Mast Cells in Allergic Asthma | Anaphylactic Shock

now we will discuss the connective tissue cells  in proper detail one of the very important cell is   mast cells so we'll discuss mast cells into detail  why i'm discussing mast cells into detail because   they are playing a role in many physiological and  pathological processes you remember there was one   monkey which was very very sensitive whenever  tissue is damaged jumps around and produce lot   of products that monkeys called mast cells mass  cells is present in all the connective tissue of   the body except in central nervous system that  brain and the spinal cord does not have mass   cells and connective tissue in order all the  rest of the body is very rich in mast cells   right now about the mass cells first of all let me  tell you how they work i will draw one muscle here   let's suppose okay we start a story  that will help you to understand how   the mast cells work mast cell play a very  very important role in allergic reactions   especially in type 1 hypersensitivity  reaction you have heard of allergic asthma   you heard of that allergic asthma right so  the major role is played by the mast cells   or have you heard of anaphylactic shock someone  was given pencilling and person was sensitive to   penicillin and died within few minutes again the  major player was mast cells right so in many types   of allergic reactions uh mass cells are the major  players so we can take one example that how mass   cells work right we can take this boy because  he's sitting very near his name is raheel and we   see that he's going to develop allergic asthma and  we call it asthma or asthma asthma okay whatever   you call it right in my country they call it  asthma i think you call something else anyway   you understand in asthma what happened that person  who has allergic asthma when he is exposed to the   allergens he developed difficulty in breathing  because there is obstruction to the air flow   and bronchial tree constrict now what really  happens how a mass cell producer travels let's   start with a very basic concept let's suppose here  is mr rahil and he goes to visit a special garden   with his uh girlfriend okay he has a girlfriend  so with his girlfriend he goes to a garden   and it's a spring season and a lot of pollen  grains in the air he's in a very flowery mood   right and he's inhaling pollen grains right  now most of us when we inhale the pollen grains   our macrophages destroy the pollen grains and  don't react to the pollen grains but he is the   unfortunate person who is going to develop  an allergic asthma to the pollen grains how   exactly it happened let me draw you have it  i don't know right so now you'll know what is   really going on your lungs right let's suppose  this is his lung and these are his airways   you know airways bronchi break down  into smaller bronchial airways right now   what i do that let's suppose he has inhaled the  pollen grains and pool and grains are coming down   these are the pollen grains now when pollen grains  are going down of course they are not going only   in his respiratory system pollen grains are also  going to his girlfriend respiratory system as well   normally what happen a healthy person when pollen  grains or pollens are going in their lungs here   they are having special type of macrophages what  are these macrophages there are special type of   macrophages in respiratory system these are called  alveolar macrophages and bronchial macrophages you   know what these macrophages are doing here they're  all the time patrolling in the respiratory lining   and whenever some pollen grain comes or some  bacteria come they will that phagocytose that   and digest that away this is the normal duty of  macrophages which are present on the lining of the   respiratory system is that right now what  happens let's suppose here is this macrophage   and here is the pollen grain  suppose pollen grain now   this is the pollen grain normally what  happened that when pollen grains go to your   respiratory system macrophage will phagocytose  it after phagocytosing this is a phagosome   macrophage will have special type of granules  in which they have destructive enzymes   these granules are called lysosomes macrophages  normally have lysosomes what macrophage   macrophages do they catch the pollen  grain or bacteria and make a phagosome   and then empty these very dangerous  type of enzymes into phagosome   so when these enzymes from lysosomes go into  phagosome they digest away the bacteria or by the   pollen grains let's suppose if this macrophages  in some other person who is not going to develop   allergy it will work in a different way the pollen  has come in here is pollen here is lysosome both   of them fuse and take the destructive enzyme here  destructive enzyme completely destroy pollen grain   for example proteins of proteins or pollen  grains will break down into amino acid   carbohydrates off pollen grain will break down to  monosaccharides so pollen materials are destroyed   and most of you but person who is going to  develop allergy something unfortunate will happen   what is that unfortunate if you are going  to develop allergy against the pollen   then what happened because you have taken  the pollen antigens right you don't break   it completely you break it only partially  you only break it partially and after that   macrophage unfortunately fuse a special type of  protein molecule with this and present this pollen   antigen with a special protein on their surface  this is very sad thing normally what should happen   colon should be taken by macrophage and completely  destroyed but the person who is going to develop   allergic reaction person who is going to develop  allergic reaction what is the unfortunate thing   that that person will take the antigen of the  pollen bind it with special type