity offered by this cells from myeloid origin and everything and you cannot really very there is a zone where pretty much both the immune systems merge innate immunity I mean there is a overlapping zone. So, with this I will close in on this and the next class what we will do we will talk about how the blood groupings are being done and how that affects in the childbirth thanks a lot.