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This online teaching session covers the topic of Sine and Gravis, focusing on the two types of active immunity, the five immunoglobulin classes, and four Hypersensitivity Reactions. It will give medical professionals an in-depth understanding of neuromuscular transmission and Myasthenia Gravis, a common disorder of neuromuscular transmission. Attendees will become more knowledgeable on immunology, and gain insight into how this disorder is caused, as well as helpful methods for diagnosis and treatment.
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Learning objectives

Learning Objectives: 1. At the end of the lesson, be able to explain the role of active immunity, humoral and cell mediated, in antibody production. 2. Describe the five immunoglobulin classes and their functions. 3. Identify the four types of hypersensitivity reactions, and the characteristic signs and symptoms. 4. Explain the mechanism of neuromuscular transmission and how it can be disrupted in Myasthenia Gravis. 5. Describe the role of the acetylcholine neurotransmitter in neuromuscular transmission.
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The following transcript was generated automatically from the content and has not been checked or corrected manually.

And no. Can you hear me? And yeah, uh we'll stop in two minutes. OK. So today our topic will be uh on Sine and Gravis. So before going on, talking about my and Gravis, I would like to start a bit about the immunology and move on from there. So first of all, I will talk, I would like to talk about uh the active immunity which is found in our uh body that is uh the humoral and salmon immunity. So this uh we humoral immunity that is uh antibody mediator. So we all know we talk about uh antibodies in the rational body. So the similar immunities talking about his anti antibody media production. So we we talk about his pathway of this uh tumor, an uh antibodies, similar antibodies uh when uh when antigen presenting cell that is it can be macrophages or it can be histiocytes or it can be other uh other cells. When they present these antigens, they present these antigens to the T helper cells. These the type of cells, immune cells form in our body. So these uh anti presented by these T helper cells to this B cell. And once the B cells detects these antigens. The B cells then convert into plasma cells. I I showed you these plasma cells from B cells. It converts the plasma cells. These plasma cells then secret antibodies which are specific for this antigen. So this is the humoral pathway which is involved in antibody production. And then another pathway of immunity, active immunity we have is the cell media immunity. Now, the cell me uh cell me uh cell media immunity is uh the same. Uh it starts off with the T helper cells which produce uh uh which uh presents these antigens and release the cytokines. These cytokines then activate the T cyto means these cytotoxic cells, these cytotoxic cells then cause uh uh yeah. Uh the kilo is infected uh but it can activate. So this is like another diagram which shows more specifically what uh each pathway is involved. So here there's antibodies, lysis of phagocytosis of infected cells or the antigens itself. Here, it causes the RS of uh cell me. Uh The cellular immunity causes lysis of uh how about the two types of immunity we have? Moving on now. Uh we need uh So moving on. Now, we will talk about five immunoglobulin classes. These are, these are produced by this uh humoral immune pathway. We have these five immuno immunoglobulin classes. We have the Igmigg Igaigenigt. So these are the five immuno classes which can be found in the body. So when we talk about IgM antibody. It's a pen which means there are 55 antibodies form uh within one IgM. This is the initial antibody which is formed when the in um when the body mounts the immune reaction, this is the in the body, it IgM antibody and uh involving uh complement fixing. So it involves immunity by process complements. Then IgG this IgG it is a mono which has only single uh single antibody. So this is like the classic antibody which shows you all the diagrams. So we talk about is anti part is called FC that is a receptor for the receptor for cells. And this is the antigen binding. These two parts here, this is the antigen binding area. It is like a classic is an IgG is like a secondary immunoglobulin which is produced by his memory cells. So these memories uh uh these uh sorry these cells which are also from uh along with these plasma cells or these B cells, there are cells also form from this uh and uh this type hydro pathways also there are me cells form. So these me cells are formed because if this an condition is presented second time or another time, these uh mammary cells uh will produce this and will mount this reaction. His immune reaction much faster than before. That's the first time moving go on rehab G A uh immunoglobulin. This is a diame which has two pathways and