of molecules   and express it on the surface it means  this antigen is not completely destroyed   unfortunately it is very proudly presented to  the immune system that look what we have caught   and we have taken this antigen with the special  molecule this is called class 2 molecules   mhc class 2 molecule so with class 2  molecule this antigen is presented to the   other lymphocyte what happens some lymphocyte  will have a receptor to recognize that   this is a protein on the lymphocyte  which can bind with the antigen   it's supposed to protein component of the  pollen so this protein is called receptor of t   cell when receptor of t cell will bind with what  pollen antigen and other molecule from this cell   from this lymphocyte will confirm that it is the  pollen properly presented with class 2 or not   again listen carefully this is lymphocyte what  is this macrophage macrophage called the antigen   process the antigen with class 2  molecule presented to the lymphocyte   lymphocyte recognize the antigen with its receptor  and recognize that class 2 with special molecule   right now if lymphocyte recognized this offer  of macrophage lymphocyte become active this is t   helper cell i will not go into detail this tlp  cell will produce some product and those product   will stimulate b lymphocyte they will stimulate  what is the cell b lymphocyte t cell helping   the b cell and b cell will become active and they  convert into a cell like this this cell is called   plasma cell this is called plasma cell  please remember plasma cell is not in plasma   it has nothing to do with plasma plasma cell  is a b cell which is activated what is plasma   cell it is an active active b lymphocyte  so what what macrophage has done macrophage   offered the antigen to the t cell t cell activated  the b cell and converted them into plasma cell   plasma cells start making antibodies what plasma  cells start doing they start making anti pollen   antibodies what are these antibodies anti pollen  antibodies now what has happened to raheel that he is now chained he is a person who  is having anti-poland antibodies in his   body he is different now most of other people  right now this anti-poland antibodies which   are produced by the plasma cells they will go  into blood and into local lymph nodes and these   antibodies love to stick to the surface of mass  cells this is now point to understand that once   this body is having anti-pollen antibodies  if here is a mast cell this is a mast cell   mass cell has receptors special protein receptors  on its surface mass cells have receptors on its   surface and on these receptors what can bind  anti-propolant antibodies they only bind   the receptors on the mast cells only  bind antibodies belonging to ige class so this antibody which is made against the pollen  this belongs to which class of antibodies ige   class you will study that in higher classes so  what happens that raheel has a problem now that   he has stupid type of macrophages which did not  destroy the pollen their other process the pollen   and present it to the tlp cell which activated  these cells converted them into plasma cell   and made anti-pollen antibodies of ige class  now anti-pollen antibodies will bind to his   muscle now mast cells are loaded  with anti-pollen ige but up to now   there is no allergic reaction up to now there  is no problem it was his first exposure to that   pollen it was his first lifetime first exposure  to that pollen all this process taking the pollen   presenting antigen to t cells and  t cells stimulating the b cell   and plasma cell and antibody formation and  then loading the mast cell take about two weeks   it whole process take about two weeks after two  weeks he is in a very very dangerous situation why   because in his lungs under the epithelium  of bronchial system let's suppose i make a very large bronchial these are what  cells suppose epithelial cells under it   here are the connective tissue and  mast cells what are these cells   mast cells these mast cells are loaded with  anti pollen ige is that right these vast   cells are like loaded guns and when they will  trigger when next time again colon will come   because next time when again pollen antigen  comes it these cells are having anti-pollen   ige and pollen will bind here now look here  here is pollen antigen with vine here and here   and polar antigens will cross link ige on the  surface of mast cell and this will activate   the antibodies and when active antibodies tail  are activated an antibody bind with the pollen   antibodies are activated they activate  receptors receptors give signal to the cell   receptors these receptors give signals signals  are at sea level they activate the cell membrane   they activate the cytosol and they activate the  nucleus i see how muscles are going to produce   troubles in his life that when allergic  substance came again he was a person who   was having mass cell loaded with the anti-colon  ig is as soon as allergic substance came within   few minutes it activates the mast cell and this  receptor gives signal to the membranes they give   signal to the cytoplasm they give signal to the  nucleus and after these signals what will happen   in the cell membrane there is an enzyme  called phospholipase a2 this enzyme is   activated you know what it will do it will  break down the lipids of its own cell membrane   imagine a woman who is very angry and  irritated she keep on pulling her own hair   start throwing it away mass shall behave like that  when it is irritated activated it break down its   own lipids from its own membrane and throw away  the pieces of its lipids so what will happen   if membrane is stimulated  membrane enzymes are stimulated   they break down the lipids in the membrane and  those lipids break down into two types of product   prostaglandins and leukotrienes have you  