Type 1 Hypersensitivity Reactions | Immediate Allergic Reactions

today our topic is hypersensitivity reactions right so hypersensitivity reaction what is really meant by this right as the name implies that probably hyper mean exaggerated hypersensitivity reaction the literal meaning of this is exaggerated immune reactions but you remember all hypersensitivity are not exaggerated the point which you have to remember all hypersensitivity reaction are not exaggerated so this is a misnomer the real concept of hypersensitive sensitivity reaction is any tissue tissue damage in damaging immune tissue damaging immune reaction so any tissue damaging immune reaction in your body should be considered hypersensitivity reaction it may be truly hypersensitive mean it is truly exaggerated response or sometimes even very appropriate immune response may do some damage in your tissue is that right and even very appropriate immune responses may be hypersensitivity reaction so the best way to define what is hypersensitivity reaction hypersensitivity reaction is any immune reaction which damages your tissue this is that right now hypersensitivity reactions are very commonly classified into four types right hypersensitivity reactions are very commonly classified into four type type 1 type 2 type 3 and type 4. the four types of hypersensitivity reaction type 1 type 2 type 3 and type 4 the art of understanding is that you must be able to differentiate every react type from the other types is that right first you have to remember type 1 type 2 and type 3. all of them involve antibodies all of them involve anti-bodies so this is also antibody mediated type 1 is also antibody mediated type 2 is also antibody mediated type 3 is also antibody mediated and type 4 does not involve antibodies Type 4 immune reaction does not involve antibodies it depends only on the cells so that is why it is also called cell mediated cell mediated hypersensitivity reaction hyper sensitivity reaction now the point which you have to understand is and type for cells are involved immune cells are involved but no antibodies involved in first second and third antibodies are always involved and even some immune cells may also be involved so real differences in type 1 and type 2 and type 3 they they do involve antibodies and type 4 does not is that right there is no antibody involved into Type 4 hypersensitivity reaction now because type 1 2 and 3 all of them involved antibodies let's see how they are different from each other as the right will discuss their differences a little bit then we'll go to detail of every type right now in type 1 first of all we talk about antigens antigens in type 1 antigens are usually free antigens free antigens and foreign antigens foreign antigens free and foreign antigens what I mean by this for example pollen grains enter into your respiratory system and start some hypersensitivity reactions if pollen grains are going of course they are free antigens they are not fixed in your tissue they are free antigens and of course they are foreign or for example that some house dust might yours developing hypersensitivity to house dust might material is that right now again that is foreign addition and that is free antigen or you develop a hypersensitive sensitivity reaction to penicillin right so that is foreign and free now antigens and type 1 are always foreign and free right but antibodies in type 1 are antibodies and type 1 are yes are always ige antibody type is ige and this IG is fixed on fixed on mast cells must cells or base of Health mast cells are present in tissues and basophils are present and circulation and very small amount now look what really happens in type 1 hypersensitivity reaction that in type 1 hypersensitivity reaction antigen is free but antibody is bound antibody ige is free in the plasma in very small amount and most of the ige antibody is bound on the mast cells and the basophils so here antibodies fixed and antigenous free now let's come to the type 2 and type 2 reaction what really happens that antigenous always fixed and intrinsic intrinsic to the tissue on which reaction occur on which reaction occurs for example in type 2 antigen may be fixed on the surface of RBC then reaction will occur only on the RBC our antigen may be fixed and intrinsic to glomerular basement membrane then reaction will only occur on the basement membrane now listen how type 1 and type 2 are different in one way and type 1 antigen is always foreign to tissue to which reaction is occurring and type 2 antigen is always for a fixed and intrinsic there are two points to be noted here antigen is fixed on the tissue or in the tissues and it is intrinsic to the tissues for example look if this is an rbce and this is an antigen on the r they say if immune system is going to react against this antigen then this antigen is intrinsic part of this RBC and this antigen is fixed on the RBC or if there is glomerular basement membrane suppose this is membrane and this is an antigen which is the part of glomerular replacement membrane and if immune reaction occur against this antigen again antigen is fixed it is not freely freely circulating antigen and it is intrinsic to the tissue RBC antigen is also fixed on the RBC membrane this antigen is not free into body fluids or it is not free in plasma is that right so the very very important point is worth worth repeating that in type 2 reactions antigen is always fixed and part of the tissue to which reaction is foreign is that right am I clear right now so antigens are intrinsic to the reactive tissue and antigen is fixed an antibody is usually here antibodies usually is what type of antibody is there usually it is IGG or IG M or it is immunoglobulin IGM right General Motors g m type 2 hypersensitivity reaction does not involve ige it involves IGG or it involves IG M right now another thing the effector system listen keep on comparing and type 1 antigen was foreign and type 2 antigenous intrinsic to the tissue to which reaction is occurring this antigen may be original or this antigen may be modified by some drug or it may be modified some microbe but antigen to which reaction is occurring is intrinsic right here antigen is free their antigenous okay and type 1 antibodies always ige and antibody is fixed mainly on the Mast Cell then desophil very little ige is free in the plasma so most of the ige with which the reaction really occur is fixed on the mast cells or basophil now listen here immune complex will form where on the muscle because antibody is sticking to the Mast Cell the bisophil so antigen has to come to the mass cell then this of health so antigen and antibody will react only on the surface of Mars cells and basophil is that right but here because antigen is fixed antibody has to come to the Target cell or Target tissue so an immune complex will form antigen antibody reaction will form only and only on Target tissue now look here do you think here antigen or antibody complexes will be found free in circulation or free into tissue answer is no and type 1 because antibody is fixed even though antigen is free but antibody is not free so when antigen antibody fuse right the fuse on the surface of muscles and basophils so fused antigen antibodies are not found into tissue fluids is that right and type 2 again come the antigens are part of the cell membranes oriented in the part of the particular neurological membrane or Olive membrane or any tissue antigens are fixed and intrinsic even though antibodies are free here but antibody have to go to antigens so antigen antibody reaction will occur in type 2 always on the target tissue surface type 2 antigen antibody reaction will occur always on the target tissue and in type 1 antigen antibody reaction will occur always on Mass cell than vasophils so in type 2 also and type 1 in both cases you will not find freely circulating antigen antibody complexes in body tissues or body fluids or into circulation is that right why hair antibody was fixed and their antigenous phase now we come to the type 3 hypersensitivity reaction and type 3 hypersensitivity reaction what really happens that antigen may be extrinsic exogenous or it may be endogenous in case of type 3 hypersensitivity reaction antigen may be exogenous or it may be endo genus now it means this point will not help us attention plays this point will not help us to differentiate type 3 from 1 and 2 where is the difference let me tell you type 2 differences that in type 3 antigen may be exogenous or endogenous but this is free but this is free antigen is always free it may be endogenous antigen or it may be exogenous antigen but it is free and what about antibody antibody in case of type 3 is IGG or IGM but it is also yes free here antigen is free as well as antibodies free so it means antigen antibody can react into tissue fluids or into circulation and make free immune complexes so it means the Hallmark of this situation is formation of formation of yes formation of free immune complexes and this is the unique point to type 3 with that free immune complexes are not formed in type 2 because anti-gen is fixed and free immune complexes are not formed in type 1 because antibodies first that is why conventionally we call type 3 reactions and immune complex reactions because we can find immune complexes and free form ideally look look ideally this should be called free immune complex disease right but conventionally or traditionally they simply call it immune complexed mediated disorders type let's recap so what again what hypersensitivity reaction it is any immune reaction which damages our tissue it may be hyper response it may not be hyper response it may be a very appropriate response but again any tissue damaging reaction is hypersensitivity reaction hypersensitivity reactions are classified as type 1 2 3 and 4. type 1 2 and 3 they are what antibody mediated and type 4 does not involve antibody it purely depends on immune cells so it is also called self-mediated hypersensitivity reaction