this G is a component along it. So this IG A antibodies is produced along this uh ig A. So around the open tract where is saliva mucus is found. So there is a G I tract tract within this uh all the, the uh the, yeah, I was respirator. They also we can find IG A antibodies. So it ig a the secret antibodies as mentioned if on a mucus, tear saliva or cholesterol, you mean the IgD moma? This IgE mono is very important in this uh antiparasitic activity that is against parasites. The IG is important and also it is involved in anaphylaxis. An ICD monomer antibody is bound to B cell receptors moving on. I would like to ask you a question. I will play uh I ask a question. How many hypersensitive reaction? Uh Yeah. Hi guys. Uh I'm audio, right? Can you hear me? Hello? Can you hear me? Uh You can hear me now? Uh PETA. Right. Right. It's better now, right. Uh Yeah. OK. OK. So I'll put this question again here. Can you tell me how many hyperten reactions you all know? Are there? OK. A A Yeah, it's four types good. So there are four types of uh hypersensitive reaction. So we have type one, type two, type three, type four. There is type five, but it's not very much broken up. These four main types we all know. So type one is IgE mediated. So initially when a particular allergen comes, that is conditional from outside. Uh Now, when you talk about this uh hypersensitive reaction, hypersensitive reaction. It is an abnormal reaction to the external that is a normal uh outside, outside uh allergen or a pollen or some uh uh something like that. It is a, it is normal, it does not mount an immune response. So it's not harmful for you by this. When there's a hypersensitive reaction, produce an abnormal immune response to this outside normal uh object or some uh some uh pollen or something. Or it can be an abnormal reaction to anticancer cells uh found in your own, in your, in your own body itself. So that is what hypersensitive reaction is. So we talk uh moving on, we talk about these four types, uh type ones, IgE media hypertension reactions. So, as I can see, there's there is IgE the antibodies. So this uh first time when this allergen comes to body, these I uh IG receptors, they bind to it. This ma uh ig receptors then uh uh our body is sensitized to this allergen. So these ig uh antibodies are specific for allergen are produced and these IG antibodies bind to this uh mass cell. Uh Second time when this uh allergen comes again, these allergens bind to this uh same uh this, these IG antibodies which produce first time which then really uh cause de of these masses. So this masses uh releases uh histamine uh from cell causing a vari variety of reactions. These are uh as mentioned anaphylaxis or this uh season allergies, eczema hives. So these conditions are a type disease reaction. Uh type two hypersensitive reaction are it is when this uh and uh and these are antibodies. So this uh these are IgG or it can be IG cell e even though it says IGGG it can be IG or IgM cell. These antibodies, they uh bind to cells in our body which can be any cell, but it can be the thyroid. It can be the uh new junction or it can be any receptors. This uh this, that is this FC receptors, they bind to any cells in our body which can mount immune re they mount the immune reaction after that. So that is this uh IgG mediated uh cytotoxic. So it can be cell dependent or it can be complement. Then we have the third type that is complex mediator. So here the antigen is already bounded antigen outside somewhere else. And these I antigen antigen antigen antibody complexes, these roam around the body and deposit multiple places. So these can be in the vessels or it can be in the kidneys or it can be in the lungs or it can depo anywhere along the body. This causes the immune reaction. After the, after the, this, after they bind to this place, they did uh cause the uh damage to these tissues. So these can be g uh these are these examples in arthritis, uh sld or rheumatoid arthritis, uh or those reactions. Then moving on. Now we talk about a type four immune me, uh type four immune reaction, uh type four immune, a type four immune reaction is a cell immediate immune reaction. That is uh when the cytotoxic T cell, these are essential cytotoxic disease to antigen itself. They come and they release the cyto uh cytokines which causes uh cytotoxic T cells to become activated. These can cause damage to uh these things can cause damage to the cells on your own body itself. So, examples of this is uh contact dermatitis or autoimmune disorders, diabetes, multiple sclerosis condition, cell me hypersensitivity. So I guess it's uh it's clear for. So there are four types IG media is type one. Type two is can be IG MRI GG media hypersensitivity. Type three is the immune complex mediated. Type four is cell-mediated moving on. Now, uh coming to myasthenia itself. Now we talk about myasthenia, myasthenia gra is one of the commonest disorder of the neuromuscular transmission. Now, when we talk about the neuromuscular