heard of them prostaglandins are coming   from the cell membrane leukotrienes  are also coming from cell membranes   so what will happen that in this area lot of  prostaglandins are released and leukotrienes are   released now these are connective tissue  cells which are activated from their membranes   prostaglandin leukotrienes are released what  this prostaglandins will do prostaglandins will   dilate the blood vessels blood  vessels in the this area will open up   blood flow will be less or more more let me now  draw a section of bronchial system i open up room let's suppose this is the airway air should  be here right here are his epithelial   cells mucosa isn't it bronchial mucosa   under it he has some connective tissue  in which there are what are these yeah blood vessels right here are some bronchial  what are these glands they can produce secretions am i clear you see how the real troubles  start due to activity of mass cells   these are smooth muscles around  it bronchial smooth muscle and this is the whole bronchial system you know it's a section  here is your nasty mast cell when this muscle is activated it is  releasing prostaglandin rains now what   happens prostaglandin open the blood vessel so  blood flow in this area will become less or more   more when blood flow is more fluid in this area  will become more and tissue will swell up when   this tissue will swell up it will swell  inward so airflow will become more or less   yeah so number one mucosal edema what is happening  mucosal edema this is problem number one problem   number two these are the leukotrienes leukotrienes  act on endothelial cells and shrink them   you know these are endothelial cells like this  when leukotrienes work on them they become like   shrunken they shrink and there are gaps made so  more fluid coming out of vessel tissue will more   swallow number one blood vessels open number  two the cells which are making the lining of   capillaries those cells shrink and  gaps develop and fluid will come   out more swelling of all this tissue is that right  then meanwhile another trouble will start from the   what is this granule in the  mast cell these are pre-formed   chemical substances in this these are called  primary mediators of allergy this as soon as   cytosol is stimulated these products also  come out what are these products histamine   have you heard of it there are axinophile  chemotactic factor neutrophil chemotactic   factor histamine is released then some substances  are released which will attract the asynophels   some substances are released which will attract  the neutrophils it means this is a monkey   which is producing some attractive substances  so that asinophylls jump into tissue   so that neutrophils jump into tissue it  is calling more monkeys into this area   you know blood is passing through this area  it was having white blood cells mast cell is   here it has produced the product here which will  attract the eoxino filled out and neutrophil out   it's a good news bad news bad news because  xenophobe will come and damage the tissue   neutrophil will come also damage that tissue  these are not decent monkeys when they come   out into tissue they start fighting and produce  dangerous substances is that right then histamine   this is histamine you know what it is  doing it will dilate the artery further   plus histamine will shrink these cells further all  this is good for him or bad for him bad for him   is that right at the top histamine has a  receptor on these bronchial smooth muscles   the bronchial smooth muscle will constrict when  all of them will construct it will become narrow   so what is happening the dangerous product  form very moody type of monkey mast cell it   is stimulated when allergic substance bind  with the ige on the mast cell ige activate   membrane membrane produce prostaglandin in the  end glucose trains prostaglandin produce increased   blood flow and increase permeability plus  prostaglandins also produce bronchoconstriction   constricted leukotrienes also increase  permeability by shrinking the cell   plus leukotrienes also constrict these cells  prostaglandins stimulate the gland to produce   more secretions now look at it so sad more  secretions coming here lumen is blocking   all tissue getting swelling lumen is reducing  this smooth muscle contracting lumen is further   reducing airways becoming narrow how  many things are opening the blood vessels   histamine is opening the increasing blood flow  as well as prostaglandin increasing blood flow   how many think shrinking these cells endothelial  cells and increase the permeability prostaglandin   and histamines then how many cells things which  are stimulating what is this bronchial smooth   muscle prostaglandins constrict them histamine  constrict them leukotrienes also construct them   it's a good news a bad news for him it's bad  news then gland also start working more so   more secretions here number one more edema  and swelling here more constriction here   right and still mast cell is not   satisfied so after a little more time this nuclear  machine will become active and nuclear machinery   will make messenger rna which will translate  into proteins and new proteins will come out here   interleukin 1 and tumor necrosis factor they will  also increase the inflammatory processes here   at the top from these granules destructive  proteins will come out they are called proteases   what are these called proteases they will destroy  some tissue here so what is happening in his lung   you know it's all monkey business right that  cells are irritated and they produce the product   from the membrane prostaglandin leukotrienes they  produce the product which are already stored in   granules histamine acenophilic hemotectic factor  neutrophilic chemotactic factor and proteases   because they are already preformed they are  