hey guys it's mitochosis perfectionist where medicine makes perfect sense let's continue the physiology playlist and today it's time to talk about the types of hypersensitivity reactions you have type 1 type 2 type 3 and guess what type 4. and this classification is based on what medical says based on the time mainly type 1 is the fastest type 4 is the slowest this is my physiology playlist please watch these videos in order in the last video we talked about the complement system with the three pathways high percentage type 1 type 2 type 3 type 4 type 1 immediate but type 4 is delayed okay about type 2 cytotoxic look at this type 2 is cy2 toxic and type 3 you have 3 antibodies what do you mean by free i mean the antibodies are floating in the plasma they are floating in your blood they are not bound to cells they are not situ like type one also you can describe type three by three words serum immune complexes hypersensitivity which one is the fastest type 1 which one is the slowest type 4. can you describe type 1 in few words or immediate anaphylactic ige mast cells they rupture pew they degranulate pu releasing histamine and histamine can give you the symptoms of an anaphylactic shock how about type 2 cy2 toxic what do you mean i mean i have antibodies okay these antibodies are bound to antigens okay and this happens on the surface of the cell the cell is the cy2 that's why type 2 is site 2 toxic okay how about type 3 3 is free you have antigens and antibody complexes same as two yeah but with one difference the big difference is this happens in the blood and after this since they are hanging around in the blood the antigen antibody complex can end up being deposited in the blood causing vasculitis in your joints causing arthritis in your kidney causing nephritis etc etc etc in type 1 type 2 type 3 we talked about antibodies like ige like the antibody that is cytotoxic like the antibody that's freely floating in the blood but type 4 has nothing to do with antibodies type 4 has nothing to do with the hemorral immune system type 4 is about t lymphocytes cell mediated immunity no antibodies heck no the t lymphocytes are super sophisticated they communicate with each other via cytokines which include the interleukins which is the internet of the leukocytes this is also the story of making a granuloma and this takes time here is a quick overview of the four types of hypersensitivity type 1 immediate okay within minutes all right hey moral immunity which means i'll say antibodies yes such as ige immediate immortal pre-formed antibodies remember ige is ew what do you mean by ew allergy anaphylaxis add to be asthma using ew beasting ew how about type 2 type 2 is cy2 toxic okay we have an antigen antibody complex were on the surface of the cell and these antibodies could inhibit the target most of the time or they could stimulate the target in one case only that's why some crazy textbooks define this specific type as type 5 hypersensitivity but this is a very bizarre classification that only lasted for five minutes and then they went back to classifying hypersensitivity as four types can they inhibit the target sure they can cause inflammation and cell dysfunction inflammation is seen in anti-glomerular basement membrane antibody disease also known as good pasture syndrome rheumatic fever hyper acute transplant rejection this is how your body rejects organs or they can cause cell dysfunction such as myasthenia gravis and pemphigus vulgaris my muscles are in trouble my skin is toast they stimulate the target organ only in one case which is the case of grave disease i have antibodies against the receptor okay what kind of receptor this is the receptor waiting for the tsh so it's called the csh receptor okay but these antibodies will come and stimulate the target have you ever heard of antibodies that stimulate the target no antibodies are weapons of destruction now this is an exception these are antibodies that stimulate the target leading to what well it says if tsh is binding to its receptor oh so a similar effect yeah what does tsh do it tells the thyroid gland to secrete tons of thyroid hormone so graves disease in a sense is a type 2 hypersensitivity reaction okay how about type three type three is also antigen antibody complex in a different location floating freely in the plasma okay this is the cause of serum sickness which is a diffuse and acute reaction or the arthas reaction it's not diffuse it's very localized in one spot on your skin and it's not that acute orthos is subacute serum sickness is generalized arthas is localized serum sickness is acute arthas is subacute and subcutaneous love it subacute subcutaneous type 3 is also the tragic story of the nasty immune mediated vasculitis when these antigen antibody get deposited into the wall of the vessel this is vasculitis they can also get stuck into your kidney this is called immune complex mediated nephritis or into your joints immune complex arthritis this is what happens in lupus this is what happens in rheumatoid arthritis and gazillion other diseases how about type 4 type 4 is the most delayed 3 days or about 72 hours or slightly less slightly more this