transmission, we talk about neuromuscular transmission first. So as you can see, its number is used to go through. So number one is when action, potential action potentials from these nerves, when they move along, they come to this uh move along the uh the nerves, they will come to this presynaptic cell. So this is a presynaptic presynaptic cell. This is a post synaptic cell, this is a synapse, this is called synapse. So when the action potential comes to this presynaptic cell, they cause the this voltage here, the calcium channel, uh this voltage here, this presynaptic membrane, this action potential. This action potential causes this uh uh calcium channels influx of calcium, this calcium the influx from the outside comes into, into, into the space and tic cell uh into this nerve terminal. So after this ca comes into this chair, the synaptic vesicles, the synaptic vesicles vess which contain aci co and cause the A colon is released into the synaptic ve uh the A colon which is found within the synaptic vesicles. It is then caused to move towards this pre they, they bind to this presynaptic membrane and they cause the release of these neurotransmitters into the synaptic cleft. Uh acho is the acho neurotransmitter, they then bind to the postsynaptic membrane. So what uh the receptors found in these muscles? It is called nico. So the that is the skeletal muscle, 05 urine receptors. There's another type of uh uh I receptor that is a muscarinic receptor which is found in the auto system. So, these uh receptors in the muscle, it is called necrotic receptor. So this a coon comes and binds to this uh nico re test. So in uh a la the transmitter bind to these receptors here, this causes the action potential to start in this post synaptic uh cell. So this action potential then continues along this cell uh and cause muscle. Now, there is an enzyme which is found here uh in the synaptic cleft that is a cholinesterase enzyme. This cholinesterase uh cholinesterase enzyme, it cause this uh neurotransmitter. So this neutrons you were broken down and they taken in back into this pre cell to be re uh to be recycled. Whole transfusion pathway uh occurs where uh action potential comes calcium channel. Uh Where is what is your calcium channels are open? Calcium ines the synaptic vesicles, it goes towards the presynaptic membrane and uh it uh causes the release of these neurotransmitters into the synaptic cleft. These neurotransmitters then bin into membrane contain uh these muco receptors. This causes the action potential to form in this post membrane and continue along this causing the contraction of this muscle. And uh this neurotranse a cholinesterase enzyme which breaks it down as a coli which is the recycle and reuse. So this is the whole neuromuscular OK, which is normally occurs in our body. Now, we're talking about uh uh myasthenia gravis, right? Uh Like to ask you another question. Uh And thank the patient. If anyone could answer the question, I hope ma uh I you can hear me. Yes. Uh Thank you. Yes. So as mentioned here at uh mentioned my gras it is a type two hypersensitive reaction. So it's an autoimmune disease. It's an autoimmune disease. This is because the immuno this uh immune reaction S are, which are found already in our body which is an autoimmune reaction may be autoantibodies. These antibodies are against this ni receptors. Uh these uh form against these nicotinic receptors in the postsynaptic membrane. So they come and bind to these receptors at the neuromuscular junction. So they, when they buy these receptors, the number of receptors found in this posy membrane that decreases as I go on talking about it that decreases. So we talk antibodies. The most commonly found is the Ascoli receptor antibodies. But we also can find the antibodies which can come and bind to these receptors. So we have this muscle specific to kin recept uh muscle special KK uh antibodies or the lipoprotein receptor related protein antibodies. Or uh sometimes there will be no antibody detected in, you know, when we do, we can find so there are se negative uh ma and then so moving on. Now this is the overall of the mi which can change. Uh uh But what we should take from this is that uh the occurrence of uh mascular is it is more common in females than males. That is overall, that is what we should take. Confirm the table that occurrence of ma is more common in females than males. Uh moving on. Uh Now, myasthenia can be a so myasthenia, as I mentioned is an auto disease. Um we should know that autoimmune is all the types of autoimmune diseases. It is associated with other types of autoimmune diseases. So, what I mentioned is some autoimmune diseases. So uh can be hashimoto's graves disease, rheumatid sarcoidosis, sl even the juvenal uh myositis, even those conditions also can be associated with this. My because all of these autoimmune diseases, all autoimmune disease are are associated with other autoimmune diseases. So that's what they are. They confined from this uh this but my itself