 different types of WBCs recognize the antigens differently. For example, when we talk about the neutrophils and macrophages which basically phagocytos the antigens they how they recognize is that there are certain receptors known as tall like receptors which are basically identifying certain patterns on the microbes right. So these neutrophils and macrophages identify the microbes by means of these tall like receptors also known as PRR that is the pattern recognition receptors. On the other hand, when we talk about equidiminity then we talk about the lymphocytes. So in lymphocytes we have B lymphocytes as well as G lymphocytes. While B lymphocytes have a antibody which is expressed on their surface and this antibody is IGT. So this IGT is important for the recognition of receptors on the microbes or the antigen. So these cells recognize the antigens directly by means of binding of these antigens to IGT. On the other hand, the recognition of the antigens by T cells is a little complex process which requires antigen recognition by something known as antigen presenting cells. And then these antigen presenting cells process the antigen and present it to T cells. So these antigen presenting cells present to basically helper T cells and there are other antigens as well which may be present in other cells. For example, it may be a virally infected cell. So the virus antigens are recognized by the cell and they are presented to the cytotoxic T cells. So let us see the details of how this antigen recognition and antigen presentation is happening to the T lymphocytes that is the helper T cells and the cytotoxic T cells. So for antigen presentation a complex of proteins is required known as MHC that is the major histocompatibility complex proteins or in humans also known as HLA that is the human leukocyte antigen and the name is given because it was first found on the leukocytes. So now these MHC proteins based on the structure of these proteins function and in which cells these are present that is the cellular distribution these are broadly classified into two types that is the MHC one major histocompatibility complex type one and MHC two. So let us see in detail what is this MHC one and MHC two. Basically these are glycoproteins which are formed from MHC genes and they have different structure. When we talk about MHC one it consists of alpha chains alpha chains okay which itself has three domains so there is alpha one alpha two and alpha three and if we see how it is present basically this alpha one and alpha two domain they form the extracellular part okay and there is a groove between this alpha one and alpha two and then there is this alpha three domain which is basically attached to the cell membrane and this alpha one and alpha two domain the groove which they form that is the antigen binding groove okay so antigen can bind here so only when antigen binds to this groove and it is presented by the cells to the t-cells then only t-cells will be able to recognize it. Now along with this alpha chain it binds with another protein that is the beta two microglobulin as well but this beta two microglobulin is not a part of MHC as such so that is the structure of MHC one. Now this MHC one is present in all nucleated cells okay all nucleated cells and in platelets also it is present even though platelets are not nucleated so all nucleated cells plus platelets. Coming to MHC two now MHC two consists of two chains that is the alpha chain and beta chain and both of these alpha and beta chain consist of two two domains that is alpha one and alpha two and beta consists of beta one and beta two. Now similar to that of the MHC one here also there is a formation of the peptide binding groove the antigen binding groove and that is formed by alpha one and beta one domain this is beta sorry so this is beta one domain so this is the chain alpha one and alpha two chain right and this is the beta one beta two domains of the beta chain and here they connect together and they form the antigen binding groove. So that is why MHC two is known as a heterodimer because it is consisting of two chains alpha and beta while if we see MHC one it has only alpha chain. Now in some books it is also mentioned that MHC one is also a heterodimer because it is being associated with another protein beta to microglobulin yeah that's a little controversy but remember that if there is a mcq then depending on the options which are present you have to choose the best possible answer. So we were talking about MHC two and we said that MHC one is present on nucleated cells and platelets MHC two is present only on antigen presenting cells okay not on all the nucleated cells all nucleated cells means that all the cells of the body which are nucleated right and here antigen presenting cells are the cells which have a specific function of presenting the antigen to T cells and these cells are B cells we said how they identify the antigen that is by direct recognition isn't it then there are macrophages okay and finally there are some specialized cells known as the dendritic cells and these dendritic cells are present in lymphoid tissue they line the various portals of entry of the microorganism so in lymphoid tissue they are present they are present in spleen as well then in skin they are present as langur hence dendritic cells plus there are some other types of antigen presenting cells also which may line as I said the portals of entry for example some intestinal epithelial cells can also act as antigen presenting cells now with this concept of MHC one and MHC two let us go into details of how the antigen is presented and how T cells recognize these antigens so first we will talk about MHC one how the various cells present the antigen now this MHC one as I told it is present on all nucleated cells so what is the use of this thing see any cell of the body can get infected or there might be some mutation which will produce some abnormal proteins so these abnormal proteins need to be broken down and the