now its very important to differentiate between type 1 2 and 3 because Type 4 is too easy to differentiate that any hypersensitivity reaction which does not involve antibody and which involves only the immune cells must be type 4. so how do you differentiate in type 1 2 and 3 the one way to differentiate is in type 1 antigen is always foreign and free foreign end free antigen is always foreign and free like pollen grains are like you can say some food stuff some people develop allergy to egg or some people develop allergy to Seafood some people develop allergy to their wives some people develop allergy to their teachers I don't know so but I'm not concluding last two examples that a psychological hypersensitivity reactions let's come to the immunological hypersensitivity reaction we are indigenous foreign and it is pray is that right when we talk about type 2 hypersensitivity reaction antigenous in part of intrinsic tissue antigen is fixed fixed and part of an intrinsic to the tissue on which reaction is the king antigen is fixed and intrinsic to the tissue to which reaction occur right and in type 3 antigen in type 3 reactions antigen may be exogenous exogenous or it may be endogenous but it is free and even if it is endogenous it is free for exogenous example is a streptococcal antigens entering your body they may be freely circulating in the end they get deposited into gloomarly onephritis or endogenous antigens are free like DNA molecules may be free in the blood in case of SLE systemic lupus respect ulcers and if anti-dna antibodies react with the circulating DNA they make immune complexes is that right examples of type 2 antigens are fixed fixed and intrinsic antigens for example antigens as a part of RBC membrane antigens embedded in the neutrophil membrane antigens present on the platelet membrane antigens present on glomerular basement membrane right but antigens are free not free they are fixed and intrinsic to the tissues here antigens are free now we come to the antibody involved what is that antibody involved hair antibody is always ige always hygiene right and fixed on and fix mainly and mainly effects very little ige is free in the plasma but the antigen antibody reaction occur with the fixed right so we say and ige is the antibody and it is fixed on mass cell then mass cells and circulation right then and type 2 yes it's very important to understand in type 2 antibody is IG or i g n and of course this is even freely freeing the body tissue but remember antibody is free here antigen is fixed so because antigen is fixed on the target tissue so immune complex will always form on the Target tissue right and no we should write especially no free immune complexes immune complexes no free immune complexes in type 2. again in type 1 even though antigen is free but antibody is fixed so antigenetic body reaction will always occur on the Marcel of basophils again there is no free immune complexes no immune no free immune complexes but when we come to the type 3 reactions antigen may be exogenous or endogenous by antigenous free and at the top even the antibodies also free antibody may be IG G or in type 3 reaction it may be IGM but the important point is it is free so as indigenous free and the body is free so free so free immune complexes immune complexes may be found maybe may be found yes and circulation and circulation or three complexes may be found in circulation or tissue fluids if reaction is local type tissue fluids right so this is a very very big difference is that right now the detail of now I will go for every test into detail every type into detail I will go into detail of type 1 then we'll go into detail of type 2 and eventually in the detail of type 3 and 4. right is there any confusion among them so if I say that a foreign antigen coming to your body and you have made ige against that what is this type one and if I say that there is there's a stem cell in my bone marrow and there is a protein on my stem cell an antibody form and react against my stem cell proteins what is this type 2 and if I say that there is some circulating drug in my blood and against the drug I have made antibodies and an antigen antibody complexes form in circulation and deposit into different places and damage what is this type is that right and if I say so virus enter in my body right and or okay if I say fungal Center in my body and against the fungus cell mediated immunity started damaging and no antibodies involved what is this reaction typhoid now I will do randomly without any sequence we have for example some horse Serum is injected in your body horse Serum is injected into of the slump body and horse serum for abdislam body will be self for foreign serum as your own serum or foreign serum hopefully foreign first lesson my question is if I introduce horse serum into your body horse serum will be perceived by your your immune system as self proteins or foreign proteins you are very sure okay maybe horse is not sure anyway if horse serum come into your body and you make antibodies against the horse serum we are just posing you make antibodies against the horse serum proteins and horse serum protein and your antibody make complexes and moving into your circulation and deposit here and there what is this reaction type one two or three proteins they have entered into your body of course by injection is that right and foreign right and I do have made antibodies an antigen antibody complexes are circulating in the blood type 3 right now another example if a fungus come into your body and against the fungus you have made ige and that is loaded on the mast cells what is this reaction they've won excellent and if I say that I give you a drug and that drug goes and bind with the antigens on rbcs drug goes and modify the antigens on purposes drug goes and modifies the antigens on the rpcs and your immune system make antibodies against modified proteins of the rbgs what drug has done drugs fused some of its part with the antigens of your rbcs and rbc's antigens are modified and against this modified anti-gens which are your own intrinsic antigens immune system make antibody and now immune system will attack only RBC is not rest of the body to type 2 so now you really understand it I'm happy now we're going to detail of type 1. now let's take an example of type 1 reaction ah we will Define this reaction later we'll Define type 1 hypersensitivity reaction later let's start with the story to understand it right one of our student can come here Mr Audi will come here no no you don't want okay someone has to come here we'll take another okay Raul is coming you bring a chair here because you have to sit and as a perfect example of type one hypersensitivity reaction right yes good you sit here now I will tell you a story about Mr Rahul how he developed type 1 hypersensitivity reaction right uh he went he passed his usml step one with 99 score 99 score right and he wanted to celebrate with his uh okay he was in his country when the result came Buddha's family so he wanted to give them very good you know party to his mother and father sister and brother not to girlfriend later on privately now what really happens that he takes his family to a very special Garden where there are new flowers right it's spring season and polans are in the yeah he also called many of his friends but not his girlfriend many of other is friends so all his family members and all his friends they are enjoying in their garden and having good food having good time and Poland are going through their noses all of them have noses right so police are going through their noses to the respiratory system now what happens that pollen grains are foreign material when they come into respiratory system let's draw a respiratory system here the respiratory system of one of your friend okay respiratory system of one of your friend now what really happens that this is the pollen when Poland is coming into respiratory system right there are two Fates number one you know respiratory system is having these are special epithelial lining and it has what are these Celia and this cilia are beating upward one thing what may happen to this foreign substance or particle is that this pollen is beaten upward through the mucosillary mechanism there's a mucous lining right pollen is stuck into mucous lining and Cilia are beating it upward so mucociliary clearance will take the pollen towards the larynx so most of his friends May swallow the from the larynx the mucous respiratory mucus along with the pollen right may be thrown from the larynx into esophagus and they will swallow it and throw the pollen wrapped into mucus into your acid full acid full stomach and destroy the pollen this is one way second thing is that if pollen really come very distal Poland come very difficult then ideally this pollen should be it eaten up by a macro fade so this macrophages going to eat of this pollen normally what should happen listen now carefully normally what should happen that macrophage should alveolar macrophages respiratory macrophages should take up the pollen right and let's suppose this is macrophage is that right and here's a macrophage nucleus here is phagosome and what is here here is Poland so these are pollen antigens these are pollen antigens now what really happens that lysosomal enzymes will be released here and in most of your guests what really happens that pollens proteins may be dig degraded up to amino acid pollens fats lipids may be broken down to fatty acids and pollens carbohydrate may be broken down into monosaccharides and all these basic components are recycled in the cell you can say pollen antigens are completely destroyed and if pollen antigens are completely destroyed will there be any immune response answer is no answer is no so what is happening that all of your friends there and your family member whatever pollens go to the respiratory system they destroy the pollen completely and they don't develop any immune reaction towards that pollen but your case