 Welcome back to the NPTEL lecture series on animal physiology. So, we are in section 6. So, we have covered 4 lectures and today is the concluding lecture on section 6 on blood cells immunity and clotting. So, as of now I have covered the red blood cells or erythroblast. Then from there we went ahead and talked about the clotting which involves all the platelets and the clotting factor, intrinsic factor, stringic factor, role of the endothelial cell and the surrounding tissue role of the platelet cells. Then we talked about the genesis by which all the different blood component or the formed elements of the blood, the red blood cells, white blood cells and platelets are formed from the stem cell origin. And in that process of course, we have discussed how RBCs loses their nucleus the whole process of 15 lipoxygenase, sharp rise of 15 lipoxygenase and followed by a fall in a very narrow time window. And then in our fourth lecture we discussed about the immune cells which are our white blood cells. We talked about the myeloid origin, neutrophil, basophil, yosinophil, monocytes and we talked about the lymphoid origin which is lymphocytes. And then among the lymphocytes we talked about the B cells, T cells and the natural killer cells and the origin of cell mediated immunity and humoral immunity and within that we talked about the origin of how all these antibodies are getting originated. And among the myeloid origin like monocytes, neutrophil, basophil we talked about the way these are being identified using acidic dye, basic dye likewise. So, today we will be concluding with one aspect which I purposefully did not touch. I told you at the end I will be going to touch that. That is we will talk about couple of disease and we will talk about the blood grouping. I have not talked to you about the blood grouping. How the blood? So, you must have heard that you know sometimes they say what is your blood group? Somebody say A positive, somebody say O negative, somebody say O positive or A B or B positive. So, what essentially that means what how we call it something A and a positive sign or A a negative sign O and then a positive sign. What are these groupings? This is one aspect what we are going to deal. Second we are going to deal that how that could influence the birth of a new child in terms of pregnancy. That is the second thing we are going to deal and the third thing what we are going to deal is what is jaundice? We hear about this you know someone is suffering from jaundice. What really jaundice is all about? Though I have covered a part of it in the first lecture while talking about the RBC and its degradation, but I did not go in depth on the jaundice what I will be doing. So, let us start with the blood grouping. So, essentially we know that you cannot like if somebody needs blood I just cannot draw my blood and put it in that person. So, the first thing doctor tells they check my group and they check the group of the recipient. What that essentially means? That essentially for a layman that sounds like my blood. So, when I am drawing blood basically I am drawing blood from my blood vessels. So, what is going to the other person has the formed elements which includes RBCs, WBCs and the platelets and all the electrolytes and everything the plasma all the fibrinogen and everything. So, if I cannot transfer like you know if I cannot just as it is put the blood to another person that means either the form elements or the liquid component has some signature and if that signature is not telling the recipient will not accept the blood. So, where lies the signature? So, to the best of our understanding what we have because this is another hot area where still work is enormous work is going on the signature lies in the red blood cells and what kind of signature is that. So, if you remember the first series of lectures when I started in the introduction I talked to you about the bilipid membrane of the cells every cells has a bilipid membrane. So, and there I talked about the presence of sphingolipids, colostrol and several other lipids and there also I talked about the glycolipids and glycoproteins the presence of all these things. So, just for the recap we talked about. So, let us take it back to the formally let us start the lecture. So, this is section 6 this is lecture 5 here we will be talking about blood group. So, now, talking about what I was trying to tell you. So, whenever I drew a cell I drew it like this. So, and I told you that this is the membrane boxed up and the membrane looks like if you go back to the first lectures initial lectures I spent significant amount of time on this and I told you that these. So, these are the lipid bilayer within the lipid bilayer I told you this they have these these are the polar heads these are the hydrophobic tails and these tails are mostly consist of fatty acids fatty acid tail they are water loving water hating tails. So, there I highlighted one point that these polar groups are modified with sometimes with carbohydrate sometimes with some other proteins and based on that there are glycoproteins and glycolipids. So, after giving this kind of you know giving me like kind of rehashing what I have already taught you it is in those lipid bilayers some of the signature lies those signature determines whether you will have blood group A blood group B or blood group O or blood group AB. So, let us first of all classify the blood groups first step after classification of the blood group we will talk about the antigen and antibody is against it and then we will come back and determine the molecular identity of this and then from there we will move on to the another factor called RH factor for which you get positive or negative sign with your with your any when the whenever the blood group is recruited. So, coming back so we essentially have four blood types type A type B type AB and type O. So, if you look at an RBC which is something like this biconcave disc. So, they have this surface antigens they have a for type A they have a surface antigen A what are antigens. So, this is something which I have been discussed I remember