it can be associated with these conditions. That is a thymoma. It's a benign tumor of the thymus gland can be thymic hyperplasia or that can host graft host reaction is when uh immuno company individual immuno competing individual has A I I in this person, he donates another person, the immune cells found in a donated or they attack the uh recipient. That is a graft first host reaction that can occur after allergic ST transplantation. That is uh allergen me from the same species, same cell transplantation. Now, moving on, I would like to talk about the talk about clinical features. Now, the feature that is the hallmark of my and gravis is this this fatigueability, this fatigueability? I would like to ask you about what do you think fatigueability is? Uh how could you uh can you tell me what fatigueability is? How you all understand by what fatigueability is uh fatigue ability like uh my uh the uh the hallmark of my ability. So how do you understand what this part is? Uh Yes, sir. It's uh essentially muscle weakness. But uh yes, uh like uh ability is mean, I, I explain ability, repeated use of this muscle. There is tiredness and there's weakness of the muscle. So we continues, if we continue to use a particular muscle set that with time, it will uh become weaker and uh become weaker. So that is what this ability means. So I spend the time but it repeated use of muscles that we have a weakness of the muscle. That that is what ability means. This is a hallmark of my gras and a with rest that we you rest, the mu the particular muscles will improve and the weakness will disappear. This occurs because uh so this uh I mentioned here, right, uh this uh receptors, this as this uh antibodies, they come and bind to these receptors, right. So the number of receptors found in this post anti membrane decreases. So even though there's a lot of Ascoli uh normal amount of asri produced here, the number of receptors found here is decreased, which are free receptors and not all asco binds to all the receptors. So the acting membranes, it's a bit decreased. So it's become more and more use it be busy. That is the work. So that is what this particular occurs. And uh that is the hallmark of my and I, so it can occur in multiple places. Muscles are working can be affected by this myasthenia. We can have this ocular mas ocular uh mass that is ocular muscles, that is the commonest. So we can see ptosis. So this is what ptosis is when the eye, the eyelids are drooping downwards. So this is ptosis and this is uh this ptosis is typically asymmetrical. That is actually showing his picture. Again, that 11 side may be affected more than one another side and more than 50% of the patients present with this ptosis or di di double vision. This double vision occurs because the eye muscles that uh superior rectus, inferior rectus, medial lateral rectus, and the superior oblique, inferior, oblique. These are the muscles that are right. So these muscles also can be affected, giving you double vision with the patient. So we should always be uh aware because this can mimic uh uh uh 3rd 4th or six cran pulses. So we should be aware how to differentiate this and that can be lim uh limb uh limb paralysis that is with repeated using of the, the hands and legs that can be fatigue, uh weakness of this or this bum uh bulbar muscles can be affected. This bulbar muscles are associated with uh s uh swallowing and even talking also. So there can be difficulty in swallowing with time. So uh uh then that can be respiratory. This respiratory can occur in a condition like a myasthenia crisis. This is when it's a severe condition like a complication of uh it occurs when there is a severe myasthenia. There is myasthenia crisis. This uh condition, respiratory paralysis can occur that because the muscles are respirator in the diaphragm and the, the intercostal muscles, they can be affected by this. That is a occur that is another potential manifestation which occurs in severe myasthenia. Then moving on. Uh as I mentioned before, this uh massive symptoms are bilateral and it is uh asymmetrical these muscles. These pu pills, bladder and bowel and heart muscles are, these are not affected which all these the pupil, bladder, heart and bowel muscles, these are not affected and the nerve conduction remains normal. The conduction is normal. There's no sensitive deficit, the deep tendon reflexes we check in they was also normal. But if there is repeated neve stimulation, they have decremental response and this is the hall. Now, so when there is repeated nerve, they have a decrement of response. P see in this picture that is a my that we can see the this matrix. Now, it can be seen because there's contraction, there's contraction on this medial portion of the upper. There's uh and also there's horizontal contraction of these corners of this mouth, left medial media. Here, there's contraction, also horizontal, there's contraction of this the the natural, the natural upward smile of the normal person that is lost. So