Antibodies | Immunoglobulins | IgG| IgM | IgA | IgD | IgE | Immunology

today we will be talking about antibodies immunoglobulins write the concepts about immunoglobulins are very important these are one of the most important molecules in our body you cannot survive without them in such a hostile world where there are so many microbes and so many pathogens which are trying to invade our body and Destroy destroy our tissue now exactly what our antibodies bodies they are also called immuno yes please you know Global lens now what are exactly antibodies from where they come in our body and exactly where they are present right major portion of the antibodies circulating in the blood right antibodies are special protein molecules antibodies are very special type of protein molecules which are secreted by plus muscles antibodies are special type of protein molecules which are secreted by the plasma cells now what what is a plasma cell actually whenever a b lymphocyte whenever a b lymphocytes becomes fully differentiated and becomes fully functional right it starts producing antibodies it starts secreting y-shaped molecules or antibodies so antibodies are the products of proteinaceous product of well differentiated B cells or protein products of plasma cells is that right now exactly in the blood in which component of the blood antibodies are present yes please question goes to very impressive doctor Dr Safa in which component of the blood antibodies are present let's come with very simple thing everyone knows that blood has two components cell then yes please plasma and plasma has many components is that right one of the component is plasma proteins actually antibodies are the part of the plasma proteins this is a very basic concept that where antibodies are antibodies are present yes present in your blood as the proteinaceous component of the plasma the plasma has many type of proteins now we have to see that within the plasma and within the plasma protein where antibodies are exactly present so Dr Israel May answer us that your plasma has proteins and one component of the plasma proteins are basically antibodies now which component of the plasma protein is having antibodies I'm about to be impressed by him I think he is very serious right now he doesn't want to answer so I will do it myself look one of the way let's suppose that on this filter paper we put a drop of plasma right we put all the plasma proteins here we put all the plasma proteins here you know plasma protein the positively child are negatively child light keeps secrets you don't tell me plasma proteins are negatively charged is that right at body pH which is 7.4 by the way at the body pH plasma proteins are negatively charged now because most of the plasma proteins are negatively charged if you put a drop of Plasma on this filter paper and you run the current across it for example you put negative electrode here and positive electrode here of course plasma proteins will move from negative electrode towards positive electrode because plasma proteins are themselves negative so they will be repelled by the negative and of course they will be attracted to the positive so plasma protein will start moving now as plasma proteins start moving this segregate into group because all the plasma proteins do not move right with the same speed on this paper you can answer this if plasma protein is very heavy right that will move fastly or slowly slowly actually those plasma proteins which are more negative and smaller in molecular weight there will be more smart and they will Rush fastly so what really happens that some of the plasma proteins will reach here right then there will be some here here and here and here now these are the plasma proteins which are smallest in molecular weight right and they're more mobile right so they will come over here this was the movement right heavier plasma proteins will be left behind is that right if you divide the plasma protein you know segregate the plasma protein by this way this is called process of electrophoresis have you heard of it process of Electro for Aces when you do electrophoresis of the plasma proteins right this Electro for races is that right now electrophoresis when you do the plasma proteins the smallest molecule weight will be here and as the plasma proteins become more and more heavier they are segregated in a different band right actually these plasma proteins as a group are called yes please albumins because albumins are the smallest molecular weight and this whole group of plasma proteins this three this is called Global lens Global length and this is post fibrinogen is that right another way to show this is that you draw a graph graph is that if you put molecular weight here and you are classifying the plasma protein according to the increasing molecular weight on this side and plasma protein concentration on this side then this is albumin what is this this is albumin and these are Global length am I clear now out of this this is Alpha globulin these are beta globulins these are gamma globulin it means primarily plasma proteins are alumin and globulins and globulins can be separated Global in the globular protein can be separated right according to the molecular weight into Alpha globulins beta globulins and gamma globulins is that right am I clear albumin's molecular weight is about approximately 70 kilo Dalton but globulins molecular weight is from 90 to 120 kilo Delton hello Del turn right now within this shade where exactly antibodies are present that is the question now I think you should be intelligent enough to guess in this band this is a woman Alpha globulin beta globulin gamma globulin and exactly where the plasma proteins are segregated the soil Dr Safa of course they are not Alpha and beta they are in gamma actually if you study if you study these plasma proteins these are antibodies if you study this band this is antibody so where are the plasma protein in your body plasma proteins are of course in the plasma but within the plasma protein where are the antibodies antibodies are part of the gamma globulins actually that is why antibodies are also given another name what is that name gamma globulins simple as that am I clear so there are three names the antibodies they are immunoglobulins these are gamma Global lens now these are three same name for the same type of molecule is that right that gamma globulins mean those globular proteins which are part of the gamma fragment right or gamma band on electrophoresis of plasma protein immunoglobulins mean what those globulin proteins which have immune function they are also antibodies and what are antibodies antibodies are those protein molecules which are secreted by well differentiated B cells called plasma cells and antibodies specifically this is very important antibody molecules specifically react with antibody molecules specifically react with the antigens which stimulated the formation of those antibodies so what are antibodies antibodies are protein molecules secreted by the secreted by the plasma cells which which react specifically with those antigens which elicited their or stimulated their formation or stimulated their synthesis no problem up to this now if I give you a statement I say that antibodies are those globular proteins right which are produced by the plasma cells and they react with specifically with the antigens which lead which stimulated their formation plus I can say antibodies are also called immunoglobulins because why we call the antibodies immunoglobulins because antibody molecules are just proteins which are part of the globular globulin components of the plasma protein and which component of the globulins gamma globulins is that right so next time if I someone asked you that in your blood where the antibodies are present you say remove the cells left is a plasma Auto plasma separate the proteins run the proteins electrophoretically and find the gamma band and all your antibodies will be present in gamma band am I clear there's no problem up to this now we come to really basic structure of antibody as I told you these are basically proteins with little carbohydrate component and when protein they were little carbohydrate component we call them glycoproteins and proteins have a little carbohydrate component what we call them glycoproteins to be more specific antibodies are glycoproteins antibodies are glycoproteins now let's come to the basic structure of a typical antibody antibodies basically a tetrapeptide any antibody is basically a number one condition is it is a tetra peptide when I say that antibodies are tetrapeptide it means how many peptide chains it has four it is tetropeptide consisting of two heavy chains and two light chains a typical antibody molecule is a tetrapeptide with two heavy chains and two life chains held together by yes held together by disulfide Bond Die sulfide bonds so again what is antibody antibodies are tetrapeptide antibodies of force glycoprotein molecule right it is a tetrapeptide consisting of two heavy chains and two light peptide chains all of them are held together by disulfide Bond Amic layer and it is usually a y-shaped molecule let me make your typical antibody molecule antibody molecule should have four peptides okay I will make two heavy peptides here why we call this peptide heavy peptide or heavy chain right this is a heavy chain and there must be another there must be yes please another heavy chain so antibody has two heavy chains with that it has to yes light chains it has to light chains and there are two heavy chains and there are two light chains and they are held together by yes please disulfide bonds these are the disulfide bonds which are holding them together and of course they should be held together by disulfide bonds now let's go back to the definition antibody is of course an immunoglobulance which is secreted by plasma protein present in the plasma gamma globulin component right antibodies are basically tetrapeptide the four peptides having two heavy chains and two these are two heavy chains and two light chains held together by disulfide bars am I clear this is a typical uh you can say shape of the antibody now antibodies the specific function of the antibodies they should bind with the antigen in a specific manner right now in which part of the antibody antigen binds yes you will tell me you could just come here and put your finger in which part of the molecule antigen will bind exactly yes just tell it hurry up I don't know top means how many points are there where antigen can bind you don't know the just come come come here you know be brave yes okay no no I'll give you here this is antigen right very sad because it's going to bind to the end you draw it there exactly where it will buy it okay is it right over there and you are near the point but honestly you should be laughing here you know why because from here it can escape away no no no no no no it should be in between them like here and then it will you know both chains will cooperate to catch it you see antigens are not here there they will run away is that right actually a part of a light chain and part of a heavy chain together grab the antigen this is very important to know this is one antibody molecule having two heavy chains two light chains right and one antibody molecule which I'm showing here can bind with two antigens or two epitopes of Cyanogen is that right now let me tell you actually the antigens which are direct sorry the antibodies 12 which are directed against different antigens must be different in this area let me tell you what I'm telling for example here is one antigen like this and other antigenous like this another antigen is do you think these antigens the same or different from each other they are different from each other and antibodies will bind with do you think one anti antibody can bind with all three of them no antibodies are very specific the antibody which will bind with this hydrogen will not bind with the other ones is that right every antibody is very very specific for a given antigen a closely structural given anti-gen now if I say that antibody body which is going to react with this it cannot react with this an antibody which react with this antigen cannot react with the other two it means this part of the molecule you know this part of the antibody molecule should be diff different in different antibodies for different antigens are you understanding for example let me tell you that I will make a simple diagram that let's suppose this is like now they can catch this antigen is that right in the same way now it will more specifically fed suppose this is integer number one this is antigen number two this is antigen number three is that right am I clear now opposite to that if there's another antibody and which will fit in which antibodies directed for that that antibody will have some difference now uh do you think antigen number one can bind here no it is designed for integer number two antigen number two can better fit over here is that right so what we see that this part of the heavy chain and the light chain is very varying from antibody to antibody when antibodies are directed