is different what is your special case that your immune system has decided to react against the pollen now if we see that how his immune system is going to react against the pollen now this is your personal special venture that your macrophages are different than others macrophages what you really do suppose this is your respiratory macrophage this is your respiratory macrophage here is the pollen let's suppose I make your pollen colorful because it's going to develop a special type of problem for you right pollen has come here now this is pollen and these are pollen antigens what are these these are pollen antigens right and here is macrophage nuclear material now what really happens that even though lysosomes release their contents into this but they break down the pollen antigen only partially they break down the pollen antigens only partially and this is the pollen antigen and unfortunately his HLA genes the genes on chromosome number six there's a chromosome number six of course you must be having one chromosome number six from your mother another should be coming from your father so chromosome 6 has special genes which are called MHC genes or HLA genes these are making Class 2 molecules these these genes are making special type of MHC Class 2 molecule one of the class two molecule react with the pollen react with the pollen antigen now this is the sad thing because if Class 2 reaction Class 2 molecule MHC Class 2 molecule is present in your macrophage which can bind with this pollen it means this pollen antigens will not be further degraded rather these pollen antigens will be presented to the immune system remember in other member other guests who went with you they also had the Poland the difference in you and other people is that other people who went with you did not make such Class 2 which could bind and present the pollen but you are unfortunately genetically programmed to make such type of Class 2 molecule which could bind with the pollen antigen and present to the immune system now as soon as Class 2 molecule bind with the pollen then further Poland antigen degradation will be halted there will be no further degradation of Androgen now this pollen antigen will be expressed on the surface of macrophage along with which molecule M H C Class 2 molecule whenever now we can say this macrophage has taken up the foreign antigen and process the foreign antigen with class 2 molecule and now antigen with the class 2 molecule is ready to be presented to the immune system so this macrophage will rush to the lymph nodes there it will find a special type of T Cell it will find a special type of T Cell right and what really it happens this special T Cell should have TCR TCR what is TCR TCR is T Cell receptor for the antigen what is TCR tcrs T Cell receptor for the antigens so unfortunately in his body he has such type of T cells which are having such antigens which can recognize pollen unfortunately his body has our immune system has such type of T Cell which are having such a receptor which could recognize pollen antigen but most of the people who went with you maybe even if Class 2 molecule bind with the pollen some of them may not have such T Cell which could recognize the pollen antigen do you get it now second thing that once TCR bind with the antigen then second is another molecule here and this molecule is called yes CD four molecule and this 3d4 molecule react with class 2. if pollen antigen is processed with the class 2 molecule within the antigen presenting cell in this case antigen presenting cell is macrophage right antigen presenting cell took the pollen antigen bind with the class 2 present to the appropriate T cells and then it gives some core stimulations also which I will not discuss in detail now but what really happens that this T cell is activated right of course this molecule is CD3 so when TCR and CD4 are stimulated they stimulate which molecule CD 3. this 3D 3 will give message to this lymphocyte nucleus and its nuclear Machinery will be activated and this T cells nuclear Machinery first of all it the first Gene will be stimulated and this Gene will make interleukin 2 then second Gene will be stimulated and that will make the receptor for interleukin 2 second Gene will make receptor for interleukin-2 so this interleukin 2 will react on The receptors on this T cell again let me repeat it that this T Cell as soon as this TCR and CD4 are stimulated via the CD3 pathway it will activate the nucleus and nucleus genes Gene the first Gene which is activated it will produce interleukin-2 so this cell will start circulating interleukin two molecule secondly this cell will start over expressing for receptor for interleukin 2. now as soon as the receptor for interleukin 2 is stimulated the receptor gives signal to the cell and in the cell this Gene is activated this Gene is concerned with mitosis so this teeth this special type of T cells undergo mitosis and when this T Cell undergo mitosis there are millions of such T helper cells are made right which are sensitive to pollen now what happened that such T cells which are resulting or you can say this clonal expansion of this Poland sensitivity cell you're getting it that this unique T Cell which could which had such TCR which could react with Poland antigen this T Cell will undergo Auto proliferation or Colonial expansion what will happen there will be clonal expansion when there will be clonal expansion this T Cell will multiply when these three cells will multiply we say that his circulation is very rich in or in his body has become very rich in this unique subset of T cells once they have enough you know once these T cell have proliferated enough then they activate another group of genes this Gene will produce interleukin for and other Gene will produce interleukin-5 and this reaction that activation of the gene for interleuking four and five this occur into all group so this massive production of interleukin 4 and 5 in this hip body now but unfortunately introducing four production in his body has been extremely excessive there is unduly excessive interleukin force produced in his immune system this was another fault we'll see because this excessive amount of interleukin force must to produce ige is that right and this was another fault that when that you activated interleukin-4 Gene not with slightly increased activity but superly increased activity so when interleuking 4 become extremely high that this helps the cells B cell the plasma cell to produce which antibody IG e now meanwhile some of the pollen antigens may have gone look there is a B cell here now part two of the story this is a B cell in his lung is that right and this B cell have surface receptors these are B cell surface receptors and these are called bcrs BCR mean B cell receptor for the antigen you know there was TCR this is T Cell receptor for the antigen here is B cell receptor for antigen right now actually some of the free pollen antigens some of the free pollen antigens bind with bcrs some of the free pollen antigens right bind with the bcrs B cell receptors now B this B cell which was sleeping ah this B cell become active this B cell has its own genetic program and this this activate the nuclear Machinery of this B cell and what happened look here this Gene is activated and this Gene produces a receptor for interleukin 4 this Gene makes the receptors for yes please interleukin4 these are interleukin for receptor but there may be many B cells there are other B cells also there the other B cells also there but only that B cell which had such PCR which could recognize Poland antigen only those B cells start expressing which receptor interleukin for it means only this B cell will become sensitive to after looking for other by standing B cell will not be sensitive to interleukin4 interleuking 4 as many function one of the function of interleukin 4 is that it act as yes it act as B cell B cell growth factor because interleukin 4 in low and moderate concentration can stimulate the B cells of course only those B cells which are expressing interleukin four receptors and stimulate these B cells and force them to multiply now what happens that these B cells will start multiplying right these B cells will start multiplying you can say pollen sensitive B cells will start multiplying right this is called again clonal expansion of B cells here they have a Poland Colonial expansion of T Cell here there is clonal expansion of B cells when we sell the colonally express expanded then what really happens that all of them start expressing yes all of them start expressing the receptor for interleukin 5. right so what really happens that interleukin 5 will react with them and when introducing 5 will react with them all of them will convert into plasma cells all of them will convert into under the influence of interleukin 5 all of them will convert into yes plasma cells plasma cells are active B cells what are plasma cells these are active B cells which have been appropriately stimulated and they have a card they are oval cells with a nucleus which is cartwheel shape or nucleus which is clock face shaped and these active B cells or plasma cells have eccentric nucleus because they are having a very prominent Golgi operators and this Golgi operators is so that these cells are planning to synthesize and export some proteins now what really happens these all B cells have been working under the influence of interleukin 5 interleukin 5 convert the B cell into plasma cell but in the presence of very high amount of interleukin4 these beats these plasma cells start secreting the antibodies antipolar antibodies what antibodies anti-pollen antibodies and these antipolar antibodies are belonging to the class which immunoglobulin class E class so we say that all these right so what are these NT up to now there is no type 1 reaction it is only preparation of the reaction antipolon ige immunoglobulance now there's a big change in his body that in his body with the help of T cell that is why because