what we see as this GN like thing. So that is called the my snark which you can now moving on. I uh during physical examination of this myasthenia, we can uh do some provocative uh uh measures anything which is we in which there's repetity stimulation, repetitive use of a particular muscle. We can elicit this uh uh fatigueability sign so we can do anything. So these are some, what we uh see here is we can do a sustain uh upward gaze. When you ask the patient look upwards for around 6 to 880 seconds, the uh eyelids just totally start to droop downwards in one of both eyes. So this can occur in uh myasthenia. Then uh this uh manual elevation of this one. If there's, if the patient comes in tosis one wife, we manually elevate that eye, the, the contralateral eye, this contralateral eye that's called the curtain sign or uh it it occurs during the headings in innovation. That is the cause of this, that's called the curtain sign. All right. And then we can do uh another thing with the peak sign that when you type close the eyes tight with, with stand, there will be uh fatigue of dis or because of muscles. But it's clear, the eyes can be slowly seen because the eyes can be ti for a long time. Then we have this uh sustain abduction of the arm sustained if you raise the arms. So seconds, you can uh because this is a weakness, the arms is slowly uh drop downwards. So like that anything that uh causes rapidity stimulation or elicit this particular, this particular hallmark of myasthenia. So we can elicit this sign. We in this clinical diagno uh we can clinically uh diagnose this mass but clinically, it's not important but only die is not uh you enough moving on. We had this my and Gravis uh association which uh classifies my. We have class one is when there's ocular, that is ocular weakness only but the limb muscle weakness, all others are normal. Class two is when there's mild ocular weakness with uh that class II A is uh affecting the limbs or axial muscles where class IB is or muscles are affected. Class three is when there's a moderate weakness. Class four is when there's severe weakness of these muscles. Class five is when the patient requires intubation to survive. So that is class five. So this uh is the classification given uh my Sa American Association. Uh Moving on. Now, we're talking about diagnosis of my myasthenia. Uh We can diagnose with this characteristic fatigue, bit of muscle weakness, that clear hallmark of myasthenia. If we can elicit that we can go 50% route saying it's myasthenia. But we should confirm diagnosis by the presence of these autoantibodies. This serum auto antibody I mentioned earlier, we can confirm by that. Uh but sometimes also measure uh mention that can be se negative uh myasthenia. So if they're negative, we can use electromyography, emg to confirm diagnosis. So we talk about the uh laboratory that we check for the antico receptor antibodies. These are high which are specific for, as I mentioned earlier, specific for myasthenia. We check for that antibodies. But if this antibody is negative, we can for the antibodies also. So those other antibodies you have is this uh anti-mask antibodies or these anti anti I mentioned earlier or there can be anti Arin antibody collagen, two antibodies antibodies, all these potassium channel uh antibodies. So these are new, new antibodies which have been detected. Even if these are there, we can go on with my uh now moving on this is electromyography. The electromyography affected muscle. If the particular muscle affected, we check the electro uh myograph at that group or we can check a rep stimulation of a particular another muscle, another muscle, normal muscle, we can give rapid stimulation to that time project electromyography. So this shows this electromyogram shows there's a decremental response to rapid nerve stimulation as I mentioned. And a chest CT is done. This chest ct is done. This is because the myasthenia is associated with th thymic hyperplasia I mentioned earlier, right? So we should always check uh if the patient has the myasthenia, we should always uh check for this thymoma thymic hyperplasia also. So we do a chest t also we can see uh physicians who percuss the upper the upper sternum area. This is to check for the presence of this thymic mass. So that also can be done uh moving on. Uh we have this phon this not this Troon test, it's not, it's not used anymore that uh uh I don't see anyone using it anymore. That was uh thing of the past I think. So this, when there is a short-acting as uh anticholinesterase that is uh this anticholinesterase, it is uh this phon is a drug name. It's a short-acting antichol antica this antico in inhibits a cholinesterase. So this uh cholinesterase enzyme which I mentioned earlier, it breaks down the aster coli in the synapse. That is this SIA uh the sign up here, the AO here is broke down by the A enzyme. So this is phon, it inhibits that enzyme. So there will be a found in this s so more aster colline uh in the synapse means