awareness for different antigens so we say that let's suppose if we have three antibody molecules one is for this antigen other antibody molecule is for this antigen and other antibody molecules for this antigen then what will happen all those antibody molecules which are directed against different antigens should have this area with different configuration it means this area varies according to the specificity for antigen reaction that is why this part of the light chain this is the light chain this part of the light chain is variable light chain and this part of the heavy chain also vary so this is variable heavy chain this component this part of of course this is a peptide chain so it should have here A minor end and here it should have carboxyl and the same with heavy chain should have one Amino end another Js carboxyl and you understand this then every peptide chain has on one side a minor and another carboxylide so what really happens that minor end of the light chain and a minor end of the heavy chain they are having a domain domain mean and a region of amino acids sequence within a peptide chain this domain is variable so this is variable domain of the light chain this is variable domain of the heavy chain is that right but this this component this component this will not vary it is constant it is constant we call it constant of the light chain and constant of the yes please heavy chain this is variable of the heavy chain and this is constant of the heavy chain and if you come to the light chains this will be what variable of the light chain and this will be constant of the light chain is that right no problem up to this let me make it more clear let's Suppose there is star antigen there is spherical antigen and there is potato ending the star antigen ball ball antigen b a double ball antigen and potato antigen now antibodies reacting against them will be same or different antibodies let's suppose I show the anti-body for this these are the heavy chains all of them I'm showing in a very simple way you can understand now these are three antibody molecules but antibody molecule which will react with the star let me show star here is going to react with the star this part of the light chain will be variable and this part of the heavy chain will be variable of course here if on one side it is binding with the star on the other side will it will also bind with the star so the same variable which is here on the heavy chain here also same variable will be there and variable will be there on the light chain author now if this molecule is going to be this ball antigen then what will happen now here is the let's go they put the ball do you think the variable regions can be same as star no so they will vary from in this area you understand it now we come to this for that antigen Suppose there is another antibody we specifically react with that of course it will have two heavy chains and just place two light chains right now this antigen is like this now you understand it that basically a particular antibody will react only with the specific antigen every antibody does not react with every antigen and why a specific antibody molecule react only with the specific antigen because antigen binding area antigen binding area of the antibody has variable regions and these variable regions write vary from one group of antibodies to the next group of antibodies to the next group of the antibodies as antibody group change their specificity for the antigens right now come back so this was variable domain domain of the light chain and this is the constant domain of the light chain then this is a variable domain of the heavy chain this is the constant domain of the heavy chain heavy chain has many constant domain uh constant domain number one constant domain number two constant domain number three right one constant domain number one constant domain number of the heavy chain number two or three and later on we'll find that most of the antibody classes how many antibody classes are there there are five basic classes of the antibodies right ah the five classes of antibodies are called can you tell me immunoglobulin G a immunoglobulin a molec a class Amino globulin M group class immunoglobulin e and immunoglobulin D we call it gamed and all the amino globulins can be primarily divided into five classes I will tell you later how we divide them on what what base minoglobulins can be divided into five classes but antibodies can be divided into five classes this is global M with immunoglobulin IG now you understand why we call it immunoglobulin these are the globular proteins from the globulin component of the plasma proteins having immune function and belonging to the class of G or class of a right or class of m e or D out of this m e me very important you know me has longer heavy chain foreign M and immunoglobulin E has heavy chains with constant number one constant number two constant number three constant number four right so constant of the heavy chains in a munoglobulin Class M and Class E is how many 1 2 3 and 4 but their heavy chains are having only how many constant domain constant domain number one two and three but IGM and IGG have how many one four one additional that is four is that right now let's review it antibody molecule has how many peptides a typical antibody molecule is how many peptides four two are heavy chains and two are light chains while light change are called light chain because the molecular weight is less usually light chains molecular weight is about 25 thousand and molecular weight of the heavy chain is 50 000 to 70 000 depending upon there are three constant of four constant region right so the four peptide held together by the disulfide bond two light chains two heavy chains in a typical antibody molecule is that right now on the amino ends of the heavy chain and a minor end of the light chain there are which areas variable areas this variable area of the light chain this variability of the heavy chains in between these two variable area what is fitting there antigen fats is that right so antibody binds with the antigen through the heavy chain as well as through the light change through is variable domains and then there are there's only one constant domain of the light chains but heavy chains have how many three or four constant domains any question after this there's no question no problem up to this now another thing that some doctors they were doing some experiment with the antibody molecules and what did they do let me tell you suppose I draw here a typical antibody molecule I hope you understand it isn't it and what did they do that put these molecules in a flask right put the antibody molecules in flask but in the flask in this container after putting the antibody molecules I think I'll make the light change color different so that you can appreciate the diagram better these are the antibody molecules which we have put into this container and of course they are held together by yes please disulfide bonds now what this researchers did they added a very naughty type of enzyme what is this enzyme this is called papain they added a papine to this and they were surprised that the pain code break down this molecule at a special points okay I'll keep my color scheme same right uh they found that type in could cut this molecule at this point digested the molecule of antibody antibodies of protein that were digested by this Pepin and papine is a enzyme which attacked the this region this is called hinge region what is this h i n g hinge region attack the hinge region and digest it from this point and this point now antibody break down into how many components how many fragments yes question goes to Mr yes how many antibodies broken to how many components the three components look at it one component is this another component is this and another fragment is this so antibody break down into three fragments so what did they do they put antibody molecules in two container and add the paper into that and pepaint digested every antibody molecule into how many fragments three fragments and these fragments which were made out of them this fragment has write a minor end of the heavy chain and and complete light chain right held together another minor end of the heavy chain with complete light chain and this portion has remaining heavy chains held together by disulfide bond is that right now then after that they added the antigen to this what did they added let's suppose this is the antigen for that particular antibody they added the antigen to the solution and they came to know that these fragments antigen bind with these fragments right producing antigen will bind at this point or will the antigen bind here now will antigen bind here here will antigen bind here will it bind here but it will bind here so in this way uh the researcher found that when antibodies are put into a container and treated by the papine antibodies will break down into fragments some of the fragments will be binding with the antigen and other fragments well not bind with the antigen these fragments which do not bind with the antigen they found they will go to the bottom I mean bottom of the flask these molecules will these fragments will go to the bottom of the flask and there they will crystallize they will change into crystals due to that reason doctor said when an antibody is treated by the papine when an antibody molecule is again let's draw it here and here this is disulfide disulfide Bond here is your light change isn't it so they found when they treat with the pain antibody will break down at this point is that right we divide into three fragments out of these three fragments two fragments were able to bind with the antigens and other fragment was unable to bind with the antigen and this fragment went down and it crystallized so they called this fragment of the antibody fragment which crystallizes FC portion of the antibody in the Box you very frequently read FC portion of the antibody or FC fragment of the antibody c c originally was put for the crystallization that this component of the antibody will crystallize once antibodies are treated with the papain and this fragment this will binding with the the fragment which was antigen binding we call it fragment antigen binding so we call it Fab so basically a classical molecule of antibody consists of four peptide having two heavy chains two light chains held together by disulfide bonds and having two Fab fragment and one FC fragment right or portion Amer now actually this FC stands for crystallization but it also should remind you that with this end there is what carboxylent of the heavy chains because a minor end was here for the heavy change so C for crystalline C for carboxyl and C4 complement activation some of the antibodies activate the complement this is the portion of the antibody which activate the complement this is the portion of the antibody which activate the complement it means in this domain more specifically if you remember there was for heavy chain how many domains were there heavy chain variable constant heavy chain one constant heavy chain constant heavy chain two and constant heavy chain three or some cases four uh actually this is the constant heavy chain two which are the capability to activate the complements so complement activating part of the antibody is part of the FC fragment so FC fragment should remind you that some of that this portion crystallizes this portion is having carboxyl end of the heavy chain and if if this antibody is going to activate the complement then FC portion will activate the complement and you will know later that IGG class of the antibody crosses placenta IGG class of the antibody from the mother through the placenta goes to the fetus so actually with the placental cell this portion of the antibody bind and help the antibody to cross through the placenta so it should remember remind you also about Crossing cross through yes play center and you know antibodies bind with specific type of cells for example later on later on you will learn ige specially bind with the catches the mast cell is that right so again IGG will IGG class of antibodies will catch the Mast cello bind the mass cell with this portion so catching cells am I clear no problem so FC portion stand for what originally stranded for this fragment could crystallize but this should also remind FC strand for carboxyl and FC stand for fragment which activate complements fragment which helps the antibody to cross the placenta and fragment of the antibody which helps it to bind with the cells any question up to this an Fab portion it's enough to say that this is a fragment which is antigen binding fragment no problem up to this okay then so we can say that antibody one antibody has what thing antibody plus Pepin just goes to what thing antibody will go into what antibody treated by pain will go into two Fab fragment plus one FC fragment is that right now we do another treatment take an antibody molecule okay let's make some seductive color scheme those are right this is a typical antibody molecule of course consisting of two heavy chains and two light chains is that right now rather than pain this