these T Cell helped the B cell to convert into plasma cell and produce antibodies so thus the such T cells are called t helper 2. these are T helper two cells we'll talk later about the helper one when we talk about Type 4 hypersensitivity reaction so what are T helper two cells these are those cells which can help the B cell and to convert into plasma cells is that right now there's a very special change in Rahul body which is not in his friend's change and parents or brothers and sisters right what is the change the changes he is making anti-pollen ige and because this ige has special receptors present on the Mast Cell let's suppose this is a mast cell this is mast cells mast cells have unique type of receptors every muscle they have unique type of receptors as well as basophil they have also similar receptors and these receptors love to bind which antibody ige so as ige is being produced by these plasma cell ige will bind with the mass cells now his mass cells and even basophils will be loaded by ige but yet type 1 hypersensitivity reaction has not occurred but he is a changed person now he has no he has no clinical problem up to now but he is a changed person why before going to that party and garden he was not having anti-pollan ige and he was not having any anti-polar ige loaded Mast Cell then base of Health but now he has a change and it this change take how much time it takes about 10 to 15 days so when he went to the party and the new flowers new pollens right and unfortunately he processed the Poland and presented to the T cells and T cells were capable of converting the B cell into plasma cell which produce anti-pollen ige and anti-pollen ige is now loaded on the mass cells and the basophils whole this process take 10 to 15 days so after 10 to 15 days his body is altered his immune system is no more normal his immune system has is such type of muscle and bisophils that which are ready to react with the pollen if next TriMet reappears is that right and now you see he is playing with his girlfriend to go to the same Garden in the late evening times late hours is that right and it's about let's suppose one month now after one month of the first party now you are planning a second romantic type of party only with you and with your girlfriend and you're planning to go to the same Garden in front near the same flowers and probably going to inhale the same Poland and unfortunately you are not going to have romance because your body has already anti-poland IG loaded on the mast cells and basophils and there can be severe immunological reaction we'll talk about this after the break all right now we'll see we have talked about how these are formed now we sum up what we have discussed already and then continue the story what happens to Raul when he goes with his girlfriend there right we have already discussed that what was there that Poland green came pollen grain was taken up by the macrophage and then Poland with the class 2 molecule presented to the T helper cells right and T helper cells were activated they released interleukin 4 and convert the B cell and activate the B cells into Colonial expansion is that right many B cells and then they release interleukin 5 and these B cell converted into plasma cells and these plasma cell produced IG e and this ige was binding with the must felt this is what we have already discussed so this part of the story we are here now we'll discuss this into detail that what are mass cells and what are the factors which can stimulate the mass cells from where they come where they are present is that right and then we'll see in particular case overall what really happens so let's suppose here the mast cells foreign now must sell the corrective tissue cells but they are derived from the bone marrow and similar cells similar cells are present in circulation also and these similar cells are called basophils these are called basophils but they are present in circulation very small amounts so mast cells and basic filled are functionally very very similar but the very big difference is basophils are moving in the circulation and mass cells are present in our connective tissue right but basophils and mass cells both are derived from the bone marrow now ma where the mass cells are present Mars sell the present in all the connective tissue of the body but mass cells are specially concentrated in perivascular connective tissue Mast Cellar specially concentrated right around the perivascular connective tissue it means whenever mast cells will be activated vessels will react strongly mast cells are specially concentrated in perivascular connective tissue secondly mass cells are present in all that that connective tissue which is under the internal and external lining especially in sub-epithelial connective tissue mass cells are specially concentrated around the blood vessels and in Sub sub epithelial connective tissue subepithelial connective tissue mean all the connective tissue under the mucosal lining and all the connective tissue Under the Skin So Much cells are specially concentrated under the skin they are specially concentrated Under the Skin Mars cells are specially concentrated under all this mucosal lining laryngeal and pharyngeal right even Mast Cell the well concentrated all the mucosal under the mucosal lining of git right and master even comes well concentrated under the mucosal lining of urogenital system and of course now what you learn about mast cells number one muscle is a connective tissue cell from where it is derived it is derived from derived from bone marrow and we were talking about mast cell that they derived from the bone marrow right and they're well distributed in the body connective tissue they're specially concentrated around the connective tissue around the blood vessels that is why in type 1 hypersensitivity reaction the strong vascular responses then type Mass cell the well concentrated around the internal lining that is mucosal lining of git mucosal lining of respiratory system mucosal lining or urogenital system so these type 1 hypersensitive reactions involve mucosal Linings as well then mast cells are very well concentrated and in the skin connective tissue just under the skin so that is why that type 1 hypersensitivity reactions also involve skin reactions is that right secondly that what are the factors which stimulate the mast cells what are the factors which stimulate the mast cells right so that muscle release their product the factors which stimulate the mast cell number one is your IG E I told you IG is present on the mass cells IG is present of the mass cells and when allergen substance bind with the ige right when allergen substance bind with the ige especially if these are two ige binding on the mass cell the threeige especially those allergens which are multivalent the allergens which can react with multiple ige and cross link the IG look this is an allergen right it can it could react with multiple iges and cross-length IGS this is one of the very strong stimulant to the Mast Cell so strong Mast Cell can be stimulated by the cross linking of cross linking of ige by the allergy allergens like pollens number two mast cells can be stimulated by c3a and c4a and c5a right these substances can also stimulate mast cells Mass cell receptor for complement components right C5 AC3 and c4a especially c3a and c5a their receptors are present on the mass cells and when during inflammation C3 and c5a are produced they can activate the mast cells then mass cells can be stimulated by drugs some drugs can irritate the mast cells like codeine or morphine morphine right drugs like codeine or morphine they can stimulate the mast cells then mast cells can also be stimulated by the Venoms venoms or for example snake bite or you know one of the Venom is melaton melaton the snake bite or Venom from bee sting from the Beast tank right or from the ant sting so these mass cells can be stimulated by these substances but specially if you have made ige against these substances is that right so but Venom of the snake melaton can directly stimulate mast cells then mast cells are so sensitive that even physical agents can stimulate them like cold can stimulate or heat energy can stimulate mast cells or physical trauma physical trauma can stimulate must cells is the right even strong sunlight can stimulate Mass strong sunlight can stimulate mast cells so what we'll learn about the muscle the very very sensitive they can be stimulated by so many different factors and once the mast cells are stimulated they produce strong inflammatory reactions they release the product which act as chemical mediators of inflammation is that right so after having said few words about the Mast Cell situation back to Mr roll then what really happens to Raul now we have discussed one month back he went to the Garden pollen grains came to his body Poland antigens was taken up by the macrophages presented to the immune system and T cells activated the B cells and B cell converted to plasma cell which produce ige and those antipolar ige were loaded on his now after one month of the previous experience now he is sensitized due to First exposure he is sensitized against Poland right because in his body they are mastled and basophil loaded with ige against the Poland now he is going with his girlfriend to the same Garden in late evening hours we'll see what happened there right actually as soon as Poland will start going in the already pre-sensitized cells so this time as soon as Poland antigens will touch the ige on the mass cells Mast Cell will have explosive response right they will start producing lot of chemical mediator let's see what will happen in his lungs the reaction is going on within his lungs and what is happening within his lungs okay lung is too small this is his bronchial tree and this bronchial trees now loaded with the mast cells these are small mast cells and these Mass cellular yes these muscles are having anti-poland ige antibodies on them as soon as pollens will