is cell mediated i'm not gonna send antibodies to destroy no i myself i'm gonna go and kill that bacteria face to face i'm gonna have a strong word with this tuberculosis face to face sell to sell cell mediated or cellular immunity if i can kill the stupid invader i will destroy it how will he destroy it well we are t lymphocytes we have t cy2 toxic cells we kill okay but if i can't kill it well at least i can surround it in a granuloma this granuloma can have caseous necrosis such as the caseiatin granuloma of tuberculosis histoplasmosis blastomycosis coccidioidemicosis or it could be non-casiating basically any other granuloma is going to be non-caseating a famous example is sarcoidosis how to make a granuloma is a story that we'll talk about soon but basically cd4 t lymphocytes will secrete interferon gamma which will stimulate the macrophages to make the granuloma we're done with the overview now let's get into specifics here's type 1 hypersensitivity reaction with the first exposure and antigen enters into my body could be dust pollen etc now it's in my body who's gonna present it the antigen presenting cell is gonna take that antigen process it and present it to whom to your lymphocytes so that the lymphocytes can stop being so naive and grow the fringe toast up when they grow up they become helper cells helper cells okay are you talking about t helper one no t helper one is for type four hypersensitivity i'm talking about the helper two t helper two the one that helps the neighbor yeah and who's your neighbor the medium for side how would you help them i will help them develop from a naive b lymphocyte into a grown-up mature beaten for sight from a lymphocyte that can only make igm and igd to a mature b lymphocyte that can give you all kinds of antibodies igm iga igg ige igd i did this by the means of interleukin 4 especially to make ige so analogon 4 comes from the th2 to stimulate the b lymphocytes to become mature beneficial which secretes ige okay i also secrete analookin 5 which stimulates eosinophils but this will happen more with the second exposure so tell me about the second exposure second exposure to the same stinking antigen okay we call this re-exposure which causes cross-linking of two ige molecules on the surface of the mast cell the mast cell is full of histamine waiting to explode this cross linking of the two antibodies by the same antigen is the straw that broke the camel's back causing mast cell degranulation pew releasing all kinds of mediators such as histamine serotonin eosinophilic chemotactic factor since it's called chemotactic it's going to attract taxi from movement the eosinophils by the means of chemicals what does histamine do bronchoconstriction vasodilation increase capillary permeability which causes exudate and welcome to the land of acute inflammation what does serotonin do bronchoconstriction vasodilation and increased capillary permeability welcome to the land of acute inflammation oh by the way these are pre-formed amines the histamine was already made and ready and loaded inside the mast cell we did not make it de novo the histamine was already there inside the mast cell which was already there just ready to explode waiting for the trigger number three is the aesinophilic chemotactic factor which is going to recruit the eosinophils now these universals came to play to do what to secrete histamines why to clean up this mess two metabolize histamine into degradation products think of this as a kind of a negative feedback thing okay they also secrete aerial sulfatease which also metabolizes histamine and leukotrienes so far you know the story of the first exposure to the antigen and the early phase of the second exposure the story of the histamine serotonin and asynophilic chemotactic factor but let me add another aspect the late phase of the second exposure to the same freaking antigen what's going to happen here the release of prostaglandins leukotrienes and platelet-activating factors to the early phase was histamine serotonin asynophytic chemotactic factor the late phases prostaglandin leukotrienes and platelet-activating factors what do prostaglandins do bronchoconstriction and increased mucous secretion what do leukotrienes do bronchoconstriction vasodilation what do platelet activating factors do um they activate the platelet oh that makes sense these mediators will prolong the inflammation initiated by the early phase and this happens by recruiting neutrophils eosinophils and monocytes unlike the early phase where these mediators were pre-formed and ready to explode the late phase mediators are made on demand de novo from scratch new stuff these were already there before we saw the anton for the second time they just happened to come out of the closet however these were not already there these are made on demand and that's why the late phase is late a classic example of type 1 hypersensitivity is the extrinsic allergic asthma and we have discussed this in detail in my pulmonology playlist these videos are on youtube the notes are on my website next we have type 2 hypersensitivity reaction what's the key word cy2 toxic what do you mean antigen antibody complex