time we treat it by pepsin you have heard of pepsin foreign it is also proteolytic enzyme not a name of a girl pepsen right uh when antibodies treated by the pepsin ah what at which point pepsin will digest the antibody it produces multiple digestions at this point so actually now when antibody is treated by the pepsin then FC portion is digested at multiple fragments but both Fab portion are still kept together the important point is that pepsin attack the antibody molecule ah not at the hinge region rather distal to away from the hinge region towards the carboxyl end of the heavy chains is that right due to this reason uh both Fab portion are kept together am I right now you will help me rapidly if I say this is one antibody molecule and this is another antibody molecule let me take your test enzyme attack here and divide the antibody molecule into how many fragments three which enzyme is this yes papine and if I say that enzyme attacks here and both Fab portion are still held together what is this no problem up to this for sure okay so now we have learned something about basic structure of the anti-body another thing then when antibody is reacting with the antigen when antigen and antibody bind together they are held together by what type of forces and what type of bond you know when they come together they make a bond isn't it so what type of bond is present between the antibody and antigen yeah I'm about to be impressed by you okay let me make our original molecule again I hope you remember what are these chains I'm drawing heavy changed and what are these chains yes light chains and rapidly tell me what are these bonds I'm making disulfide bonds that's good and what is this fragment variable of the heavy chain and this is also variable of the heavy chain and what should be here this area variable of the light chain and what should be here variable of the light chains then let's suppose I'm going to make the antigen if antigen is like this right now this antigen is going to fit here then what will happen what was this area constant or variable yes variable now when this will fit into this I think I have to make to make this a little lengthy so that it should look more proportionate with the yes now this is caught over here and right so we say antigenous caught it's caught in between the variable region of heavy chain and variable region of the light chain this is what you already know now I know a little more actually within the variable region there are very special areas which make the fitting of which make the fitting of variable region more better with the antigen and these areas are given an additional name you know this is making a better threat isn't it these areas are called hyper variable regions what are these called these three are called hyper variable regions so we say within the variable region of the light chain and within the variable region of the heavy chain there are small amino acid groups right which are called hyper variable regions which make The Binding between the ah you can say antibody and antigen as precise as possible very very precise is that right now I will draw the same thing here and you will tell me what's going on here foreign yes now you will tell me that this is variable of the heavy chain and this is variable of the light chain and antibi antigenous caught over right now within the variable of the light chain what is this region hyper variable regions is that Claire one thing which is very important to know that in a given antibody molecule the antigen which bind on the same side one side that is the same antigen is going to bind on the other side as well right so both sides have the same antigen specificity am I clear no problem up to this right then I was talking about with which forces they are held together or which type of bonds are in between them what type of bonds are in between them the forces are the forces with which antibody and antigen are interacting those forces are very simple forces these forces are yes have you heard of electrostatic forces Electro static forces let me tell you how they are coming for example a minor asset which is present over here is positively charged and minus acid here is negatively charged the attracted is attracted to each other you say they are held together by electrostatic forces or by the wonder wall forces you know wonder wall forces wonder wall forces so there are electrostatic forces or the wonder wall forces this wall is not that wall on which you sit and fall down right this is V so electrostatic forces and wonderful forces keep the antigen and antibodies together when they are specific for each other and what type of bonds are formed in between is this ionic bonds or are they covalent bonds right or they are like simple hydrogen bonds and hydrophobic bonds yes yeah Dr Safa is trying to tell you know the bonding between the antibody and antigen is one way to tell is that is it strong bonds or weak bonds okay only tell me this thing the weak bonds right if you bring you know let's suppose if there are you bring lot of antibodies right and some of the antigens May dissociate and go to the other antibody if all the antibodies have same antigen specificity so these are these bonds are not permanent bonds they are somewhat reversible Bond or they're weak bonds so we can say that these bonds are not ionic bonds these are not covalent bonds these are simply yes hydrogen bonds and hydrophobic bonds so the forces which are keeping the end specific antigen antibody molecule together are wonderful forces and electrostatic forces and making very weak bonds like hydrogen bonds and hydrophobic bonds am I clear to all of you is there any special question here there is no okay let's have a break now some more basic concept about a typical antibody molecule right so we were talking about that antibody molecule that tetrapeptide now we have to develop a relationship between tetrapeptide we should be clear about these terms and and heavy chains light chains fragment Fab fragment C and then we should develop a concept what is monomer monomer molecule dimeric molecule Dynamic antibody molecules pentameric I will teach you this phantomeric molecules what is the concept of affinity and avidity right and what is the concept of valency you already know about the tetrapeptide we said that every antibody molecule is basically a tetrapeptide made of two heavy chains and two light chains right and a typical molecule has two Fab fragments if it is treated by papine and one FC fragment these terms I will explain now we go back to our typical molecule that that's why these were heavy chains and these are light chains all of them are held together by disulfide Bond now actually this whole tetrapeptide is considered one monomer this is considered one monomer and in simple diagrams it is shown like this actually these part of the Y are representing Fab fragment and this stem of the Y is representing FC fragment that is why very commonly you find antibody molecule like this right made in the box so basically when you see a antibody molecule like this it is fundamentally a tetrapeptide but when these four peptides are held together by disulfide Bond we say this antibody molecule is one monomer it is that right now sometimes it happen that more than one antibody molecules are held together they are held together this is one monomer right and this is spores another monomer and if these monomers are held together by another peptide chain this peptide chain is holding them together this peptide chain is joining them so we call it joining component of J component what we call it J component if more than one antibody monomers are held together by J chain or J component right or J chain joining chain we say now we are having multimeric molecule now we are having molecule and this multimetic molecule has two monomers so we call it this multimer is dimer just multimer is dimar sometimes would happen that with the joining component there are one [Music] um to three four and five now in this case this J component is holding how many chains together it's holding five chains together so we call it pentamer this is this type of you can say grouping of the antibody molecules right in which five monomers are together and held together by the J chain this is called pentamer so when we are talking about these terms when I say that there's a this antibodies monomeric it means this antibody exists in this form if I say there is another antibody which exists in dimeric form it means its exists in this form and if I say that a particular antibody group is pentameric it means it is existing in this form now we have to develop the concept of valency also valency mean that one group of antibodies can bind with how many antigens for example this can bind with how many antigens only with two so we say this monomeric molecule is having two valences so we say this monomeric molecule is divalent and this monomeric molecule is tetra valent and this monomeric molecule is yes it can bind how many antigens then so it should be decavalent you understand it so now you should know that when we are talking about antibody molecules these special terms are meaning exactly what concept when we say an antibody molecule is tetrapeptide it means a typical antibody molecule is too heavy chains and two light chains when I say that antibodies of different classes may exist as monomer or dimers or pentamers it means we are talking about that if I say that for example immunoglobulin IGG it exists in monomeric form it means there is no J chain holding multiple molecules together if I say that immunoglobulin a group on the in the body secretions are dimeric it means they are held together by jhn two monomer the hell together by or if I say that immunoglobulin class of IGM and the serum is in pentameric form it means it is holding how many five but if I say that let's suppose this is this molecule belongs to Amino globulin G Class so we say this is monomer with divalency and if it is IGA this is dimer with Tetra valency if it is IGM molecule in the blood or plasma or serum then it is pentameric molecule with deca valency valency am I clear any confusion up to this there's no confusion okay so this concept is clear that valency valency refer to the group of antibodies binding to how many groups of antigens is that right or one antibody can bind with two antigens it is divalent but if it is dimer it will have Tetra valency if it is pentamer it will have deca valency no problem now we have to come across another term concept of affinity and everyday concept of affinity and avidity let me tell you that what is the meaning of affinity between the antigen and antibody right affinity let's suppose this is one antibody molecule this is another antibody molecule now both of them okay first I will make the antigen here this is the antigen and here this is the antigen now this antibody molecule is having these variable what are these variable regions which are binding with antigen now we make another antibody molecule and this is what antigens these are rates which portion let's suppose this antibody molecule number one this is antibody molecule number two what do you think antibody molecule number one is holding the antigen more tightly our antibody molecule number two is holding the antigen more tightly two actually that these interactions between the very variable and Hyper variable region of antibodies and ah between the antigens these interactions they determine how tightly antibody will hold the antigen right this tightness or strength this the strength or the power with which one antigen binding site binds the antigen this strength is called Affinity so molecule number one will have less affinity for the antigen and molecule number two will have more affinity for the antigen is that right for example there's a beautiful girl here and her sister is holding her hand Affinity will be more or less as compared to her boyfriend a very new boyfriend holding her a hand where Affinity will be more new boyfriend not old one all right so so what I'm saying that affinity mean that if antigen antibody are interacting how tightly they are holding each other together or how what is the strength of the power with which one one antigen binding site is interacting with the antigen or as Shan is saying exactly what is The Binding Force what is The Binding force between the antibody molecule and antigen Emma clear this concept is called affinity but everyday is a slightly different concept affinity mean Affinity refer to The Binding force between antigen and antibody at one point everyday mean a different thing let me tell you let's suppose that there's a very big antigen it's a very big antigen with multiple points with which antibodies can yes it is okay I'll make it a simpler diagram so that you don't become afraid of this okay this is a very big antigen the small epitopes epitopes are the points exactly with which the antigen binds now look if a monomeric antigen come antibody come this will react here and here only at two points and if polymer or multimeric antibody come do you think monomer has only two point to bind but dimer has how many