start coming in as soon as pollens will start coming in his respiratory system this mast cells will be stimulated now we see what really happened with this mast cell activity but before we talk about that let's look at the bronchial histology because mast cells present in the bronchial system will degranulate and they will produce a pathology there so let's look at the I will draw here these are the epithelial cells in the bronchial what is this mucosa mucosal lining right and here are some glands which glands circulatory glands right and here are some blood vessels and the mucosa and submucosa especially in submucosa and then here are what are these bronchial smooth muscles bronchial smooth muscled now this was the bronchial section and this is what I draw from now where the mass cells are present let's suppose Marshall the present here these are the mast cells around the blood vessels and under the mucosal line in near the glands these are the mast cells and these mass cells in his respiratory systems are loaded with antipolon IG e and here is the pollen grain whether it's pollen antigens these are special antigens right foreign these antigens will be presented to the mass cells and muscle will be activated I'll bring one mask fell here to show what exactly happened with the mast cell this is muscle membrane right here are the receptor which receptor receptor for an FC portion of ige these were anti-poland these are anti-pollen IG e these were anti-poland ige and these are the receptors mast cell receptors for antipolar IGA now here are the antigenetic domain of pollen grain and these this is the allergen or antigen this is polyvalent antigen which react with multiple what is this IG is on the surface of the mass cells and these are now cross-length what what has happened with them this is a pollen is a pollen grain very very happy it is Valentine right now this is the Poland antigen and these are multivalent antigenic point which cross length the ige as soon as ige is cross length multiple reaction below number one intracellular intracytoplasmic signals will come and within the cells there are granules there are granules present in the mast cells and there will be signals go into cytoplasm cytosol and these granules will come to the surface and they will start releasing their products this granules will start releasing their products is that right these are preformed products the products which will be released from here are histamine histamine will be released from there for muscle granules right and along with the histamine there will be proteases proteases proteolytic enzymes these enzymes can break down the proteins along with that some preformed neutrophil chemotectic factors and acinophil chemotactic Factor so neutrophils will love to come there now mast cell is calling mast cell is activated and it is calling neutrophil as well as it is giving a special call for the sinophils neutrophil chemotectic factor and the sign of elect chemotactic Factor meanwhile these proteases will do two things number one they will do further tissue damage tissue damage and when tissues damage more inflammatory mediators will be produced inflammatory mediators will be produced number two proteases will convert some complement like C3 or C5 and these proteases will convert and c3a will be generated and C5 a will be generated c3a and c5a they do have receptors on the Mast Cell these are the receptors for what C3 a receptor R C5 a receptors when C3 and c5a are produced more and more in the site of activity add reaction site of course reaction site is bronchial wall the wall of the histamine within the bronchial wall they are stimulated so this is the reaction site so they have locally lot of c3sc 5A is produced and when they see three A and C 5A will act on the mass cells right they will further stimulate the Mass cell so it means it's a local amplification Loop that once Mars cell is activated it releases proteases proteases break down the produce active complement factors some of the active complement Factor do have receptor on the mass cells and mass cells are stimulated further is there clear secondly there is histamine now histamine has many functions number one histamine is vasodilator Vaso dilator so these blood vessels look at these blood vessels they will be dilated these blood vessels will be dilated number two and under the direction of histamine endothelial cells will shrink when endothelial cells will shrink that will produce increased permeability for me ability of micro area so when this will become more permeable so naturally this vessels will become as they're dilated and more permeable so edema formation will develop in sub mucosa what will happen that edema formation will develop fluid will start coming out of mucosal vessels from the local vessels and edema formation will start right so there's increase permeability thirdly they are strongly spasmogenic spasmo genic now look at it that spasmogenic there are histamine receptors which are present on what these smooth muscles so struming will act on this smooth muscle and they will become now you see blood flow in this area is increasing blood flow in this area is increasing there is edema formation there this is the right at the top now it means submucosa will swell up it will swell up so Lumen will be reduced when you submucosa will swell up with edema and right Lumen will reduce at the top histamine is histamine is led to the bronchial smooth muscle contraction that further reduces the Lumen now it's a difficult time coming for him can he breathe well he cannot right so at the top the strumming can stimulate glandular secretions glandular secretions so even in the Lumen these glandular secretions are becoming more this glands are producing more secretions right and then glands are producing more secretion it means there's luminal obstruction this mucosal and some mucosal swelling and this bronchoconstriction all these factors are reducing the airway caliber and this type of reaction is occurring into multiple sites within the bronchial tray right this type of reaction is occurring into multiple sites within the bronchial tree this reaction which is occurring so fast and rapidly this is called initial phase reaction what is this initial phase reaction and these preformed substances which are released by The these preformed substances which are released by the granules these substances as a group are called primary mediators that is histamine in the primary mediator proteins is the primary mediators and neutrophil and xenophilic chemotectic factors these are called what these are the primary mediators so we can say that as a group all these should be called yes all these should be called primary mediators of type 1 hypersensitivity reaction primary mediators what are primary mediators primary mediators are preformed chemical substances right present within the mast cells and they can be immediately released is that right secondly the second reaction will occur that is to the nucleus let's suppose this is a nucleus and in the nucleus this genetic material and what really happens second pathway signal pathway is going to the nucleus and the nucleus is stimulated naturally it will go to it will produce messenger RNA nuclear activation will activate the different genes it means Mass cell genomic program is now activated and this will take some delay right and then it will produce messenger RNA messenger RNA of course ribosomes and production of what peptides and those peptides will be thrown into Golgi apparatus you know endoplasmic reticulum and Golgi operators and eventually this cell will start releasing certain small soluble protein which act as messenger in between the cells now when nuclear Machinery of the mast cell is activated right nuclear Machinery direct the synthesis of small soluble proteins which are secreted by the cell these small soluble proteins are going to act as signaling molecule in between multiple cells as a group these small molecules are called cyto kinds so what are cytokines cytokines are group of group of small yes group of small soluble proteins which are secreted by many cells in the body including the mast cells and these cytokines right they act as signaling molecule or communication system or messenger system in between the different cells right now there are many types of cytokines which are produced by this but these cytokines are not preformed because these cytokines are not preformed so these are not called primary mediators this group of cytokines are called secondary mediators and secondly these cytokines are like tumor necrotic factor which is released by mast cell interleukin-1 interleukin the many many interleukins which are released interleukin 3 interleukin 4 enter you can five interleukin sex so it's not difficult to remember just omit the interleukin to so interleuking one two three four five six then granulocyte monocyte Colony stimulating Factor right granulocyte monocyte Colony stimulating factor and macrophage inflammatory peptide macrophage inflammatory peptide you're not supposed to remember all of them but at least the minimum you have to remember is until you can three specially and you should have a special interest in interleukin 5. you know why these are the special molecules which call the acinophils these are the special molecules which we'll call the eosinophils because the xenophiles should come at the site now there were already xenophilic chemotectic factor that was preformed so that was part of primary mediators right but many interleukins are produced sorry cytokine the produces secondary mediators right and out of these secondary mediator interleukin three and five especially you can say chemotactic further your signal feather so that acinophils should start coming to this area these are the xenophils so neutrophil will be coming there xenophiles will be coming there later on we'll find neutrophil sinophils the lymphocytes natural color cell all these infirmative cells will come at