on the surface of the cell okay an antigen and an antibody they make a complex where is the complex on the surface of your cell membrane and then what's going to happen there is a story with a complement and there is another story with no compliment if there is a compliment i have two sub stories for you igm or igg these are the only two antibodies that can fix the complement what do you mean boy fix the compliment fix it in place and activate it to end up with the mac which will attack watch my last video please this antigen antibody complex triggered the classical complement pathway which ends up with membrane attack complex the mark will attack causes all kinds of destruction and lysis and breakdown etc hashtag ci2 toxic or i can stimulate macrophages to phagocytose quick reminder the complement is called complement because it complements the function of the antibodies the complement also produces proteins necessary for inflammation and obstenization oh it actually makes sense they are coordinated the second story where we have no compliment we have two substories here as well adcc and antibodies against cell surface receptor what the flip is adccc antibody dependent cell mediated cytotoxicity beautiful i can have ige or igg ige can recruit eosinophils as was the case with type 1 hypersensitivity reaction this is the story of eu allergy asthma b sting anaphylaxis parasites etc e eo eosinophils or the igg activating and recruiting neutrophils and monocytes whether we're talking here or here the end result is the release of inflammatory mediators causing cell lysis psi too toxic or it could be antibodies against cell surface receptors what do you mean i mean a receptor on your own cell okay and the end result could be stimulation of the target organ as in the case of graves disease hyperthyroidism or it could be inhibition of the target organ as in the case of myasthenia gravis which we have discussed in my muscle physiology series it is the norm for antibodies to inhibit the target but when you stimulate the target this is unusual that's why in the past it was known by some doofuses as type 5 hypersensitivity reaction but no more because the pathogenesis is the exact same as type 2. next we have type 3 hypersensitivity reaction if you remember my videos on rheumatoid arthritis i've told you about the story we have a rheumatoid factor what's that it's igm antibody against the fc portion of igg okay this is an antibody against an antibody isn't that crazy yeah in this case the igm is acting as the antibody the igg is acting as if it's an antigen but this is your own antigen that's why in rheumatoid you are destroying your own body not the body of a foreigner antigen antibody complex are floating freely in the circulation when it's free it's type three these are not bound to cell surface and the end result is deposition into tissues if they get deposited into the vessel wall they cause vasculitis into joints they cause immune complex mediated arthritis immune complex mediated nephritis stop wondering why do we have skin involvement in cases of rheumatoid lupus scleroderma etc it's here baby moreover this antigen antibody complex that's floating freely in the circulation can activate the classical complement pathway and giving you the famous c5a which is famous for chemotaxis which means neutrophils are coming causing all kinds of inflammation do you remember fibrinoid necrosis in pathology yeah this is the position of antigen antibody complexes into vessel walls that's why you see fibrinoid necrosis with rheumatoid with lupus with scleroderma etc tell me more about type 3 antigen antibody complex in the circulation could be a generalized reaction all over the body or it could be a localized reaction such as king arthur king arthur is very local the generalized type has two subtypes the first one it's not your doctor's fault that's the story of the autoimmune disease such as rheumatoid or lupus or it could be your doctor's fault hashtag serum sickness reaction you had a disease your doctor injected you with another serum from another body could be the body of a human a horse or recently made in the lab why did my doctor inject me with these antibodies because you had a disease these antibodies were supposed to help your immune system okay they can help your immune system but everything has a trade-off like what you developed your own antibodies against the foreign antibodies ending with an antigen antibody complex that's floating freely in the circulation ends up depositing into tissues activating the complements hypocomplementemia and you get all kinds of generalized symptoms contrast this generalized serum sickness reaction caused by the anti-serum with the localized arthas reaction serum sickness reaction is generalized arthas is localized serum sickness reaction is acute arthas is sub acute and subcutaneous someone injected me with something subcutaneously or intradermally what happened the problem is i was already pre-synthetized oh you were sensitized to the same antigen before yes and now with this exposure i developed a small localized sub-acute subcutaneous or intradermal lesion this is the arthas reaction