points to bind for and if pentamer is there how many points of binding especially in large antigens 10. so total Force with which the okay another I will repeat it again this is monomer this is dimer monomer is actually divalent and dimer is actually tetravalent right Affinity depend on when we talk about Affinity we are just talking about that one antigen point and one antibody Point interaction but when we talk about ability we are actually looking at all the affinities in a group together this binding Force plus this mining four plus this binding Force plus this binding Force Affinity at 1 Affinity at 2 Affinity at three and Affinity at four all affinities together are called avidity what are they called is that right so again I will repeat ability mean that at how many points antigen antibody are interacting as IGM molecules they are pentameric so their ability is more but IGG molecules are only monomer so they are having only divalent so their ability is less am I clear or not no problem up to this okay now we start develop some concept about the different classes of antibodies so antibodies have all of you know that basically antibodies having are having five main classes now according to which concept what is the reason to divide your antibodies into five classes primarily you have any idea why antibodies are primarily divided into five classes there must be a reason yeah no that is not the real reason why antibodies are for example look you bring from my blood again you from my blood you bring all the plasma protein out and run the plasma proteins on the electrophoretic strip and from the gamma band you bring all my antibodies out all the antibodies which you bring out of my gamma component of the plasma proteins they can be basically classified into five groups on what base they are classified yes yeah that's good that's good very good actually uh primarily five types of heavy chains can be produced and two types of the light chains can be produced the plasma cell can produce primarily how many types of heavy chain five types of heavy chains and two types of life change life change now if you let me make if you put all my antibodies out of my body as you bring all my antibodies out and classify them according to the heavy chains how many groups will be found five groups let's suppose this is one group of heavy chain this is another type of okay I'll make it a diagram and then I will explain that why I'm making it like this these are just I'm drawing the heavy chains how many types of mainly heavy chains uh our B cells can produce mainly five types even though there are subgroups also we'll talk about that one two three this is the fourth and fifth group right so these are the types of heavy chains which can be produced and the light change which can be produced for only two the Kappa and Lambda now antibodies are classified according to the heavy change into how many classes five classes because mainly five types of heavy chains can be produced so if you put all my antibodies in the table and if you can look at their FC portions FC portions are made of heavy chains FC portions are made of heavy chains how many different types of heavy chains you will find primarily five is that right so we'll say they are basically five types of heavy chains and five types of sci-fi classes of amino globulins primarily is that right but light chains are only of two types Kappa and Lambda heavy chains are like suppose this heavy chain is called gamma chain this heavy chain is called Alpha chain suppose this heavy chain is called mu chain this heavy change is called Delta chain and suppose this heavy chain is called Epsilon chain this heavy chain is called Epsilon chain so basically antibodies can be classified depending upon the type of heavy change into five classes but if you look at their light light change there are only two types of light light chains there are Kappa light chain suppose this is Kappa light chain and another is Lambda light chains actually if you remove all the antibodies with the gamma heavy chains some of them will be having Lambda light chains of course held together by disulfide Bond and some of them will be having Lambda heavy chains light chain sorry light change is that right so actually Kappa and Lambda light chains are present in every group so we can say some of the molecules in every group will be having what is this the appaloid change and some of the molecules will be having Lambda light chains is the right and of course you are so intelligent all of them are held together by disulfide bonds there is no need to make it you understand it it means if you have these five group of antibodies or five classes of antibodies why the antibodies in different classes are different because they have different heavy chains and why antibodies in different classes have some similarity because they have same light chains again listen we say that antibodies are basically having five classes why we divide the antibodies into five classes that classification is depending upon the types of heavy chains is that right so in one group in any one group suppose we talk about this group if we take antibodies of only this group all the heavy chains will be same is that right but some light chains will be Kappa and some light changes will be Lambda so when you study in comparison group to group why groups are different from each other because they are having different heavy chains but they do have some physical chemical characteristics which are similar and they are due to light chains am I clear no problem up to this now those antibodies which are those immunoglobulins which have gamma heavy chain they are called IGG those Amino globulins which have Alpha heavy chain they are called IG a those immunoglobulins which have gamma heavy chain they are called IG G sorry this is Mu so they are called i g m and those immunoglobulin molecules which are delta chain Delta heavy chain they're called I G D and those Amino globulins which are having Epsilon heavy chain they are called IG that is why we say there are five classes of the immunoglobulance because the five different types of primarily heavy chains then later on you will learn that there are two subclasses of IgA that is IG A1 and IGA 2 and in the same way I G G can be divided into four types the minoglobulin G1 men of globulin G2 immunoglobulin G3 and amino globulin G four is that right any problem up to this so these are the subclasses IGG has four subclasses IGA has two sub classes no problem after this now let's go into detail of every class one by one we'll start studying now in detail every subgroup first of all we'll discuss about IG m important points related with immunoglobulin IG and IGM of course you will tell me that IGM has what type of heavy chain mu type of heavy chain now another question which I want to make it clear against before I really go into detail of classes let's suppose you have a bacteria and on this bacteria one bacteria has only one type of antigen or one bacteria may have many types of antigens one bacteria may have one type of antigen or one bacteria may have many different types of antigens yeah one bacteria suppose this is one bacteria it may have star antigen it may have ball antigen it may have triangular antigen it may have square antigen actually one microbe may have different types of antigens that is why we say microbes are antigenically mosaic right every microbe has multiple type of antigens now of course the antibody which is made against a microbe that will be one class one type of antibodies or multiple type of antibodies again for example this bacteria enter into your blood or in your body suppose this is E coli okay this is spherical so it cannot be E coli it is staphylococcus staphylococcus aureus it enters into your body and your you will build an immune response right this immune response will have antibody directed against only one antigen or antibodies will be produced which will be against multiple antigens multiple antigens so there will be anti-star antibody there will be anti-gola antibody or anti-ball antibody may be anti triangular antibody anti-square antibodies what I'm saying that against a micro which has multiple antigens it is quite possible that you will build immune response against multiple antigens this type of immune response is called poly Colonial immune response one clone of plasma cell or B cell will produce anti-star antibodies another clone of pizza or group of B cell will produce anti-ball antibodies another group of B cells will produce anti-triangular antibodies or anti-square antibodies am I clear so usually against an organism the antibody responses poly Colonel right that microbes are antigenically Mosaic and immune response from a healthy person you know competent person is Holy Colonial immune response now another thing let's suppose we talk only about anti-star antibody let's suppose the star antigen coming to your body we are making anti-star antibodies this anti-star antibody will belong to which class it will belong to IGG or IGM or IGA or which class it can belong to anything against one antigen we may make IGM in the beginning and later on we can make IGG or even IGA this is very important concept extremely important against the same antigen at different times or simultaneously human producing antibodies of different classes now let me make this concept more clear to you let's suppose this is star antigen now these are suppose heavy chains are suppose mu heavy chain oh okay these are gamma heavy chains if these are gamma heavy chains then can you tell me which is the antibody which is reacting with the star which class of the antibodies reacting with the star if it is gamma IG this is IGG molecule because it is having a heavy chain belonging to gamma but the interesting thing is that that now heavy chain has been changed but specificity for the antigen has not changed is that right and now let's suppose it is Mu if it is this heavy chain is Mu then what is this antibody plus IG m let's suppose that this heavy chain is yes Alpha if these are alpha heavy chains then what is this i g a you see against the same anti-gen you can produce IGM IGG IGA are you understanding me right so against one antigen you can produce antibodies with different classes usually the first class of antibody which is produced is IGN and later on you produce IG G against the microbes in micro first time enter into your body you may you in the antibodies you use which heavy chain mu usually when antigen is entering in your body first time then plasma cells are making antibody on first exposure foreign new because they are using the MU heavy chain so anti class which is initially since the size against antibody is IGM but later on class switching occur the same plasma cell may start producing IGG now you may be thinking how it is possible have you ever thought of it how this class switching occur how one class of antibody switch to another let me explain very briefly later on we'll have a full lecture on class switching and genetic on suppose this is a plasma cell right this is the nucleus of the plasma cell let's suppose here are the genes for the heavy chain you know in the heavy chain this is a portion this will make which mu when this part of the genetic material expresses itself you make with chain which heavy change you make new and when this start expressing itself you make which heavy chain Delta and when next Gene let's suppose this Gene start expressing itself what is this gamma so this is the gene for Nu this is the gene for Delta this is the gene for gamma and this is the gene for Alpha and this is the gene for Epsilon is that right now these are the genes which are present in every plasma cell to synthesize a special type of what heavy chain is that right now let's suppose this is a special part of Gene and this part of the gene is concerned with the heavy chain variable and this is heavy chain constant for the MU this is the heavy chain constant for the Delta this is the heavy chain constant for the gamma this is this Gene is for heavy chain constant for Alpha and this Gene is for heavy chain constant for Epsilon now you'll listen very carefully when first time antigen come right this part of the DNA will combine with the MU so antibody which will be formed that will be suppose this part of the DNA makes the variable portion of constant which will react with star now this is suppose make the peptide in the heavy chain which will react with bind with the star antigen is that this is the genetic component of the B cell or plasma cell it when it translates into a peptide fragment that piece of the peptide will become the variable portion of the heavy chain which will react with a special type of antigen which is suppose star antigen now what really happens initially this fragment fuses with this and both of them come together and start making heavy chains so in the beginning the heavy chains which are made in the cell they will have this portion with this portion and what is this this will be actually if I really put it like that what is this this is a heavy chain for the IGN is that right so in the beginning this