already preformed these are called primary   mediators what are these called primary mediators  meanwhile membrane products are coming as well as   from nucleus nuclear activation orders the cell  to produce more dangerous proteins interleukin 1   and tumor negative factors because these  are synthesized later on so these two   are called secondary mediators again mass cell  produce primary mediators and also produce   secondary mediators what are primary mediators  primary mediators are those substances which are   already present in the mast cell before activation  these are ready-made pre-formed if someone come to   your home and you offer the cake which you did  not eat yourself it is a primary presentation   and then you cook something on offer what is that  secondary presentation mast cell is also like this   it has pre-formed materials primary mediators and  it can synthesize new things and release these are   secondary mediator all primary and secondary  mediators which are produced by the mast cell   in the bronchial system they produce swelling  of the mucosa they produce increased glandular   secretion and they produce bronchoconstriction so  its bronchial airways will become wide or narrow   narrow so can he breathe well so he will find  difficulty in breathing so we say he has dyspnea   difficulty in breathing with that his airways will  become little bit narrow so they star behave like   small vessels you know whistle for example this  is a pipe and if you make a little narrow at one   point it may start whistling because when  it is narrow air will pass through become   turbulent and may approach the sound of speed of  sound so now normally when he is breathing there   is no whistling sound but because many many  areas in his lungs mass cells are activated   and bronchial constrictions occur in multiple  area as if nature has produced or mass shelter   produce many many vessels in his airways and you  you will hear whistling sounds from his chest   that is called wheezing that is called vision so  this was one example that how important are mass   cells in their function and how do they burn  now let me tell you another example where are   mass cells specially concentrated in your body  listen mast cells are specially concentrated   under all epithelia you know under the  epithelia there's connective tissue   so all the connective tissue which is just under  the epithelium is very rich in mass cells plus   all the blood vessels small blood vessels outside  the blood vessels must sell the well concentrated   now let me tell you a more dangerous example what  happens to mast cell imagine if i'm having allergy   to penicillin if i'm allergic to penicillin and  against the pencilling i've made ige if i have   made ige antibody against the penciling then my  all the masked cells in my body are loaded with anti-pencilling ige again listen unfortunately  i'm a person who is allergic to penciling   why i am allergy to allergic to pencilling because  unfortunately i have made ige antibodies against   panceline now this ige antibodies  which are made against the pencilling   they will load all my mass cells in the body   is that right now one day i go to hospital and  there's a young doctor there very enthusiastic and he doesn't know he want to give  me pencilling but does not check the   allergy allergic reaction he directly  give me intravenous pencilling what will happen penciling will spread all over  my body and it will go to every mast cell and   mass cells are loaded with anti-pencillin ige  all my muscles become active all over the body   and they start releasing membrane products  they start releasing the product from   are the granules muscle granule they  start releasing product from the nuclei   now you see what will happen  all my clinical problem will be   according to the tissue in which mass cells  are activated now in this classical example   you have injected an antigen or pencilling into  my blood so it will go all over the body penciling   will spread all my body so all mass cells are  activated now see what will happen number one   all the mast cells under the skin will release the  histamine and their product so skin will swell up   you are getting it i will develop  swellings and redness in the skin   we call it rashes i will develop multiple  rashes due to allergy to pencilling   this is not a big deal the real real problem is  those mast cells which are around my blood vessels   they will produce lot of histamine all my  blood vessels in the body will dilate and   you know what will happen let me tell you this  is my heart and this is my circulatory system   how does the pump which is moving the blood  how much is the capacity of circulatory system   anyone what is the capacity of circulatory  system five liter and what is the volume of blood   five liter it means in a normal person capacity of  circulatory system is five liter and volume field   is five liter it means circulating system is full  is that right so when heart pump in this direction   of course something come back clear and it keep on  circulating now you imagine mass cells are fired   these are the mast cells they produce histamine  all my blood vessels dilate my blood is still five   liter but capacity becomes supposed to later  so blood will settle into the will it go back   so heart will not get the blood and its cardiac  output will drop and my blood pressure will   drop and i will go into shock circulatory shock  it's so simple mass cells are so dangerous because   all the blood vessels are having lot of these  nasty monkeys around them what are these monkeys   mast cells they're very irritable monkeys and  when you gave me pencilling touch these mast cells   where on ige loaded on the mast cells all the  mast cells around my blood vessels release their   product like histamine and prostaglandins and  others