the site and these this process of cellular activity that cells inflammatory cell accumulate at the rejection site that this takes a half hour to two hours and then this continues for half hour to 24 hour then this inflammatory cell accumulation and their strong damaging reaction may continue for many days that is called late phase so why there is a late phase reaction in type 1 hypersensitivity that is due to accumulation of inflammatory cells at the reaction site and early phases in type 1 hypersensitivity reaction early phase or initial phase or immediate phases due to vascular events due to vast major dilatation increased permeability due to vascular events plus spasmogenic event again remember in type 1 hypersensitivity reaction there are vasogenic vasogenic products produced and spasmogenic product produce this vasogenic and spasmogenic product they produce initial phase of the problem and eventually lot of cytokines are produced locally and many other demotectic factors are produced which call lot of infirmative cells there so lot of you can say the signal fails accumulate there asinophils especially attracted by the most strongest chemotactic agent for xenophilus interleukin5 so interleukin 3 and 5 are produced by mast cell and you should not forget your old friend you know T helper 2 that could also produce interleukin 5 that can also produce interleukin-3 so interleukin 3 and 5 will be produced by T helper two as well as they will be produced by mast cells and both of them will be calling your son of Health at the same time under the influence of all these cytokines even epithelial cell will start producing a substance called EOTech Texan you Texan now look at this this is the queen of the type 1 hypersensitive reaction what is the screen this is a synonym for the bilobe nucleus the xenophiles have buy load nucleus right the bilobed nucleus and this is three and five you can say they have glasses number three and five they are attracted by interleukin-3 and they're also attracted by interleukin 5 and they have a nucleus the sinophil has a nucleus like glasses spectacles and here is interleukin3 here's interleukin 5 right so interleuking three and five attract the acinophil at the site of reaction and this is three and five are produced introducing three and interleukin 5 they are produced by number one t helper two two plus they are also produced by mast cells so together they call this enough Health but we should not forget even epithelial cell produce EO Texan a product which also stimulate the cinophil arrival so it means as time will pass by xenophils will start coming over there due to a cytokines and chemotactin produced by the helper cells from the mast cells and even from the epithelial cells even from the epithelial cells is that right now one thing which is very important is to understand one more aspect that we have learned that one signaling pathway will lead to cytoplasmic stimulation and release of preformed primary mediators second another signaling Pathways that stimulated the nuclear Machinery that has led to the release of cytokine the secondary mediators is that right then another you can say signaling pathway is stimulating the what is this cell membrane it was going to cytosol it was first pathway was going to the cytosol second signaling pathway was going to the nucleus third pathway stimulating the mast cell membrane and within the muscle membrane there's a very special type of what enzyme and this enzyme is called phospholipids A2 within the mast cell membrane there is a special type of enzyme called phospholipids A2 and this phospholipids A2 when it is stimulated this will break down the phospholipid in the membrane right this will break down the phospholipids in the membrane and those phospholipids will be broken down into under the direction of phospholipids A2 phospholipids will be broken down into arachidonic acid they have broken down into arachidonic acid so as soon as muscle the stimulated lot of arachidonic acid produced within the muscle membranes due to activation of phospholipids A2 is that clear now this arachidonic acid will be acted upon by more enzymes which are present within the Marcel membrane and those enzyme can take this rachidonic acid through two pathways those enzymes can take the arachnic acid into two Pathways uh some of the arctonic acid will go into lipo oxygenase pathway lipo oxygenase pathway and other enzyme will take it along the cyclone that will take it along the cyclo oxygenase pathway cyclo oxygenase pathway now what really happens that along the Lipo oxygenase pathway there will be production of different type of leukotrienes what are substances produced that arachidonic acid will progressively broke down into final product and the final products will be B4 liquor train C4 leuko train D4 and liquidrine E4 now if you have to remember one thing this liquid train B4 is a strong chemotactic agent for neutrophil this is uh leukotriene B4 the strong chemotactic agent for neutral Falls so it means many many neutrophils will come into this area now you see what is happening here very bit tragedy there is a lot of accumulation of blood vessels are dilating micro circulation is becoming more permeable edema formation is going on glandular tissue is stimulated and more secretions are coming right secretions are obstructing the Lumen and submucosal swelling is also reducing the Lumen at the top many substances are acting as plasmogenic and producing now you know what is the most powerful plasmogenic in the world known what are the most powerful spasmogenic known please tell me what is the most potent Vaso active and spasmogenic agent what is the most powerful vasogenic and spasmogenic substance I mean the substance which can strongly act on vascular system and strong edema is produced and substance which can strongly act on smooth muscles and produce very powerful construction that substances thousands of the time more potent than histamine I think good doctors should know that even I've written it on the board this substance is legal train C4 D4 E4 as a group they are the most potent vasogenic and spasmogenic agents known up to now what does it mean Raul is going into big trouble so powerful spasmogenica produce forget about histamine more things are now coming already histamine was producing spasmogenicity now at the top slow previously these were called slow reactant substance of NFL axis right but anyway a C4 D4 E4 they produce now very powerful bronchoconstriction and spasticity at the top these three substances are very strong stimulant to endothelial cells endothelial cells shrink intern endothelial gaps are appearing and too much edema is forming you understand what is happening that already histamine was working against you is that right and now you could read that also working against you meanwhile cytokines are accumulating many many cells is that right so this is repeatedly what is happening the waves and waves of chemical mediators are coming producing Vaso dilatation increased permeability more more you can say edema right stimulation to what is this glandular secretions spasmogenic activity all this is deteriorating his respiratory system function right by this time he's feeling cough he's finding difficult to breathe and at many points what is happening that bronchial trees slightly and when air passes through slightly narrow areas some whistling effect occur and he may start producing some whistling and some dyspnea that that whistling is called visas and his girlfriend is not a medical student she may think start looking around maybe he is trying to whistle some other girls he's not and she's not understanding he's in trouble and he is trying to be Champion behaving nothing is happening to me but very soon things are going out of his control right so what is happening to Mr all that he is coughing with that he has developed difficulty in breathing unpleasant awareness of breathing process right we call it dyspnea and with that because bronchial spasticity at multiple area make the bronchial tree as small narrow narrowings and multiple narrowing mean that as multiple whistles have been planted in his Airways and he start developing whistling sounds especially during expiration is that okay now story is not yet over meanwhile what happened that through the cycle oxygenase pathway prostaglandin pathway is continuing and the most important important prostaglandins which are produced over there are yes D2 E2 and F2 but most abundant prosta glandine which is produced by the mast cell is pgd2 this prostaglandin is now abundantly accumulating being produced by the muscle membrane product and accumulating here this is strong vasodilator this is very strong as you can say micro permeability increaser but more importantly it's very strong stimulant for the glands so this glands start secreting more and more products so glandular secretion increase visual literary factors there right and this further aggravate the situation is that right now let's see what is happening meanwhile meanwhile you should not forget another product is coming into uh game and that is platelet activating Factor this is also derived from the membrane lipid platelet activating factor is also derived from the membrane rapid and its mechanism of action to remember what it is doing is most easy it does everything which is what all other together are doing it can produce weather dilatism it can produce increased permeability it can produce more histamine relays it can stimulate the muscle it can but most important thing even though that platelet activating Factor by name you can see it can aggregate the platelet it can act on the mast cell and release more histamine it is very strong bronchospastic agent now look at it the poor round the bronchospasticity by histamine bronchospasticity by the leucotrans bronchospasticity by the platelet activating Factor then vessel dilatation further by an increased permeability by platelet activating Factor but the most important