cell will be making heavy chains for the IGM and the antibodies which will be produced of course what will happen just heavy chain with another mu heavy chain with two let's suppose chappa and what will this become whole molecule will become IGM molecule and it will be secreted out but if antigen again and again come and exposure become prolonged or repeated this will be digested away and thrown out it will change its strategy and this portion will this portion will fuse with this one both of them are thrown out both of them are thrown out Loop out and destroyed now the combination will be made VH with gamma now the heavy chain which is made now this is having this you know this Gene and this Gene fragments will come together and new combination will make the peptide chains right which will still bind with the star it's bind with the same anti gen but of course these are the light chains but heavy chain has been changed the constants of the heavy chain has been changed and the class of the antibody has switched from IGM to ig G your understanding so against the same antigen plasma cells are initially producing IGM later on they switch the class and start producing ID G so against the same bacteria and against the same antigen initially you may produce IGM and later on you may produce IGG or you may produce IGA no problem into this is that right so this is the concept of class switching because the function this this portion of antibody is different from class to class right but this portion of antibody may be same for a given anti-gen even classes may be different mclared and due to this reason whenever you get recent infection in your blood against that infectious agent IGM level will go up but if infection is repeatedly there then IGG levels will also go up so if you are having some disease right and I checked your blood and against an antigen you have only IGM it means you had recent infection but against another disease I checked your blood and I find IGG but I do not find IG M it means there were some previous infection are you understanding and if I find against a bacteria IGG and IGM IGM mean infection is going on IGG mean it's quite long time you are understanding it so it's prolonged infection again let me tell you something if this is my friend this marker is my friend against a bacteria it has only IGM it means it got bacteria recently this is my friend against the same bacteria it has only IGG probably it has previous infections this is my friend against the same bacteria IGM and IGG both it means he has infection from long time that is why he has IGG and still it is present in his body and he is still making IG and am I clear it is quite possible it is quite possible someone who is against a specific antigen IGG and IGM may be IGG represents the past infection and IGM will represents recent infection am I right no problem up to this here now we go to details of the entry body classes now we'll go to the IGM molecules first of all we'll discuss IGM class of the antibodies or amino globulins the very important thing that IGM is normally expressed on the membranes of the B lymphocytes this is a b lymphocytes and on the surface of the B lymphocytes IGM molecules are expressed what is the purpose of expressing the monomers of IGM on the surface of B cells will emphasize I will be impressed if you can tell me okay let me tell you before you tell me something new so this is one B cell this is another B cell this is another B cell right let us pause this B cell is presenting IGM on its surface and this IGM can bind only with the wall antigen right this B cell is presenting IGM on the surface and this IGM can bind with the star antigen this is another B cell and this B cell has IGM molecules which could bind with Square antigen actually every B cell in your body expresses IGN molecules on their surface and different IGM molecules on the surface of the different B cells bind with different antigens let's suppose these three B cells are there and there is no antigen and these three B cells are there in your body if star antigen come this will be activated if ball antigen come only this will be activated a square antique income only that will be activated actually there are millions and millions of the B cells having special type of IGM on their surface and these igms are going to act these IGM surface IGM molecules are going to act as a receptor for the receiving molecule receptor for the antigen that is why these surface IGM molecules are called B C R B cell receptors for the antigens so next time someone say that B cells are having receptors for the antigens most of these receptors for the antigens are actually IGM molecule some of these may be IG D molecule so IGM mainly and sometimes igd igd also act as B cell receptors right so actually different B cells have a capability to produce different type of different B cells have a capability to produce antibody for which are specific for different antigens all B cells cannot make antibodies for same antigen is that right so actually every B cell on its head is having a sample antibody having a sample antibody so actually antigen goes and bind with the relevant and then that B cell will be activated and converted into plasma cell now if star indigen come only this B cell will convert into plasma cell but if scare antigen come do you think Square antigen come do you think this will be activated now that will be activated right so what really happens that antigens come and bind with the only those be that B cell which is having such IGM or igd molecule which can react to a specific type of antigen so we can say one function of the IGM molecule is that they act as antigen receptor on the membrane of B cell and their IDM molecule is present as so these are acting as BCR so this is one important action of IGM right but IGM is not only present on the surface of the B cells which is called surface IGM or membrane IGM or B cell IGM they are monomeric but actually IGM molecules are actively secreted by plasma cells and IGM molecules are present also in your blood in your serum and serum IGM is pentameric they are not monomerate right suppose this is your blood this is your circulation in your circulation let's suppose this star is the J chain and how many IGM will be there one two three four and five right so basically IGM molecules are present in our serum or plasma as pentameric molecule which are joined together by the J chain is that right because they are large molecule they are mostly present in the blood they are not present in interstitial fluid and they are not part of other body fluids IGM is mostly distributed in plasma is that right this is the another thing that IGM here it is pentameric but it is deca valant I told you IGM is the first antibody which is produced during the immune response to a new antigen right such immune response is called primary immune response when first time you get antigen and you develop antibody we say it is primary immune response but if antigen is coming repeatedly then you are developing more immune responses after the first immune response whatever later on immune responses come they are called secondary immune responses let me tell you here that let's suppose you are vaccinating a person you're giving vaccination this first vaccination second vaccination dose third dose during the first dose you will develop gradually IGM but then IGM level will go down but with every dose it may go up but during the first response the IGG will be very last and second response IGG will become very high third responses will become very high now listen this when antigen first time enter into your body you develop an antibody response after some delay after some Delay from here to here there was no antibody gradually it started this is called lag period what is it called lag period so when first time antigen comes there is a long lag period and then antibodies will start appearing in the blood very slowly is that right and they will go a very low level of peak and then gradually they will come down this immune response is called primary immune response and in the primary immune response main antibody is IGM and IGG another antibodies are very less but if you repeat the okay I'll make it more clear let's suppose first dose second dose third dose of vaccination first response is right this is IGM so you see with every time antigen come there's a little bit IGM response is that right and initially this is first response but IGG response this is very little in the beginning second time it is very rapidly going up goes to a peak stay for a long time let come down but not so much and then next dose third dose it goes very high and stay for very long high so actually we say with repeated antigenous Square IGM is not boosted but IGG is boosted is that right so when you give me Star integent first time I will have mostly anti-star IGN but very little anti-star IGG but after a few months you repeat star antigen then I will have still little IGM but lot of and this time it will come very rapidly it will go very high level and it will come down and stay on the high level right this type of response is called secondary response but this type of response is Primary Response so on first exposure of the antigen antibody level go up slowly goes to a very low Peak and gradually come down and persist at very low level but on repeat as per year antibody level goes very rapidly very high achieved very high level stays there for longer time and come down slowly right on every repeated Square this will behave a very briskly antibody level go up and stay very high for longer time this first response is called Primary Response the second response is called secondary response and this third response is called yes Dr Safa it is not called tertiary first response is Primary Response after that every repeat exposure is secondary response characteristics of Primary Response are long lag period very few antibodies formed and it comes up down and stay very low this is Primary Response and Main antibody is IG n but in secondary response there is and secondary response would happen yes there is short lag period very rapidly Rising antibody level very high peak is achieved which stays for longer time and come down but stays at higher level this type of pattern is called secondary response ah secondary response is main antibody of IG G Class why it happens so look and first time some plasma cells started they were mainly producing IGN you know bone marrow is producing the B cell after six months when second dose come some new B cells have come they again produce IGM then after one year again expo here occur then again some Newcomb and IGN but from where the IG comes IGG comes when these first IGM have done class switching so next these are called memory cell so next time for antigen come previous memory cell very rapidly bigger response so these are the rapid response by the memory cell which were in the previous four year IGM producing cells now they are producing IGG when you come third response then memory cell from here and memory cell from here both of them respond so every time when you're boosting you are increasing the memory cell against the antigen and these memory cells are having what capability to produce more and more IG G that is why IGG keep on getting boosted with every response but IGM does not get boosted am I clear no no problem up to this now we were talking about that so we can say that igms surface IGM which is acting as B cell receptor number two there is serum IGM and about serum IGM what you should know that it is pentameric yes pentameric there are five monomers of IGM kept held together by J chain and this is DECA Valiant Deca valent because it can bind with how many antigens then so it is having less acidity or very high acidity it has very high ability is that right so because of another thing because it is DECA balance and it can react with multiple antigens now you imagine let's suppose this is IGM against your antigens on rbcs if this is IGM pentamer against the antigen on rbcs it will react with one RBC or multiple rbcs and one RBC may be reacting with multiple pantomers thank you so what is happening so multi what really happens that are you understanding what is happening the network rbcs which which were originally separate from each other as soon as IGM pentamers come they cross link them and these rbcs clumped together this reaction is called a glutination so IGM can react with multiple antigenic particulate matter particles so it will agglutinate the particle so it can agglutinate the rbcs if there are multiple bacteria let's suppose these are the bacterias and you know every bacteria has multiple antigen of one antigen multiple antigen and every for example this bacteria has three type of antigens and every antigen is multiple copies so if there is IGM so IGM will react against this react against this react against this so all these are what is happening to them they are cross length these bacteria are cross length so we say bacteria are a glutinated so we say that IGM antibodies a glutenating antibody that if there is some antigens which are in particle forms