hermiticosis like five years ago i got my flu shot and after that i developed a localized red skin lesion what's that that's your arthas reaction do you remember serum sickness reaction yep there is something similar called not serum sickness reaction but serum sickness like a reaction oh okay mitochosis first let me tell you what i know about the serum sickness reaction it is type 3 hypersensitivity reaction it's a generalized acute reaction caused by my stupid doctor right very close serum sickness like reaction is kind of similar but not the same it's not caused by the anti-serum or the serum containing the antibodies it's caused by infections or drugs such as hepatitis b virus or medications such as penicillin or monoclonal antibodies causing similar symptoms such as uricaria arthralgia proteinuria fever this is the serum sickness like reaction type 1 type 2 and type 3 hypersensitivity reactions we're dealing with antibodies we're dealing with immoral immunity for the most part but here in type 4 we're talking about cell-mediated immunity for the most part it's not antibodies it's not b lymphocytes it's not hemorrhoidal it is cell mediated it is still lymphocytes that's why it's delayed are you talking about cd40 lymphocytes or cd8 it could be either oh okay tell me the story here is the antigen presenting cells presenting the antigen to the t lymphocytes specifically the cd4 the cd4 secrete and look into the interleukin is the internet of the leukocytes this is how they communicate with each other now the cd4 positive is very active it's going to secrete interleukin-12 also the macrophages secrete in leukem12 don't forget that the macrophages could act as an antigen presenting cell the end result is interleukin 12 activating my th1 t helper one is this the one that help the sister or the neighbor it helps the sister it helps other t lymphocytes it does not help the humoral immunity it helps the sisters the cell-mediated immunity it can also secrete interferon gamma to activate macrophages if the organism is weak destroy it by phagocytosis but what if the organism is nasty and virulent and strong like tuberculosis if i cannot kill it and eat it let me at least surround it in a granuloma the idea that the t helper one cd4 t lymphocytes secretes interferon gamma to activate the macrophage is one of the most commonly tested facts on any exam never ever forget this type 4 we're talking about cell mediated immunity t lymphocytes cd4 cells especially the th1 secrete interferon gamma to activate macrophages low virulence organism phagocytosis high evidence organism making granuloma such as tuberculosis histoplasmosis blast to mitosis coccidioide mycosis or sarcoidosis in this case the granuloma is not against a foreign invader okay mitochosis how can we run circles and make a granuloma around the mycobacterium tuberculosis or the tubercle bacilli let's go let's go here are mycobacterium tuberculosis bacilli we will surround them with whom with macrophages macrophages are here known as epithelioid histiocytes epithelioid because they look like epithelial cells histocytes because they are in the tissue they are not floating freely in the bloodstream when they are floating free in the bloodstream they are called monocytes but here they are stuck in tissues histiocytes don't forget who activated the macrophages t helper 1 are they cd4 or cd8 cd4 t lymphocytes or b lymphocytes t lymphocytes they will also come to run circles around tuberculosis something weird will start to happen many of these macrophages will join forces combined together to make this humongous multinucleated giant cell discovered by langerhans the same scientist who discovered the endocrine cells in your pancreas probably the same doofus who discovered longer han cell histiocytosis aka histiocytosis x discussed in my pulmonology playlist so we have the stupid tb here and then we have our own macrophages called epithelioid cells or epithelioid histiocytes then we have the cd4 t lymphocytes and don't forget some of the macrophages will change into multinucleated giant cells is this an acute destruction no the whole purpose of the granola is that i could not destroy the bacteria acutely therefore this is a chronic thing which means you will need plasma cells okay they can come too more importantly fibroblasts will come what do fibroblasts do they lay down some beautiful fibrous tissue like this oh okay so that you can surround the tuberculosis you can imprison the tb inside this doozy granuloma as long as your immune system remains strong the tb will be in prison for life the moment your immunity drops you're in trouble hashtag tb reactivation that's why tb reactivation is common in the elderly in the immunocompromise in hiv patients in patients with uncontrolled chronic diabetes in patients taking chemotherapy in patients receiving organ transplants in patients taking immunosuppressive drugs such as the biologics it's intercept adelimimab infleximab etc and then what's gonna happen oh let's cause some necrosis okay cell death then yeah let's kill some of those cells all right that's some necrosis for you okay what kind of necrosis is it coagulative