these products dilate my blood vessels   blood vessels increase their capacity when they  increase the capacity volume is now normal but   capacity is too much this difference between  the volume and capacity drops the pressure and   i go into circulatory shock while i'm going to  circulate shock and my skin has developed rashes   mass cells in my lungs will also degranulate  and what will happen breathing difficulties   now i'm a man after the injection i develop  pressures my blood pressure is going down   i find it difficult to breathe and i develop  abdominal cramps why the git mucosa lining there   are a lot of mast cells they also fire and you  know git motility become disturbed and i develop   pain in abdomen what is happening before death  what are my problems just before that difficulty   in breathing rashes on the skin abdominal pain and  then blood pressure goes down and then i pass away   is that right this is called anaphylactic shock  anaphylactic shock one teaching you this thing in   detail because these are clinically relevant and  important it's better not to irritate mass health   but the question is that why nature nature put  the mast cells there nature is a master creator   there must be some good thing yes there is nature  has put mast cell not for allergic reactions   not for allergic reaction nature has put these  monkeys that whenever you damage the tissue   muscle produce product open up the nearby  vessels call the neutrophil and xenophiles   right so that whatever is damaging the tissue for  example bacteria they should be eaten up actually   mass cells are there with all good intentions then  whenever tissue is damaged they are very sensitive   i just give you example mast cell can be  stimulated when ig is activated but mast cell   can be stimulated by any type of injury i told  you mast cell can be stimulated by thermal injury   by mechanical injury by microbiological injury  by chemical injury any type of injury to the   tissue will activate mast cells usually it  is a good thing because whenever you for   example some bacteria enter in my skin  bacteria damaging local muscle will be   activated local blood flow should increase more  white blood cells should come there and muscle   produce chemotactic factor the white blood cell  come into tissue and eat of the bacteria normally   they are good but sometimes unfortunately when  we make ige antibody against common substances   then mass cell becomes loaded with ige and then  they react against the allergic substance that   is a problem for us have you heard some people  have allergic rhinitis or allergic conjunctivitis okay some people you know for example one person  goes to the garden and he develop red eyes another   friend goes to the garden he develops red nose  another goes and he develops allergic asthma   all of them have problems with the mast cell  which are loaded with anti pollen ige the only   difference is the first person has a mast cell  loaded with ige in conjunctiva second person has   mass cell loaded with ig in the nasal mucosa third  person has mast cell loaded with the ige in the   bronchial tray what does it mean it means that  if mass cells are irritated in conjunction you   will develop allergic injectivities if  mass cells are activated in the nasal   mucosa and pharyngeal mucosa you will develop  allergic rhinitis that is also called hay fever   and if you have mass cell loaded with ig in  the bronchial tray you will develop asthma   and if you have mass cells loaded with ige all  over the body and then you give allergic substance   into the blood person will develop anaphylactic  shock another classical example of anaphylactic   shock is by insect bite have you heard of it that  some people but simple insect bites simply die   why yeah because simple be strange or some other  for example we also get by a string by the b   but maybe we get little bit problem and then  things become okay but some unfortunate people   take the venom venom of the b string  process in the macrophage proudly present to   t helper cell and they activate the b cell and  person has ige against the b string b venom now   this person when the next time beautiful bee will  visit and sting his mast cell in the body will be   activated and if the if these mass cells are  activated under the skin he will develop only   rashes but if they are activated all over the  body he will develop enough electric shock yeah if you have to develop  enough electric shock then an   allergic substance should go into general  circulation all over the body you have a older it's not as question yeah that's  very interesting question she says that   as peop children grow they grow  out of asthma most of the time   the reason being they say that bronchial system  become less reactive to the product of mast cells   for example in childhood the more receptors of  brown for more receptors for leukotriene on the   smooth muscle as you grow up receptors become  less so you are less reactive to the products   so you grow out of asthma is that it  does not mean that as you grow pollen   disappear from the world it simply means your  own tissue has become less reactive thank god yeah there are many ways to manage these  allergies we'll discuss in senior classes for sure

Channel: Dr. Najeeb Lectures

Views: 64,683

Keywords: mast cells histology, immune function of mast cells, allergic asthma, anaphylactic shock, dr najeeb lectures immunology, dr najeeb lectures, usmle step 1, ninja nerd, osmosis, connectivetissue, mast cell immune reaction, pollen allergy, pollen allergy symptoms, type 1 hypersensitivity, mast cell activation, histamine, anaphylaxis, ige antibody, mast cells, connective tissue, histology, immune system, asthma, asthma attack, asthma treatment, asthma symptoms, mcas

Id: r0kGd16F3pI

Length: 36min 17sec (2177 seconds)

Published: Sat Jun 11 2022