which will make the aggregate Aggregates of party curls right so number one IGM is act as B cell receptor IGM in the blood is or Serum is pentameric with decavalent and it is a glutinating yes A glutinating what antibodies these are agility netting antibodies and of course you will remember this is antibody of Primary Response or secondary response Primary Response its antibody in Primary Response IGM is the main antibodies the secondary response it is far less than IG Amic layer then another thing about the igms that IGM can activate complements right you know complement proteins are produced by the liver right and IGM can activate the complements there are two antibodies classes which can activate the complements by that that number one is IG G and number two is IG m because IGM antibodies is the five groups held together by J chain actually these FC portion of the IGM can bind the complement proteins with them and they can activate complement this is C1 and C1 can activate C4 C2 you know it then C3 C5 six seven eight nine so this pathway of complement activation where antibody FC portion can bind with C1 4 and 2 and activate the complement pathway through this pathway this is called classical complement pathway activation what is this classical activation of the complements so IGM has one more function what is that this is complement pathway activation but there is one thing the FC portion The receptors for FC portion of IGM are not present on our cells so IGM cannot bind with our cells let me tell you if there are the bacteria here how the IGM is going to kill IGM can kill the bacteria or destroy the bacteria by activating the complements let's suppose here is IGM of course now this group of IGM will activate the complement C1 4 2 c 3 5 and 6 7 8 and 9. you know c5b 6789 this is called membrane attack complex resistible study in detail in complement system activation so c5b6789 this complex will puncture the membranes of the bacteria and bacteria will die right but IGM FC portion cannot bind with neutrophil the macrophage cells why because the FC portion does not have receptors of on the phagocytic cells so it cannot optionize the bacteria you know opsonization is a different concept opsonization mean that let's suppose here the bacteria here's antibody molecule antibody molecule on one sign bind with the bacteria on other side antibody molecule has a receptor on a this is a receptor for on a suppose what is this cell suppose this is neutrophil of macrophage so on the surface of neutrophil or macrophage if there is a receptor for FC portion of the antibody and an antibody on one side catches the bacteria on other sides binds with the neutrophil of macrophage can now this bacteria run away it is caught and then very effectively it will be phagocytosis this bacteria cannot run away is that right because there is an antibody which can bind on one side with the bacteria and other side with the phagocytic cell right in phagocytosis of this bacteria is facilitated in the presence of this antibody such antibodies are called opsonance what are they called IGM is not opsonin because if IGM bind here IGM cannot bind with the phagocytic cells this is IGG so antibodies belonging to ig class actors option but antibody belonging to IGM class can not act as obso nen is that right so about the IGM just important points number one IGM is monomeric right and present on the B cell surface as B cell receptor in the serum IGM is present as pentameric decavalent large molecule mostly in the plasma circulation right because they are trapped in that not in the other body fluids and significant amount and ID IGM is pentameric with Deca valent molecules and it can produce agglutination reactions is that right it can activate the complement by the classical pathway and of course we should remember IGM is the main antibody of the primary immune response is that right do you have any question up to this so let's have a break so we were talking about the classes of antibodies or classes of amino globalance and we have already discussed that primarily there are five classes of immunoglobulance one way to remember is g a m e d gained Games stand for what immunoglobulin G minoglobulin a minoglobulin m immunoglobulin e and immunoglobulin D already we have discussed in detail about immunoglobulin m right now we will talk about immunoglobulin G why minoglobulin G is called Mino globulin G because the heavy chains in the immunoglobulin G belong to the gamma group is that right now what are the important points related with Amino globulin G Amino globulin G is number one it is the most abundant immunoglobulin in your body most abundant Amino globalized you know why because with repeated infections immunoglobulin G keep on accumulating right you must be knowing that immunoglobulin g is the antibody of secondary yes response again as we mentioned previously that let's suppose this is the time here is a minoglobulin concentration if there is a repeated exposure this is suppose first exposure second exposure third Square to the same antigen so initially the immune response which will come that is called primary immune response after that there is secondary immune response and with repeated exposure there is now another secondary immune response again I will repeat as I mentioned previously there is a big difference in primary immune response and secondary immune responses right why number one in the primary immune response there is a slow and gradual increase in antibody concentration and it reaches to the Peak at low level and gradually come down to very low level and the main antibody in the primary immune response is IG M this is mainly IGM right uh in primary immune response concentration of IGG is very low right but with every new expo here suppose this is our second exposure now when the antigen come second time in your body it will find some of the memory cell right which which were activated in the previous response and those memory cell will rapidly proliferate and give very strong antibody formation response and now the antibody will be dominantly IG J right but during this time right after the first expo here for example after some time when the second exposure will occur during this time from the bone marrow some new B cells may have come and they will be taking the second exposure as their first you are getting it and they may produce what another IGM production so what really happens with repeated Square with repeated exposure IGM is produced with every exposure right but in the primary exposure on the first of all year IGM is the main antibody as far as IGG is concerned IGG is during the first expo here made in very small amount but with repeated exposure concentration of ieg G keep on increasing why the concentration of IGG keep on increasing because the cells which originally made IGM now they have switched they have done the class switching and they have started making IGG when there is a repeated exposures it means during every expo here some plasma cellular B cells and plasma cells are made and they initially make IGM and then switch to IGG so when you have repeated exposure to the antigen you have a lot of B cells memory B cells which are ready to produce lot of IG is the right another thing which is very important to remember half-life of IGM is short but half-life of IGG is long that is why if you get uh antigen today you will make IGM right but gradually IGM will this uh Universe Half-Life is less so gradually it will its levels will go rather not gradually rapidly in your blood the IGM level go down but in repeated exposure when you make IGG because its Half-Life is longer it will strain your body longer time am I right now let me mention one thing again that what really happens that if I get infection today first time then against that antigen I will be making IG M right but if I got some infection five years back and again I get the same infection today then I will make IGG because I have a previous exposure and previously uh you can say previously trained memory cell will be reactivated and they will produce IGG and some new B cell will also be recruited and they will produce IGM so what really happens it's a very important concept that if against an antigen you have high triggers of IG m in your blood it means that infection is recent but against another infection if you are having only IG mainly IG in your blood then it means this is the past infection but if you have right now in your blood against a microbe IGG as well as IGM it means that you had previous exposure to that organism as well as you have current exposure am I really clear right so what I'm talking about IGG is the most abundant antibody present in your body number two it is the antibody mainly in the secondary response right thirdly IG G is present as monomer it is monomeric again keep on comparing my number keep on keep on comparing with the IGM look IGM was the third most abundant in the blood the first most abundant is IGG then second most abundant is IGA and third most abundant is IGM again uh the concentration of antibody in the blood decreases according to the sequence of alphabets in gamed that IGM IGG has the highest concentration of the antibody IG has less than that IGM is more or less IG is very less and igd's in traces you get it so keep on comparing when we are studying IGG with the IG M that IGG is the most abundant IGM in the blood is less number two IGG is antibody of secondary response but IGM is antibody of yes Primary Response is the right then IGG is as a monomer but IGM is present in the blood as pentamer right IGG circulating the blood in as monomer so we can say that it is having two heavy chains and two yes light chains and heavy chains belong to gamma and gamma is that right because it is a small molecule so not only it circulating the blood this also comes into other body fluids right so IGM is mainly in the blood IGM is mainly in the blood IGG is in all body fluids but IGA which we'll study later it is specially secreted in our body secretions that's the right IGG is not present in our body secretions in much amount right okay it's because it is monomer so it must be dye it must be die violent is that right now another thing which is important about it is that it crosses placenta it crosses placenta so it means that on the placental cells you know placental cells Express The receptors for FC portion of IGG let's suppose here is placenta and here is your fetus right now what really happens that the cells on the placental surface the cells which are facing to the maternal blood they express The receptors for FC portion of IGG and so IGG from the maternal side from mother blood IGG bind with these receptors and once these receptors are loaded with IGG they undergo endocytosis process and then and through the final cytosis and endocytosis they are transferred from maternal blood side to the fetal blood side so mother is giving a very precious gift to the baby what is the gift IGG so IGG basically is a special maternal gift to the baby so when baby will come to the world he will have lot of IGG from his mother why IGM is not given to the baby and IGG is given is there any special advantage in giving IGG and not IGM no no no mother gives very big things to the baby now look let's Suppose there is a Japanese mother who has come to visit America and she is living in America for few months if she's if she gives only IG M to her baby she will give only those protection against those infections which she currently suffer you're getting it but if she gives her baby IGG then in her blood she has IGG against almost all infections she suffered in her life and Julie baby live in the same environment in which mother lives fathers are a bit different thing right so what really happens that mother this is the best gift they give gift they give to their babies that mothers have the pool of IGG or every person has a pool of IGG antibodies directed against many many microbes for which we have been exposed in our past years you are getting it so if a mother is giving IGG to her fetus so she is giving immunological protection to the fetus against many many infections not only against the current infection but also in her past infections but if mother could give only IGM then she mother will protect the baby against only against the current infection is that right so it is a superior strategy which has evolved during Evolution that human females give to the baby translucently their own IGG the pool of IGG if a woman is living in Africa right she will have different pool of IGG woman who is living in USA she will be exposed to different infections in her life she will have a different pool of IGG and woman who is living in India she will have she has been exposed to different uh set of infections and she will have different types of IGG in her blood so all these three mothers will give their fetuses different type of pools of IGG which are best suited for for the baby protection once they take birth there's a logic in that am I right okay there's I want to there's a very important concept if a baby is born and baby is having IGG against the syphilis newborn baby has IGG