correctly. So, antigens are the molecule in whose response antibodies are produced. So, body has its own antigen and if body has its own antigens. So, technically body should produce antibody against it, but if it is of your own body they do not produce antigen antibody against those antigens. Those are the surface antigens which are present in the in our cell on the top of our cell, but there are diseases which are autoimmune. Body produces antibody against its own member it tries to it could not identify that this is your own some autoimmune disease like mysthamina gravus likewise you know there are whole range of autoimmune disease which are involved. So, these surface antigens are identified by that individual that is its own antigen that is its identification hallmark and similarly if you have a type B cell type B RBC. So, this is the RBC. So, on top of that they have another set of antigens which are called antigen B just for your understanding. So, these are the antigens I am putting them in red these I am putting in green. So, if you have type A and what you produce is that you produce antibody in your plasma I have already discussed about plasma. So, let me just rub this off just put the surface antigen here. So, these are the antigen. So, against this surface antigen body has antibodies which are called anti B antibodies A B stands for antibodies. So, they are something like this similarly for people having blood group B have anti B. So, if a person who is having blood group A donates a blood to a person having blood group B what will happen as soon as they donate the blood the anti A antibodies will come and will start hit upon the RBC's which are coming from blood group A. So, let me draw it for your understanding. So, for example, here is a person having blood group A if this person is blood group A. So, this person he has a anti B antibody in its plasma and this person's plasma they have anti B. Now, this person is donating to a person who has B blood group. So, in this person's plasma he has he or she has anti A antibody it is already present there nature has designed us some reason or other like that. Now, this is present in the plasma as soon as this A comes into the game. So, this A blood is coming RBC's of A these are A A and immediately the. So, and these are imagine these are the surface antigen for A and the antibodies against that which are I am putting them in red anti A they will come and bind here. And what they will do essentially they will rip this cell apart and they will kill this cell whatsoever blood which is being transferred or transfused to the other person will have no use blood will be all destroyed. So, this is what happens when it does not match then comes a blood group called AB this is the third one. So, I talked about A and I will talk about group AB. So, AB is a person whose blood cells have both I showed you in the green the anti B antibody anti B thing and you have that both or distributed all over the place randomly. So, that is why a person having AB could accept blood from both A as well as B because this person is equipped with they do not have any they have neither anti A or nor anti B. They do not have any of these neither they have anti A nor they have anti B. So, these persons are universal acceptor they can accept blood from anybody of course, I have an introduce the R H factor I will introduce it very soon as soon as I finish this then comes a group called blood group O blood group O is somebody like marginal cell like this which does not have any surface antigen. They do not have any surface antigen yet they have anti A and anti B antibodies in their blood in their plasma. So, let me just for your better understanding let me draw it in such a way that you understand all the groups clearly B, C, D here is single red blood cells I am showing and here you have these green colors are showing your surface antigen surface antigen A. So, this is blood group A this is B this is AB this is O surface antigen A and within the plasma you have anti B antibody. Now, blood group B they have this. So, they have surface antigen B surface antigen B and they have anti B antibody. Now, you have the third group of persons who have both the surface antigen presence they do not have some just they have neither anti A nor anti B and now you have the O they have. So, they have surface antigen both the surface antigen surface and for A as well as B this is the A and this is the B. So, and these persons have neither anti A nor anti B antibody yet they have anti A and sorry anti gen sorry I am sorry anti gen anti B antibodies. So, these are that is why blood group with O is called universal acceptor sorry blood group O is called universal donor they could donate blood to anybody and they can only accept blood from somebody who is having O and you have this AB which is universal acceptor they can accept blood from anybody. So, this is the first set of factor and mind it here for those might wonder is this the only thing there are at least 50 60 50 to 60 odd identification marker on the surface of red blood cells. But it is only 2 or 3 or maybe 4 which are of extreme significance, but that does not rule out what will happen with other factors be aware these in the population are most significant one as of now there is lot of research going on we do not get these cases at times these are rare happenings, but other say for example, if total we assume there are 50 such identification marker for 50 such identification marker in the surface antigen on top of it we are only talking about 2 surface antigens A and B their presence absent, but that does not mean there cannot be tomorrow F G H I J K likewise there are at least known 50 this is known this is the last time I was reading through it was 50, but that number may be increasing day by day with the explosion of genomics and proteomics at is exploding big time it is just statistically that concentration of the titre is low, but you never know maybe tomorrow maybe 20 years on the line we may discover other factors and the blood transmission have become much more complex as what it is today. So, we talked about 