lymphocytes have to be told see there are certain abnormal proteins maybe by tumor maybe by virus that is affecting me so you recognize these antigens and do your job so what happens suppose this is a cell right and there might be some abnormal protein say suppose viral antigen now this protein is digested within the cell and whenever there is such kind of intracellular antigen intracellular very important these antigens are not present outside the cell is recognizing them inside only right so this is intracellular antigen and whenever such intracellular abnormal protein is there it is digested by means of the complexes of proteolytic enzymes known as proteosomes okay so proteosomes within the cell digest this antigen and then fragments of this antigen move to endoplasmic reticulum now in the endoplasmic reticulum there is also this newly synthesized MHC one so here there is a complex formation of antigen as well as MHC one okay so suppose this is the MHC one protein antigen comes and binds to this protein in endoplasmic reticulum then from the endoplasmic reticulum it is transported to the cell surface so what happens here is the MHC one and there is binding of this antigen on this MHC one so this is the antigen presentation now T cells should recognize this also which T cells will recognize this it is cytotoxic T cells which recognize this kind of antigen right cytotoxic T cells and all the T cells have T cell receptors so suppose this is the T cell this will have the T cell receptors for various antigen now we will come to the heterogeneity of the receptors at how various receptors are capable of identifying different types of antigens later little bit later okay so this is T cell receptor which recognizes the antigen now this MHC one as I told you is made up of what alpha one alpha two and alpha three domains and alpha one and alpha two domains make the antigen binding site this alpha three domain which is present maybe somewhere here it will be present it has a binding site for another protein that is CD8 remember cytotoxic T cells are also known as CD8 plus T cells okay so when a cytotoxic T cell comes in contact with this antigen by means of the T cell receptor this CD8 protein also makes contact with this this CD8 binding region of the alpha three domain so that is how the MHC one always presents to cytotoxic T cells only and not to help ourselves and why that is because of this CD8 protein which is present of the T cells so that is why cytotoxic T cells are known as MHC one restricted only when the antigen is presented along with MHC one then only they will be able to recognize the antigen otherwise they will not recognize and because of this the CD8 binding is also known as core receptor so there is a TCR T cell receptor and there is core receptor that is the CD8 protein now for activation of this cytotoxic T cell this is not enough this is only antigen recognition by the T cells but there should be activation also and that is done by co-stimulation so remember certain words I told about core receptor and now I'm talking about co-stimulation and this co-stimulation is by binding of certain other proteins so on the T cell there is a protein say CD28 receptor and its ligand is present on the cells which are presenting the antigen and there is co-stimulator proteins are there so these bind and there are various co-stimulator proteins are there B7 proteins CD8T and only when there is co-stimulation also then only there will be activation of the cytotoxic T cells and what it will lead to it will lead to basically killing of this cell which has presented the antigen to the cytotoxic T cell it will be killed and it is important also see this is not a WBC and it will not be able to kill the antigen it is just telling the T cell that I have been infected or there is some abnormal protein in me I'm not able to do the job properly so the cytotoxic T cell kills this cell and prevents the spread of the abnormal protein now remember one thing here that I have been telling you that there is two stimulation happening one is this stimulation and the other is the co-stimulation so this first one is known as the signal one and the second one is known as the signal two and both are required for activation suppose if only signal one occurs and there is no signal two then in that case the cell the T cell will inactivate okay so it is like that this is not a harmful antigen and that T cell becomes unresponsive to that particular antigen so this is fundamental of MHC1 presentation and recognition by the T cell receptors just one thing here remember that I talked about heterogeneity what is that that is basically the ability of the T cells to recognize so many different kind of antigens and basically that is happening at the genetic level only when the T cells are being produced then these T cell receptors they have the ability to bind to different types of antigens similarly this MHC1 this is also having the ability to present different types of antigens so that heterogeneity is not only in T cell receptor it is also present in MHC1 and it is because of inherent randomness in producing this binding sites that we see that no two individuals except twins no two individuals have same complex of MHC proteins and that becomes clinically relevant because because of this different complex of MHC proteins which are present there is rejection of the graft in organ transplantation okay moving on to MHC2 so MHC2 as I told you it is present on antigen presenting cells and why it is present on antigen presenting cells because these cells have the ability to recognize the extracellular antigens so what they do they take up this extracellular antigens the phagocytos this extracellular antigen it is taken up inside the cell and in the cell they are present in the vesicles then this vesicle goes and fuses with the lysosomes okay so extracellular antigen is being degraded in the lysosome intracellular antigen how it was being degraded it was being degraded by the proteosomes here