antibodies against the syphilis but baby does not have any IGM against the syphilis do you think baby has been exposed to syphilis trypanema playdum or not let me repeat a question a newborn baby has IGG against the triponema Platinum the causative organism of syphilis but that new bar baby does not have IGM against the cephalus what do you think baby has been exposed to syphilis organism or not no probably mother was exposed to the syphilis somewhere in the past and she had a anti-trepreneurial IGG and she passed it to the baby but if during the pregnancy mother is suffering from stress during pregnancy and tripone apply them uh through trans placental route tripone apply them from maternal blood goes to the baby and fetus and baby gets the organism of syphilis such baby if he takes birth right in such baby's blood you will find IGM directed against so a newborn baby if newborn baby has preformed IGM against an organism which means it means that baby was exposed to that organism during intra uterine life am I clear but if a baby has Iggs against multiple organisms then it means probably these IGG not sure it is IGG molecular coming from maternal side so IGG is most abundant it is antibody of secondary response it exists in monomer so it is divalent and it crosses placenta very efficiently and how it works number one it can activate complement activate complement system complement system by classical pathway classical pathway let me tell you what exactly is meant by this let's suppose here is a bacteria okay let me let's suppose here is a bacteria and these are bacterial antigens and you are having IGG antibody right and as soon as IGG antibody bind with the antigen its absolute portion become active and now it can activate complement so IGG can activate complement number one c one two 4 3 c 3 a will go away c 3 B will be there then C 5 b c 5 a will be away and then C6 yes 7 8 and 9. right this is membrane attack complex this much right so basically uh IGG antibody once it bind with the antigens then its FC portion is activated which can activate the complement by classical pathway and kill the microbe this is one way secondly IGG can act as option n now what is meant by optionization and option and actually when IGG bind with the bacterial antigens its FC portion become active and neutrophils and macrophages are having membrane receptors for the active FC portion of IG J so if this is a neutrophil then neutrophil will have receptor for the active portion of right this is a neutrophil and neutrophil had this specific receptor and this receptor could bind uh with the active portion of IGG so IGG on one side is holding the bacteria of course bacteria is very sad right IG is holding on one side bacteria and other side it bind with the neutrophil now bacteria cannot Escape right and this receptors give signals into phagocyte and these signals stimulate the phagocytic process so actually when IGG bind on the part particulate matter for example bacteria it enhances the phagocytosis of these particulate matter of bacteria right this process is called opsonization what is optionization optionalization is a process in which obstinin molecule bind to a particulate matter on one side they bind to the particulate matter which may be bacteria or a cell another side they bind with the phagocytic cell and they facilitate the process of Phagocytosis right so IGG act as option n so IGG can kill the bacteria by activation of complement or IGG can help the neutrophil and macrophage to very effectively phagocytose the bacteria which are molecules plus IGG molecule can neutralize neutralize yes what neutralize viruses virus and toxins now what is the concept of neutralization of virus yes Dr Safa you will tell me something have you heard of this term there are some antibodies neutralize the viruses or toxins okay let me explain let's suppose this is the target cell right and this is a specific virus suppose this is a virus and this virus is going to attach with this cell and push a genetic material in actually on the surface of the virus there are special type of proteins and these proteins help the virus to bind with the target cells right on the target cell there must be receptor proteins and let's suppose this protein of the virus will bind with this cellular protein so virus will bind here like this right and when these for two proteins interact then virus will be taken in or virus genetic material will be going in so first step for virus to attack our cell is that virus should develop attachment with ourselves once virus is attached then it will push its genetic material in is that right IGG antibodies actually bind on these proteins and block them if IGG antibodies bind with these proteins do you think now virus can bind here no so we say capability of virus to bind and invade our cell has been neutralized by the presence of IGG this is the concept of that some antibodies can neutralize virus of course IGG is one of the very important in the same way there are some toxins right let's Suppose there is a toxin which has a component and it has one more component which is called B component many toxins which are produced by bacteria they have a component a for Action which produces action in the cells toxic action in the cell and B is for binding for the cell so let's suppose this is receptor for the toxin this is receptor for the Toxin and actually B component binds here and only then when b b component of the toxin bind with the receptor only then a component will be translocated into cell and then a component will do toxicity in the cell actually some of the IGG antibodies they bind with the B component and when they bind with the B component can be component bind with the receptor of the target cell and can toxin enter into cell so capacity of toxin in the presence of IGG against its B component right then capacity of the toxin to enter into cell has been neutralized so this is how we say that this is a neutralizing antibody because it can neutralize virus and toxins mclear again you must compare these function with the IGM antibody IGN could also activate the complement so complement can be activated in a classical pathway by IGG as well as by IGM right option in function of direct optionization is done by IGG but direct optionization is not done by IGM because I there are no receptors on the phagocytic cell to bind with the FC portion of IGN so IGM cannot directly optionize the bacteria but IGG can directly optimize the bacteria then neutralization of virus and toxins IGG and IGM both can do this function another thing which is there that IGM could do what agglutination you remember IGM was as pentamere with Deca violent it could bind with multiple particulate matters so IGM could work as a glutinating antibody but IGG because it is only divalent can It cross-link many many cells or particulate matter no so IGG cannot do a glutination reactions IGM can do but IG G cannot do agglutination reaction but IGG can be involved in precipitation reaction precipitation reaction mean that in a test tube you have put the antigens there are many many antigens and then you add from uh you add to this IGG iggn antigens may make what is this they may make antigen antibody complexes and because this is the small compactors so they may settle into bottle right so they play a role in precipitation reaction so IGG can play a role in precipitation reaction but IGG cannot play a role in in agglutination reaction IGG cannot play a role in a glutination reactions agglutination mean that antibody should cross length multiple particulate matter right like multiple bacteria cross-length and clumped or multiple rbcs are clumped this is a function of pentamers of IGN is that right so these are a few words about IGG now we will talk about IG a now IGA do you think IGA antibody it is the second most abundant antibody in your blood but the very special thing about IGA is that not only it is present in your blood but in large quantities ige is also present on all mucosal lining of the body and in all body secretions right so that makes IGA very very important antibody let me explain let's suppose that this is uh git and this is a jit mucosal cell and here is your blood circulation and let's suppose here you have a plasma cell is that right these plasma cells are producing i g a right now when IGA is released now let's suppose either I G A and T bodies sum of the IGA which are released they are held together by J chain they are held together by J chain so it means they are released as Dynamic form but some of the IGA is released as these monomers will be going to the blood so you must remember I G A circulate in the plasma in a monomeric form IGA circulate in the plasma as monomeric form or this IGA is also called IGA 1. right so but it they are not cross linked by the J chain but this these two molecules of monomers of IG a which are held together by the joining chain and this is now becoming a dimer this dimer is internalized by it enters into what is this cell mucosal epithelial cells right and once IGA diamonds are inside IG a dimers are inside already they were joining with which chain then uh epithelial cells of mucosa will produce another protein which is called circulatory component and circulatory component also bind with that circulatory component so security component is of small protein which is synthesized by mucosal cell and this binds with the IG a dimers and then secretary component help it to the whole complex to go to the Lumen So eventually this dimer of IG a right with the two join in and one what is this circulatory component all this complex is secreted on the mucosal lining right these IGA are very good molecules because whenever virus or bacteria they are coming those viruses will bind here and then of course they cannot invade the mucosa so many antigens which are coming uh to the mucosal lining those antigens or virus or bacteria they will bind with the pre-formed and pre-secreted IGA and in this way they will be neutralized and they will not be able to invade in our cells is that right that is why IGA is said to be antiseptic paint of our mucosal Linings this is also called that IGA molecules dimers are antiseptic paint on our mucosal Linens right ah it means let's put it there the important information IGA this is the second most abundant antibody in the in our body right secondly it is present as monomer in our yes it is present as monomer in our blood it is present as dimers and yes dimers and mucosal surfaces plus body secretions number four that IGA right this is present in which mucosal membrane every mucosal membrane throughout the gastrointestinal system it is painted with IGA urogenital system it is printed with IG a your respiratory system all respiratory mucosa is painted with IGA even your conjunctival mucosa is printed with IG a so it's a mucosal defense mechanism against the invasion of many microbes right secondly which secretions all the body separations all respiratory secretions gastrointestinal secretion urogenital secretions even in the tears in the saliva in the milk and specially colostrum has a large amount of IgA actually uh this is very interesting and very important to know there will be newborn baby is born babies having lot of IGG molecules transferred from the placenta to protect the baby against men infections but after the birth if mother is breastfeeding then baby is getting lot of IgA from Eternal milk and this IGA will line the babies get mucosa so that if some bacteria or virus come to the baby's gastrointestinal system they will be neutralized is that right but mothers who are not doing breastfeeding their children have more often uh gastrointestinal infections and diarrhea because uh the formula milk which are coming they are not bringing IGA in that is that right so it is in high concentration applied on the mucosal lining it's in higher concentration present in the all body secretions including milk and colostrum and then another important thing about IGA is that it does it does not activate the complement by classical pathway but it can activate the complement by alternative pathway so classical pathway complement activation no IGG or IGM could activate the classical pathway but iega does not activate the complement by classical pathway but it does activate the complement by alternative pathway it can activate the complements by alternative pathway after this IGA now we talk about igd and ige so let's talk about ige IG is the class of immunoglobulance which are having heavy chains belonging to the Epsilon group Epsilon group ige body is produced in small amounts as compared to the IGG IGA and i g m right IG is in the blood in very small amount both of them are in traces in the blood now ige once it is formed it loves to bind with the mast cells and Diesel Fields ige is also called cytophilic antibody cytophilic antibody mean it loves the cell right for example once ige is made well this is ige again it has two heavy chains and two light chains held together by disulfide Bond so ige exists as monomer with divalence but most of the ige right now which is present in your body that is bound with the mast cells