2 surface antigen A and B and we have not talked about the chemical nature of this and that we are going to talk just soon after this there is a third surface antigen factor I will be talking about that is called R H it is also sometime called D factor R H factor is again it is a protein on the surface. So, while I was drawing you say something like this if this is the R B C. So, we talked about these you know these surface antigens likewise and I told you there are other surface antigens which we are not aware of I am just putting them in different colors you know. So, that you kind of appreciate it like you know or likewise you know there is. So, only the major ones which we are dealing with is this one and this one which is for A and B there is one factor which is called D or which is also called R H it is called R H because it has been discovered in one of the monkeys in Africa called rations monkeys R R H is rations monkeys. So, this was discovered in the rations monkeys that why it is called R H and it is a protein on the surface. So, it is something like this something like protein sitting there if this protein is present we call it positive and if this protein is absent we call it negative based on that we have R H positive and R H negative. So, on top of what I have taught you as of now A positive A negative B positive B negative O positive O negative and then you have A B they have both they could have positive or negative. So, these are the broad classification as of now, but tomorrow you may hear some other factors which add up to this we may have a different kind of nominal actually there are because if you go through the research research papers in different where people write like in analyze bloods you will see there are so many other when those classifications are way too complex, but I am not getting the complex it, but I am giving a feel of the complexity it is just like think of a crowded street and there you have to identify a house it has it is all bar coded at this blood is belongs to this individual and it is so very unique. So, it is just in the population as of now and those antigens surface antigens are present in such a low concentration such a you are talking about a femtomolar you know picomolar it is really tough to identify them. So, we always identify the one which are in a larger concentration those which are smaller, but tomorrow when mankind will have much sharper tools much better tools to identify all these things I am pretty confident that we will come to know many other factors which ensures and may be blood transfusion will take quantum jump out there with identification of these different surface antigens on the surface of RBCs. So, after introducing this you know this R H factor everything now I will come back what happens how that influences. So, before I do so let me just take a detour and tell you that what are the. So, as of now I have not talked about the chemical nature of this. Now, what I will do I will talk about the chemical nature of these molecules and then I will move on to the pregnancy and related issues with it. So, the chemical nature of these if you remember I talked to you about the sphingolipids in while I was talking to about the lipids and I talked to you about the sphingolipids. So, what I will do now I will draw a sphingolipid just to rehash if you have forgotten and from there I will draw the story sphingolipids. So, sphingolipids essentially looks like something like this. So, it has a sphingocene moiety just you have to go through my previous lectures on the OH group out here this is attached to C H and H and from here there is a huge chain of fatty acid going through and out here this is the third moiety which is C H 2 O here is the X group this is important. So, here this part what you see is this part is called sphingocene go same part and this is basically a sphingolipids and this is the your fatty acid component sorry I just do it slightly wrong. So, this is included in so this is the fatty acid component and this X is the critical one. So, these sphingolipids if I have to draw the membrane again. So, if this is the membrane there are sphingolipids which are present like this out here along embedded within the lipid bilayers with other lipids. So, these sphingolipids what I draw has a wide range of modifications these sphingolipids at cell surfaces are site of biological recognition. So, sphingolipids for biological recognition. So, how they do so I have highlighted that X part to you now I will show you. So, what I will I will not draw. So, what I will do I will keep the fatty acid the I will keep the sphingocene moiety intact I will keep the fatty acid and I showed you that X now you see the variation in the X determines whether somebody has A somebody has B or somebody has AB. Now, let us draw it. So, here you have the sphingocene moiety. So, sphingocene moiety you here you have the fatty acid now start the game. So, now this is the case of antigen O you have a glucose GLC is the glucose then you have a galactose another fatty acid then you have galactose N acetylneurominic acid then you have another galactose sitting here and then you have a fucose which is another carbohydrate. So, this is the structure of O antigen which has both A and B. So, if you know O then so, what I ensure that always try to recollect the structure of O if you know O then you can divulge and say this is A and this is B because O contains both of them. Now, let us draw what is the A and B. So, O antigen we have dropped. So, this is this is what is essentially present on the surface of red blood cell this is structure. Now, for O there is one modification. So, everything remains sorry for A there is one modification everything remains the same nothing changes except there is one addition here which to draw that. So, again here is your sphingocene moiety fine here you have the fatty acid here you have the sphingocene. Now, you have this I draw you this GLC they have galactose glucose galactose gal N ac then you have galactose and then you have the Foucault's and here is that addition for A. So, now you are talking about A