factor is that platelet activity agent act as very strong chemotectic agent chemotactic agent it means they will also call lot of inflammatory cell it means when more cytokines production and platelet activating Factor production will activate the late phase because late phase of the type 1 hypersensitivity reaction is uh you can say has a Hallmark of accumulation of lot of inflammatory cell at the site of reaction that is why for early phase these are the wizard alert reactions as spasmogenic action and increased permeability action the early phase of type 1 hypersensitivity is due to visual validation visual validation increase permeability a demand flare you can say increase blood flow increase permeability more edema formation and early phase there is bronchospasticity that is why early phase is mainly strumming dependent or gluco trains dependent is that right late phases specially by accumulation on inflammatory cells inflammatory cell why they accumulate infinitely select tubulate because in the beginning neutrophilic chemotactic factor is realized xenophilic chemotactic factor is released then lot of cytokines are released they are calling lot of inflammatory cells you remember interleukin three and five specially called a cinefeld neutrophils are there macrophages are coming there lymphocytes are also coming there do you think it's all good news for its tissue because all these inflammatory cells will come and produce their dangerous product and further damage the situation and these inflammatory cells will damage the what is this epithelial cells epithelial cell injury will be there that's the right and even epithelial cells are so stupid they don't sit innocently epithelial cells start releasing themselves chemical mediators epithelial cells start releasing themselves chemical mediator like your Toxin and like interleukin35 can also be produced by epithelial cells it means epithelial cell also enhance the whole situation is that right now under all these circumstances what will happen that there will be severe tissue damage at time will pass by especially don't take acinophils lightly the xenophils can produce two very dangerous products one is a basic yes swindonfield number one they produce catanic proteins the xenophil produce positively charged proteins we call them xenophil cationic protein other thing the produces major basic what is that major basic protein this major basic protein and acinophilic acinophilic catanic proteins these two are very very dangerous because they can damage epithelial cells and many other cellular components around the or near the or within the reaction site does that right so how many players are in this game so many is that right again listen let's start thinking of the players the first player was remember first player was your antigen presenting cell that was your first player second player was the helper sales to which indigen was presented third player was B cell converting into plasma cell and producing the Real Player oh sorry Master the Real Player because they bounce the ige so four number player is the most important player that was a must sell because martial brain released a lot of chemical mediators five number player was who was coming there the sin of Health a synonym for the inflammatory Zone and then six number neutrophone seven number macrophages all infirmities cells are coming and please don't forget your friend who was so stupid to them do themselves further damage and these are epithelial cells right in a lot of chemical mediators are produced in this game uh these chemical mediators which are preformed like these three things these are primary mediators but cytokines a secondary in the same way leukotriened and prostaglandins are secondary mediators because this denomers their new synthesis of the product platelet activating factor is secondary mediator so muscle produce chemical primary mediators as well as secondary mediators and Mast Cell along with other inflammatory cell and epithelial cell produce so much chemical mediators of inflammation that there is increased visual validation this increase permeability this edema formation there is uh you can say swelling of the submucosal swelling of the semicol area reduction in the Lumen at the top increase secretary activity by the respiratory glands so that will lead to further occlusion of the Lumen and many of them like platelet activating Factor like your nicotine C four D for E4 like histamine all of them can produce really very powerful spasmogenic action so he will develop of this problem and very soon what will happen that his girlfriend will realize he is under trouble he's not whistling to other girls maybe he's in a very serious problem because whistles are not coming from the mouth they are coming from the chest is it right now what what she will do leave you and run away or she will take you to hospital you are not sure somehow you have to be sure right so what do you think Yara most of the girls friends they do what under these circumstances yeah they call 9-1-1 that take the culprit to hospital okay so she she's an intelligent girl she knows what girls will do they will call 9-1-1 but don't hand over the boy to those people tell them to that he should go to the emergency right so they will take him to the image and say then you know what they will do that hopefully if they are having oxygen they will put there right if they are having bronchodilators like salvita mall they will nebulize to him and of course with that they must give steroids and taste means uh substances are usually not given but in anaphylactic shock they are given right and especially they will give steroids the steroids are very useful to prevent the late stage it depends on the inflammatory cell activity that's the right because if you give the stereo to the patient then naturally accumulation of acinophils and neutrophils and lymphocytes and accumulation of monocytes macrophage all these inflammatory cells accumulation will be prevented or suppressed is that right okay like prednisolones like a solo Cardiff I mean of course if he's under sphere trouble they will give intravenously a parental steroids right now few more important points related with the type 1 hypersensitivity reaction already we have taken example overall that how he developed type 1 hypersensitivity reaction to allergic pollen grains and that was actually leading to what problem that was leading to asthma that clinical pathological condition is asthma now listen asthma now the important point which you have to remember that different people develop different types of hypersensitivity reactions some hypersensitivity reactions are localized localized hypersensitivity reaction localized type 1 hypersensitivity reaction and some people develop generalized generalized type one hypersensitivity hypersensitivity reactions and some unfortunate people develop both types now examples of localized hypersensitivity reaction where for example there are so many you can say environmental allergens right for example just dust or the pollen grains or there are the Ender of the as you can say from birth feather or some people develop from something from the horse right there's so many factors or allergic substances depends on against what substance a particular patient is making ige is that right now there's so many types let's talk about that if uh you are having let's suppose anti-allergen ige on the Mars cells present in the conjunctival mucosa then you will develop allergic conjunctivitis allergic whitest some people uh they have ige loaded mast cells in the nasal mucosa against the allergens and if they are inhaling the allergen they will develop allergic yes rhinitis allergic rhinitis right then there are some people they develop you know swelling of the lips and nasal swelling of the lips with that there's swelling in the larynx and parents and all that swelling in response to some allergic substance that is called allergic Indio NGO edema that is called angioedema right then there's another condition which is called hay fever have you heard of hay fever this is another allergic situation in which person develop allergic allergy or type 1 hypersensitivity reaction in the conjunctiva type 1 hypersensitivity reaction in nasal mucosa like sneezing and type 1 hypersensitive reaction in the larynx and pharynx also so then someone has Type 1 reaction only in conjunctivitis he develop red eyes is that right and itching in the eyes someone develop allergic rhinitis itching in the nose right and with you know I in the lecture I keep on touching my nose have you noted actually I have allergic rhinitis and when I'm not uh taking the drugs I keep on somehow adjusting my nose appropriately probably this energy in the nose which keep undermining from itching there thank God I have allergy in the nose I move only my nose right then you have allergic conjunctivitis so maybe you are too much sensitive about your eyes then injured him is really bad because the sphere swelling of the lips I mean uh the fleshy margins around the oral cavity right lips and swelling of the you can say something oral mucosa or most importantly in angioedema there may be life-threatening swelling of laryngeal mucosa right in that laryngeal mucosam may lead to life-threatening situation in hay fever someone has developed type 1 allergen in which he develops you can say red eyes he develops sneezing and he patient develops also a sore throat type situation and with that laryngeal swelling laryngeal infringal allergic reaction and if the reaction goes more deeper that may become allergic asthma allergic asthma then type 1 hypersensitivity reaction may be related with the skin you know many people who are allergic to Common environmental substances when they come across the legend they may develop on the skin they are you know uh red patches or you can say hives right or patient may develop arithmetics rashes on the skin right or some reactions like wheel and flare flare and wheel