because mast cells have receptors for FC portion of ige but when antigen bind here only then this FC portion become active stimulate the mast cells and when mast cell is stimulated you know when a allergic substance actually when we say that for example if you have allergy to penicillin and you have made anti penicillin ige antibodies then ige antibodies will be loaded on the mast cells and when allergen come bind with the ige antibodies actually allergen usually cross link multiple ige these are the ige entibodies which are previously formed and loaded on the mast cell receptors when the allergen come suppose this is an allergen right it will activate bind to the multiple IG e molecules on the mast cells and they will come together and then they will give signals to the mast cell and Mast Cell will be activated number one signals will go to the membrane and from the membrane there will be release of prostaglandins and there will be release of Lego trains plus there will be release of lipoixens right plus there will be released from the membrane of platelet activating Factor so what really happens that when ige is activated on the surface of mast cells or basophil basophils are circulating into blood Mass cellular connective tissue cells present in your connective tissue throughout except central nervous system central nervous system does not have mast cells so when ige is loaded on the mass algeet activate number one the membrane then from the membrane lot of chemical mediators of inflammation are released like prostaglandins leukotriene lipoxins and platelet activating Factor plus they give signal to the cytoplasm and these signals when they come to the cytoplasm number one to the membrane number two signals are going to cytoplasm they activate the granules and Mast Cell degranulation releases yes histamine do you know that histramine fiber hydroxy tryptamine plus it releases proteases proteolytic enzymes plus it releases yes neutrophil chemotactic factor and eosinophil chemotactic Factor so what really happens once allergic substance bind with the ige which is all already loaded on the mast cells muscle membrane activation releases lot of inflammatory mediators as well as Mast Cell cytosolic granules release also produces chemical mediators which enhance the inflammation and if even signal will go to the nucleus and nucleus will lead to formation of new which will translate into proteins and some proteins will be secreted out which are actually cytokines like it will never release in tumor necrotic factor or interleukin-1 so ige plays a very important role in activation of the mast cells and basophils during a type 1 hypersensitivity reactions during which all these chemical materials are raised into tissue and produce severe inflammatory reaction amicler then ige not only binds with the mast cells and base of Health but ige plays a very important role uh in defense against parasites especially helmets helmets elements for example against scares strong gay Lloyds or against neck hook worms against tricky Nila these are different type of parasites people who are infested with parasites they have very high level of ige ige which is directed against the parasite antigens that help us to kill the parasites for example if there is a parasite here right right of course these are the antigens of the parasites ige will bind on the parasite antigens and ige also has its receptors on the which what are these cells this is not Marcel this is eosinophils these are assinophils so what really happens that ige antibodies can coat the what are these parasites and their FC portion can activate the xenophils and then your sonophils will release very important destructive products and these destructive products have one important function which is called major yes basic protein and this major Pro basic product and then some other substances which are released by the granules of the sinophil they destroy the parasites right in this way ige helps us to kill our parasites right and the people who are having these parasites in their body or the larvae of these parasites these people have high concentration of ige and now we come to the last antibody group and last classes igd the good news about that is we don't know much about that this is present in the blood and very small amount in traces and it is present on the B cells as B cell receptors you remember B cell b lymphocytes were having on their surface IG m but there is also some IG D so i g m and igd are present in monomeric form expressed from the surface of the i b lymphocytes and they act as they act as receptors for the antigens so B cell receptor or bcrs are mainly IGM and some of them are IG D is that right so okay I will ask you some questions now we will talk about another way to type the antibodies antibodies can be classified as ideal types yellow types and isotypes another way to classify antibody is allo types allo types ISO types and ideal types now listen let's suppose here you are and from your circulatory system we remove all the antibodies we remove all the immunoglobulins now all the antibodies which we can bring out from one person they have something common right because antibodies are what antibodies are just peptide chains these are four peptide chains to heavy chains and two light chains held together by disulfide bond is that right and antibodies because they are protein so they are antigenic for example if your antibodies injected into a donkey suppose this is a donkey I don't know how to draw donkey but you can imagine it this is a donkey right and if human antibodies suppose antibodies from this person are injected into donkey these are the antibodies when antibodies will come do you think for donkey these antibodies are self proteins or foreign protein it depends on the person actually right human antibodies for the donkey are foreign proteins so donkey's immune system will take these human antibodies as antigens and Donkey the immune system will produce antibodies against human antibodies you are getting it so it means human antibodies are antigen because the proteins they have antigenic areas or we call them they have antigenic determinants is that right now actually they found that all the antibodies which are present detect are removed from one person all the antibodies which are present in one person they are having something common for example some minuset sequence here in the light chain and some minor acid sequence let's suppose here this amino acid sequence is present in all the antibodies of this person right so according to this concept that this person has inherited sir a special type of alleles and those special inherited alleles all the antibodies from this person have some minus or sequences which are common right and according to these amino acid sequences antibodies vary from person to person for example in my case in my all antibodies suppose here is histidine and here is leucine maybe in your case at this point there is histidine and threonine so my all antibodies have histidine and leucine and your all antibodies have suppose histidine and threonine so it means all my antibodies have same antigenic determinant here and all your antibodies have a different antigenic determinant here but for sure antibodies all of them will have the same antigenic determinant so this if we classify human antibodies according to this antigenic determinant we say we are doing allo typing so I have one allotype and you have one allo type so all the antibodies which are present in one person they have that that is determining that's one yellow type is that right opposite to that isotype means the differences in antibodies in the same person due to heavy chains you know the constant of the heavy chain these are the constant region of heavy chain how many different types of heavy chain one person is making mainly five types because these are the five basic classes so we can say if we bring all his antibodies out and try to classify his antibody according to constant of the heavy chains how many will be main group five so if donkey is going to make antibodies okay Donkey is going to make antibodies against the constants of the heavy chains how many types of antibodies you will make five types is that right so this when you classify antibodies in a person according to the constants of the heavy chain they are divided into five group and those groups are called isotypes what are they called isotypes so I have how many types of isotypes five and you have how many types of isotype five and my isotope and your isotypes are same this is very important you have IGG IGM igd ige IGA I have also same groups is that right but donkey does not have the same group for donkey will make empty isotype antibodies my antibodies into a donkey donkey will make how many types of anti-isotype antibodies five but donkey will make how many donkey will make how many types of anti-allo type one I have only one Hello type so if you inject my antibodies into a donkey the donkey will make how many anti-allo types one donkey will make how many anti-isotype five so one person has how many isotypes five or one person antibodies when they are classified according to allow typing in one person how many yellow types are present one if one person's all antibodies are classified according to the isotypes how many groups are there five thank God you know it now ideotype Ideo means unique idiom in Chinese actually if I have been exposed to thousands and thousands of many different virus and bacteria then it means I've made thousands and thousands of different type of antibodies with specificity for different antigens is that right and why now one antigen is let's suppose one antibody you know every antibody has different there's a special variable areas here variable area of the heavy chain and variable area of the light chain so that this antibody molecule must bind with a specific antigen now tell me one thing in one person if you try to classify if you try to classify all my antibodies according to the these variable regions how many antibodies groups I will have millions right this is say that every all the antibodies which are derived from which are made by one clone of B cells they have the same variable region but actually every person has capacity to make millions of different antibodies directed against different antigens so it means in every group of and every antibody these variable regions are so unique that every antibody will bind with a unique anti-gen or to be more clear all the antibodies which are derived from one clone of one clone of these cell they are directed against a unique antigen and all those antibodies will have a unique amino acid sequence here is that right now if you remove my all antibodies and inject into donkey and if donkey is going to make antibodies against variable regions of my antibodies he will make millions of different type of antibodies we say that he is making anti-ideotypes idiotypes so what is idiotyping idiotyping is the typing of the typing of the antibodies according to their variable regions isotyping is the typing of the antibodies according to the constant of the heavy chain allo type the striping of the antibodies from person to person right so because my every antibody which is directed against different antigen has a different type of Ideal type so what are ideal type ideotypes are the antigenic determinants made by the amino acid sequence in variable region let me repeat it it's worth repeating what is ideal type ideotype is the antigenic determinant pressure made by the amino acid sequence present in variable part of the antibodies and one person may have millions of ideotypes then isotype what is isotype isotypes are antigenic determinant and the antibodies of a person ah which depends on the amino acid sequence and constant of the heavy chain is that right and allo type is the antigenic determinant present in a person's antibody according to the allylic morphology right again amino acid so I can say that all my antibodies will have one point is unique which is unique to my all antibodies right so as far as this is yellow type so how many allo types I must have one how many isotypes I must have five how many ideal types I must have Millions is that right so when we say that there is anti-ideotype antibody it means that antibody will react here for example if donkey make anti-ideotype that will react here if donkey make anti-isotype that will react here if donkey make anti-lo type that will react here is that right any question right clusters

Channel: Dr. Najeeb Lectures

Views: 35,853

Keywords: medical lecture, dr najeeb, dr najeeb lectures, usmle step 1, immunoglobulin, immunoglobulin structure and function, antibody, antibodies, structure of antibody, igg, igm, iga, igd, ige, immunoglobulin igg, high ige level, antibody structure, structure of immunoglobulin, types of antibodies, immune system, immunology, mast cells, plasma cells, dr njaeeb new videos, antibodies structure and function, immunology dr najeeb, immunology lecture, anibodies immunology, igg igm igd iga ige

Id: UBPgySKEAG8

Length: 160min 33sec (9633 seconds)

Published: Sun Apr 30 2023