here is that addition it have you have another gal N ac this one small galactose in neuraminic acid changes the fate. So, that determines that you have A E blood group A antigen A surface antigen then what is B now let us draw the B. So, again you have this sphingocene moiety you have the fatty acid A l out here and then starts here. So, you have glucose galactose gal N ac then you have after gal N ac you have galactose and then you have the Foucault's and. So, here in the in the case of A you got a gal Nac and in the case of B you have just a galactose present here. So, this is the one which determines that you have B in one case you have galactose in acetyl neuraminic acid one case you have just a galactose residue this chemical signature it has been very nicely highlighted those of you are interested for extra reading we should go through leninger in the leninger fatty acid section it has been highlighted very nicely very beautifully shown in picture and that will help you to understand this is structure much better. But that is what is where essential for you to understand that these blood groupings are molecular recognition tools of biology and they are determined by different kind of lipids glycol lipids glycol proteins. So, R H factors similarly is the protein which is just like what you see here a glycol I should say glycol lipid because you have a lipid group on which you have this carbohydrate moieties which are attached like galactose glucose gal Nac glucose likewise in the case of R H factor it is a protein. So, you have this lipid polar groups on which there are proteins which are tagged which are essentially lipoprotein protein adhere to a lipid. So, these proteins act as those barcodes which makes you positive or negative from here I will come on to what happens in a pregnancy situation. So, for that you have to understand when a women is pregnant a baby is growing in the womb. So, essentially the blood circulation is slightly separated from the baby and the mother this droid that will make more sense to you. So, what happens? So, now we will be dealing with R H factor and pregnancy R H factor and so think of a mother was. So, let us draw the two blood vessels here in the mother's womb the baby is growing and a mother is R H irrespective of R H negative. So, this is maternal tissue and now let me draw the fetal tissue which I will put in green just for your understanding. This is like this and imagine the fetus is R H positive it has a positive R H factor and here we are in the fetal tissue and this women is going through her first pregnancy this is not a second pregnancy this is her first pregnancy. So, women this women does not have any antibodies as of now because it is R H negative does not have any antibodies against R H factors because it has never been exposed to R H positive situation. So, the essentially what this boils down the blood which are present in the mother's side do not have any such marker. Whereas, in the case of fetus side the baby whom she is going to give birth has these R H proteins R H antigen on surface of the protein on the surface of these R B C's fine. So, these are R H surface antigen. So, during the first pregnancy during her first pregnancy during the childbirth zone comes. So, again I have to show you through the drawing that will make more sense. So, during the delivery basically this is what happens cutting the umbilical cord and there is a bit of a blood exchange which takes place. So, what essentially happens are. So, this is the fetal side and this is the maternal side maternal tissue and these are the fetal R B C's with the with these factors with this R H surface antigens on them whereas, these are the mother without any R H antigen R H surface antigen. So, some of these R H positive cells gets into the mother's circulation and as soon as it gets into the mother's circulation because of the presence of these what you see this blue color and surface antigens which mother is never exposed to it starts producing antibodies against it. It produces a series of antibodies it is just like as if mother is getting vaccinated it is a almost equivalent to that the mother is getting vaccinated because it is low tighter of it is going. Now, for the first pregnancy it will be fine the child will have no problem child will survive, but if this mother goes for a second pregnancy what will happen already the mother has and imagine the second pregnancy the again the fetuses R H positive. So, let us draw it that will make more sense. So, already mother has produced antibodies against it. So, now the mothers follow the same color code. So, mother has now these are mother cells and on top of that they have and they have antibodies against the R H positive these are the antibodies against R H antigen. Now, if again the fetus becomes R H positive as soon as the R H positive. So, the mothers from the mother blood the R H antibodies will come and will start breaking down the cells of the fetus blood blood cells of the fetus. And essentially what will happen either the child will have a premature death inside mother's womb or the child will be very will be produced very anemic. So, these are the situations for which doctor has to take a special care very very special care. So, that these are the reasons why the understanding of the blood grouping and all the surface antigen on top of the blood on the on the red blood cells is. So, so very essential because these are the signatures which makes all the difference whether it is a pregnancy or whether it is a blood transfusion or any other situation. So, just to rehash. So, this mother was R H negative fetus was R H positive and there is a blood exchange during the blood exchange mother started producing antibodies against R H factor R H surface antigen. And because of that antibody production what happens essentially yeah the first child will have some bit of a first child may be born bit of a jaundice which I am going to come now. But the second child survival will be in a big question because mother will have a very high titre of R H antibodies because mother is herself is negative for R H. So, that