necrosis nope this is casey eating necrosis i know it might sound cheesy but that's because it is casey eating means like cheese when you see casey eating granuloma like this you know that there was probably an organism there could be tuberculosis histoplasmosis plastomycosis coccidioideomycosis but that's not true with sarcoidosis there is no organism in the middle in sarcoidosis sarcoidosis is your body attacking itself who else is gonna explain to you like this your woke professor with his power point no give me examples of casey eating granuloma with casey's cheesy necrosis in the center tuberculosis histoplasmosis blasto mycosis coccidioideomycosis basically anything else is going to be non-caseiating granuloma now let's review the four types of hypersensitivity with clinical examples type one this is the example of asthma we have two types of asthma extrinsic which is allergic and intrinsic which is non-allergic this is of course the allergic one because hypersensitivity is a heightened allergy have you ever wondered why we can treat asthma with lipoxygenase inhibitors and leukotriene receptor antagonists yeah because leukotrienes are involved in the late phase of the second exposure to the same freaking antigen could be dust could be pollen ever wonder why we give asthma patients masked cell stabilizers such as chromoline nidocromin ketotifen because they stabilize the mast cells the releasers of histamine have you ever wondered why we have monoclonal antibodies against interleukin 5 for asthma patients yeah because they destroy anilican 5 no analogon 5 no eosinophils can i give this drug to a patient with copd um copd is not caused by eosinophils so most probably not why do we give inhaled steroids for asthma patients because steroids inhibit the production of prostaglandins and locotrons watch my video on the arachidonic acid pathway ever wonder why we have monoclonal antibodies against ige for asthma patients yeah why is aspirin bad for asthma patients because it increases leukotrienes why are beta blockers bad for asthma patients because they block the beta 2 receptor causing bronchoconstriction more wheezing inhaled corticosteroids include buddhisinide and flutica zone the anti-leukotrienes you have the luxe inhibitor xylutin leukotriene receptor antagonist the field has the mast cell stabilizer is chromoline the monoclonal antibody against the eosinophil is been released against ige is amelizumab and don't forget your beta 2 agonists muscarinic antagonists asthma has two things decreased diameter of the bronchi hashtag bronchoconstriction and increased bronchial secretion and this is type 1 hypersensitivity reaction so type 1 what do we have we have asthma now let's talk about type 2 hypersensitivity the complement mediated includes rheumatic fever antiglomerular basement membrane antibody also known as a good pasture syndrome and hyper acute transplant rejection which happens very quickly the surgeon is inserting the new kidney into your body while completing the job the kidney is dying on the spot live what's that hyperacute rejection tell me about the non-complement mediated well if you're talking about adccc this is the story of autoimmune hemolytic anemia immune thrombocytopenia and hemolytic disease of the newborn if you talk about antibodies against the cell surface receptor if you're inhibiting the target most of them are like this example mycenae if you're stimulating the target it's a singular example called graves disease type 3 the generalize if it's not your doctor's fault this is the story of the fibrinoid necrosis immune complex mediated vasculitis nephritis arthritis etc that's lupus and rheumatoid arthritis serum sickness reaction is generalized and acute and this is the reaction to receiving an anti-serum which means serum that has antibodies these are not your own antibodies localized type 3 hyperstitivity is the arthas reaction which means sub acute which means localized this is post vaccine skin reaction type 4 t lymphocytes t lymphocytes tuberculin skin test this is for tuberculosis the granuloma it's for transplantary rejection such as acute rejection chronic rejection but not the hyper acute organ transplant rejection touching what do you mean contact dermatitis this is the story of poison ivy this is the story of wearing a new nickel watch on your wrist and developing a rash on the same wrist and the rash looks exactly like a watch this is the story of trying new makeup and three days later he developed a reaction exactly where he applied the makeup this is also the story of graft versus host disease if you like this video you will adore my renal physiology course available at medicosusperficinetis.com comes with 10 videos 10 cases with notes of course i also have an endocrine pharmacology course learn everything you need to know about insulin the different types of insulin how to calculate the dose of insulin and much more thank you for watching please subscribe hit the bell and click on the join button you can support me here or here go to my website to download my courses be safe stay happy study hard this is medicos's perfect scenarios where medicine makes perfect sense