right or some aortic area so all these are the allergic reactions type on hypersensitive reaction in the skin then some people develop in the git many examples of the food allergy is that right there's someone who take a special type of food and if all the JD mucosa is loaded with anti-allergen ige on the mast cells the mast cells in the G80 will you know dig around late and produce the product patient will develop abdominal cramps and diarrhea may be right in the same way you must be knowing someone who has allergic to egg so actually you can develop allergy to anything depending upon you have capacity to make ige against that particular environmental substance or not and right so there can be skin allergies respiratory allergies there can be JD allergies right these are all examples of localized allergy these are all examples of localized allergic reaction opposite to that some people develop unfortunately uh systemic energy type 1 hypersensitivity reaction the classical example I can give you someone who developed ige against the penicillin right and he has developed sensitivity to penicillin so what really happens that if you give test tools of pencil in the patient usually develops a localized allergic reaction like wheel and flare but if unfortunately without the test tools you have given a good dose of unfortunately a good heavy dose of penciling in the intravenous system not only heavy even small dose can do the unfortunate thing that all the mast cells around the cardiovascular system will degranulate and when all the blood vessels will dilate and you can see all the micro circulation will start losing the fluid so patient will go into shock and this shock is called yes anaphylactic shock Anna phylactic shock anaphylactic shock is an example of systemic hypersensitivity reaction and in these patient of course uh when you have given parental leave the allergen right not only all the blood vessels dilate and increase permeability and blood pressure drops Under the Skin also all the muscles be granulate there are so many Mars cells and those are under the skin degenerated that will produce what type of problem yes patient will develop erotic areas and red rashes is that right so this person will develop the rashes you will develop falling blood pressure and naturally even respiratory system Mast Cell will degromulate this person will develop difficulty in yes difficulty in breathing so and if git muscles deconlate this person it will also develop abdominal cramps right abdominal pain visceral pain in the abdomen or abdominal cramp right so this type of multi-systemic an uh ige mediated Mast Cell dependent reaction is can occur with multiple allergens which are given intravenously as I told you it can occur with injection of the drugs it can occur with injections of hormones if you reject some peptide hormone to someone and a person has already pre-sensitized against that particular peptide hormone and person has made ige against that hormone as soon as you inject the hormone person will go into anaphylactic shock right in the same way this can occur with enzymes injections of enzymes injections of hormone or injections of foreign proteins like anti-sera or injections of drugs or polysaccharides right so this may put produce itching on the screen and hives skin erythema respiratory distress and abdominal pain and eventually cardiovascular collapse and if you don't do some heroic Measures patient will die Within NR right so the management of that patient you will learn in shock another important thing is that there is a special type of desensitization therapy you know what is desensitization therapy for type 1 hypersensitivity actually what we do that if we give the we give extremely small amount of allergen apparently if patient can tolerate you extremely small allergen and if you keep on giving repeatedly small amount of allergen patients start making IGG against the allergen patient was previously making IG e and if you repeatedly challenge the immune system patient may start making IGG so if patient circulation become very rich in IGG this is the immune headquarter and previously it was through this door it was making IG e which is loaded on the muscle and here it is making IG so repeated square of the immune system and very small amount of allergens the slightly progressively increasing doses may make IG J the next time when a legend comes it may bind with IG and IGG will block the allergen approach towards ige so these are blocking IGG antibodies which are produced right this is called desensitization therapy what is decentralization therapy in type 1 hypersensitive patient with your progressively increasing small doses of allergens so that patient may develop and T allergen IGG not IG and if patient successfully develops anti-allergen IGG with repeated injections levels of IGG are boosted you know secondary immune response and if IGG level does significantly boosted the next time when a legend will come uh IGG will bind with the allergen and block the approach of allergen to the ige and patient will be prevented from severe anaphylactic reaction or type 1 hypersensitivity reaction right then and a few more points that how do you diagnose type 1 hypersensitivity reaction one of the test is skin prick test skin trick test that Under the Skin you inject extremely small amount of allergen and a wheel and flare is formed there it means localized mast cells are decrangulating right it means person is allergic to that particular substance secondly skin prick test right or some people call it scratch test that a specific allergens are injected just under the skin and will look for formation of wheel and flare reaction right if this reaction is there then it means that there is type 1 hypersensitivity against this particular allergen as VLAN flare reaction is due to localized mast cells degranulation and other chemical mediator production then another test is a rast test rust Stanford for radio yes radio alargo Radio logo should I write rast stand for radio immuno servant test now I will not go into detail of this test detail will study in other lectures of Immunology where we study the antigen antibody Laboratory test only I'll mention that rasps test is used to detect a specific this test is used to detect specific ige against a particular allergen for example if you want to see you have antipolon ige or not or you are having IG against a particular drug or not so the test which is done is rust test right another simple test which is non-specific is of course in most of the patients who have type 1 hypersensitivity reactions uh they are having higher level of IG in the blood and they are having a higher number of sinophils in the blood now another thing which I want to mention is the concept of atopy have you heard of the concept the word of atopy or atopic tendency the topic is a familial tendency write it down atopy is a familial tendency to make ige more frequently it will be the familial tendency to make ige more familial more frequently against the common environmental substances ige more frequently against the common environmental substances to which most of the population is Unearthed or to which most of the population is non-reactive right so in some families it's like this that father is allergic to let's Okay this is multiple family members may be allergic to different things maybe sun is allergic to soap daughter is allergic to toothpaste components or makeup substances right maybe mother is allergic to nylon and your father is allergic to mother right so when situation like this occur last for example ponder over there think over that right that when multiple family members may be developing allergic to multiple different sub environmental substances to which most of the people are a nerd we say this atopic tendency in that family right so and secondly recently they have started looking for that is what is the genetic component in utopic tendency we believe that chromosome number five there are some genes which are related with development of allergy actually at chromosome 5 especially that cluster of genes which is related with synthesis of Lord of lot of interleukin cytokinesis chromosome number five there's a special Locus at for at which there are multiple genes to synthesize the interleukins probably in someone if interleukin 4 is produced more evil per day has a higher chance to develop type 1 hypersensitivity reaction then some other people have a local has suspecting that some genes add chromosome number six near the HLA cluster they are related with that type 1 hypersensitivity because of course it's very understandable if you have inherited such type of MHC or HLA genes which are making such Class 2 molecule which are processing and presenting more commonly environmental substances if you have higher chances to develop type 1 hypersensitivity reaction are you understanding or actually repeated that if you are you have inherited such type of MHC genes which make such type of Class 2 molecule which can bind and present common environmental substances you will have a tendency to develop allergy so to develop type 1 hypersensitive reaction these people have a high tendency to have such type of Class 2 molecule which can bind with the common substances and present to the immune system secondly these people have higher

Channel: Dr. Najeeb Lectures

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Keywords: medical lecture, dr najeeb, hypersensitivity, immune complex disease, immunology, cell mediated hypersensitivity, hypersensitivity reactions, allergy, types of hypersensitivity reactions, immune system, electromagnetic hypersensitivity, ige antibodies, hygiene, allergies, type 1 hypersensitivity reactions, igg or igm antibodies, igm, igg, eczema, igg antibody, innate immune system, usmle, dr najeeb lectures, iga, hypersensitivity reaction, immediate allergic, immediate allergic reaction

Id: F7men17BG0g

Length: 108min 14sec (6494 seconds)

Published: Sat Nov 26 2022