the degradation is by the enzymes present in the lysosomes so within the lysosomes there will be peptide fragments and then they interact with MHC2 in vesicles okay within the vesicles itself they interact and then these vesicles go and fuse on the membrane causing the presentation of the antigen to the T cell receptor so if we see the major differences what is the difference MHC1 is presenting the intracellular antigen and the degradation is occurring in the proteosomes and the binding with MHC1 is occurring in the endoplasmic reticulum here it is extracellular antigen degraded in lysosomes and binding is occurring with MHC2 in vesicles and then there it is fusing with the membrane and presentation is occurring to the T cells now which T cells here the antigen presentation occurs to helper T cells because these helper T cells are CD4 positive CD4 positive and like in MHC1 alpha 3 domain was having the CD8 binding site here beta 2 domain beta 2 domain of the beta chain has CD4 binding site okay so the T cell receptor binds with the antigen and there is a CD4 recognition by means of the binding site on beta 2 domain so these helper T cells are known as MHC2 restricted MHC2 restricted okay and like I said in cytotoxic T cells similarly there will be co-stimulation so there is two signals required so now what will helper T cells do see these are extracellular antigens so what these helper T cells do is they activate various mediators of the immunity so they activate B cells then they also activate macrophages they also activate the cytotoxic T cells as well okay because if there are certain cells which are infected by these antigens then these cytotoxic T cells can go and kill them if the cell is not able to handle these antigens so before ending let us see certain applied aspects of this antigen recognition and antigen presentation first of all see if in the body MHC protein is not present for recognition of any bacterial peptide see every antigen is recognized by a different sequence of amino acids which are present in the antigen binding site so if an individual doesn't have that particular MHC which can identify that particular infection then the person will be susceptible to that infection understanding on the other hand if any person has that particular MHC then it will cause the resistance to that particular infection so that is one second why there are certain people who are sensitive to certain allergens but other people are not sensitive to other allergens that is because if MHC is present for binding antigen from pollen suppose then in that case that person will be susceptible to pollen grains and there will be allergic reaction in that particular person so whether the immune response is occurring or not that depends on whether the binding site for that particular antigen is present or not finally very important is in tumor cells tumor cells basically use this process and evade the cytotoxic lymphocyte response because we are telling that these T lymphocytes are killing the cells which are having these abnormal proteins then why is that the tumor cells grow because they evade this kind of response and activation of the T cells so little bit in detail we will see how that is happening tumor proteins may cause reduced expression of MHC molecules so if there is reduced expression of MHC molecules then the nucleated cells will not be able to present the antigen to T cells and obviously then there will be no lymphocyte activation or it can cause a decreased expression of co-stimulators in the antigen presenting cells so antigen presenting cells here means the nucleated cells because these tumor cells are there so if there is decreased expression of co-stimulators then as we told you that it is basically the signal 2 which is causing the activation of the lymphocytes so if co-stimulators are not there then there will be no activation of the lymphocytes and finally these tumor cells can cause inhibition of response of the T cells this is very important because pharmacological therapy is being developed based on this okay inhibition of response of T cells now what happens that whenever there is activation of the T cells there is natural checkpoints also so that there should not be too much activation so suppose this is a presentation this is MHC right and here there is T cell receptors now on these T cells there are present certain other receptors and one of this is CTLA4 which is basically a inhibitory receptor and there is another receptor as well that is the PD receptor PD1 receptor on T cells so these tumor cells what they do is they basically produce certain proteins and release them such that it causes the binding of these proteins on the CTLA4 and when this happens CTLA4 activation causes the inhibition of the response of the T cells and similarly it can produce ligand that is the PDL okay L is for ligand so increased production of PD ligand it will bind to this receptor and there will be inhibition of T cell activation so that is another mechanism by which tumor cells evade the cytotoxic lymphocyte response so basically they are using this natural checkpoints for their own advantage and preventing the activation of the lymphocytes now pharmacological therapy against this has been developed actually and there is a Nobel Prize also which has been given for the discovery of this mechanism of action so how will the pharmacological therapy act simple just block these receptors okay just to block these receptors by certain drugs such that these receptors are not activated so if these receptors are blocked then the tumor ligands which are being released by the tumor cells will not be able to bind to these receptors and they will not be able to inhibit the cytotoxic lymphocyte response so that was all about antigen presentation and antigen recognition specifically by the T cells thanks for watching the video if you liked it do press the like button share the video with others and don't forget to subscribe to the channel physiology open thank you