is where lies the whole classification A positive is A R H positive A R H negative B R H positive B R H negative likewise O R H positive O R H negative probably one of those very rarest of the rarest individuals for whom you really needed another O negative. So, now I will move on to the jaundice which is the tail piece of this whole circle which we covered just like a blood circulation it is will be just coming back to the point where we started with R B C. So, that was the so reason why I that reason for not introducing jaundice at that time because now you will be able to appreciate jaundice much better in the light of red blood cell white blood cells bloodlets blood grouping R H factors will be able to appreciate jaundice far now let us get back. So, I will just draw a very overall flow chart to explain what exactly happens in jaundice. So, if you remember while I was talking about I was talking about how R B C is getting. So, let us start basics R B C has a life span of say 120 days fine so now after 120 days or the R B C have to be destroyed and that is done by in the by the macrophages. So, I will pick up the story from there production of R B C is after what happens after 120 days how it is getting broken down and what happens to those broken down product how they are being regulated. So, coming back to the slides so this is we are into the bone marrow now within the bone marrow the R B C R B C formation this is the bone marrow and here you have the R B C formation. These R B C's once they are formed they are in circulation and then after their 120 days life span they are being engulfed by the macrophages this is one reaction which I have shown you inside the once this R B C's. So, these are the R B C's inside the macrophages what happens they are being chopped off into pieces and it generates iron P 2 plus and you have the amino acids and you have these amino acids are brought back to the bones iron using transferent iron bind protein is brought back to the bones. Now, you have the hemoetine which is converted into bilverdine and bilverdine is converted into something called bilirubin and this bilirubin from these macrophages moves to the liver which we are discussing in the digestive system. In the liver this bilirubin through the duct of the liver is sent for excretion. So, there are two roots from here either this goes to the kidney where basically bilirubin is directly put into the urine there is one root there is another root this bilirubin reaches the large intestine in the large intestine bilirubin is converted into a molecule called uro bilirubin in gens uro bilino gens and stericobilino gens. These molecules further converted into uro bilins and stericobilins and part of this uro bilino gens are excreted via urine and these uro bilins and stericobilins are eliminated in the feces and that is why you will see the color of the feces is yellow white is yellow it is yellow because of these different compounds which are present there whose disignature is yellow. So, now imagine what will happen if the duct from where the bilirubin is being thrown out from the liver is blocked or liver has problem that is exactly the situation what happens in chandis when the liver ducts through which. So, coming back to the flow chart what I was drawing for you guys. So, there are ducts through which. So, here in the liver these duct kind of gets blocked because of the malfunctioning and this leads to a straight call chandis and this could happen by multiple roots there are multiple roots for this to happen this could happen because of some pathology here some you know microbial attack some viral attack which leads to the damage in the liver. So, that the ducts which are supposed to vent out the bilirubin fails to do. So, and what you see on your skins and everything it becomes yellowish because your bilirubin concentration in the blood goes up and that could be detected not from the blood sample not only from the blood sample it could be detected from your urine and it will see the there is enormous amount of yellowish the you see your skin colors like in along the nails and everything you see yellowish because it is the this bilirubin bilirubin concentration goes up and this is how it all happens it is from that he molecule which convert into bilirubin from bilirubin to bilirubin from that then the bilirubin has to be sent partly to the kidney and partly to the large intestine where stereo bilinear gens stereo bilinear gens stereo bilins euro bilins likewise this is a whole complex set of reactions which takes place and when it fails to do. So, this is what you see the case of John this. So, just to you know summarize what all we have covered we started with RBC so we covered almost 5 lectures on this we started with RBCs we talked about it oxygen carrying capacity using hemoglobin there I requested you people to look for the structure of the hemoglobin then from there we moved on to the blood clotting we talked about the platelets and how from the mega karyocytes these things are formed after that we talked about the WBCs and the WBCs we talked about how they are formed and in between of course we talked about the formation of all the different blood cells and then we talked about the WBCs and we talked little bit very little bit about the immunity in at immunity and acuity immunity by the in at immunity we talked about all the different organs of our body which prevents using different kind of toll like receptors does not allow the entry of the pathogen or occlude the entry of the pathogen then we talked about the acuity immunity in the form of T and B cells and in the form of different antibodies which are produced by the body and lastly we where we started with RBCs we end up with RBCs we talked about the identification signature of the major component of the blood which is RBCs how they are being identified in terms of the surface antigen A, B, A, B and O and then we talked about the RH factor now how RH factor affects the pregnancy of women and lastly we exactly ended where we started in the first class talking about jaundice what jaundice is all about thanks a lot.