there's a more uh it there's a high chance of it binding to receptors. So uh better than before the more receptors bound. Even though some receptors are bound by this enzyme bound by uh antibodies, there are more will be bound by this a there's a high chance. So this is the test. So the uh as I mentioned, increase AO in the junction but always when uh doing this test, which the resuscitation facilities available can cause uh respiratory arrest or uh uh sorry uh cardia arrest of conditions like that. So we should always be aware of this condition. So, resuscitation facilities should be available in doing this uh test. So what we can see during this test is that uh when performing this test, the symptoms, these symptoms are such as this drooping of the eyelids or muscle weakness. They, they partially improve with that uh with improve it, they partially improve. But with time, they also go down because it a fun is short acting. Ok. Now another test is ice pack test. So the ice pack test is when you place an ice pack and show you the picture. When you place an ice pack in the affected the eyelids for five minutes, it improves those dose that the doses improves. It raises the eyelids by more than two millimeters. So that is another test we can do. So we uh we check for now, we can do and uh antibody test from me and uh with these two tests, so we can confirm the diagnosis just c to check if there's Thymomas test not done anymore. Uh I expect this is an easy test to do so you can come to a diagnosis with that. Moving on. Now, finally, let's talk about management. Now, pa uh mean management in general management. So if it is a and dr patient and they presented uh respiratory difficulty, we should quickly uh admit them to the hospital and give them proper intensive care, we should give a supportive can avoid excess factors. These exacerbating factors for these myasthenia patients can be uh any infections or it can be trauma surgery. We should always uh be careful when doing that. We should always try to avoid these excess factors and the treatment should be to control the symptoms of myasthenia and not, but uh there is no cure and I will uh answer this question at the end of this uh position, right. So moving on uh pharmac therapy, so we go for pharmacological therapy initially. So the pharmac therapy, we have the anti therapy, as I mentioned earlier, like Xon, we can give you long acting anti antico uh antichol drugs. So these can be mind or you mean neos mind, this will increase, this will increase of per pro amount of A I presenting this uh which which will improve the s of the patient as you know, this is an autoimmune condition. So this is due to uh abnormal immune immunity of our body. So we can give immunosuppressant treatment for this. So these can be steroids uh or it can uh it can be azaTHIOprine cycloSPORINE uh cy uh mycophenolate uh other immunosuppressants which are recently, which can be d approved uh for drugs. We have Eliza, this is an antibody against towards the C five hemoglobin or we had this uh other ig one this or as far as IG one antibody which binds to the HC receptors which reduces circulating IgG. So this cause IgG is what mediates uh this type, this, so these are new, new drugs which have been uh be approved for the for condition then uh if uh lifethreatening signs are respiratory insufficiency or they have dysphagia, difficulty to swallow or the patient is uh uh prepared for surgery and there are significant or if the, if you need a rapid response or the other treatment is uh drug treatments are ineffective or these immunosuppress those are ineffective, we can go for pla which can be in last. Next change is when we uh we take the process from the patient and remove the antibodies and ref uh rep use them with uh we perfuse them with this antibody free plasma. So that is plasma exchange or you can give IV immunoglobulins. Also another d which is uh recently been used is riTUXimab. Uh ri riTUXimab is a drug which uh is uh is an option for treatment of my. And when the first immune immunotherapy, that is these immunosuppressants if they are not useful. RiTUXimab is also a new uh re drug which is being used uh nowadays for. And also uh other things uh I mentioned the presentation but we also should know is the, we should be always careful about neonatal, my and gravis. That is if my gra is a pa mother becomes preg uh pregnant, we should always uh with uh talking about his mother itself. First of all, mastering symptom, these my symptoms, they worsen during pregnancy. That is mostly during the first trimester, these ma symptoms worsen and always um section is required for pregnant patients because they are because they are weak muscles, they can be weak contractions. So, cesarean section is uh mostly preferred because this receptor autoantibodies, they can cross the placenta. They can affect the neon is causing them to have a poor sucking effect of muscle tones between during birth. But we should always uh give them respiratory support, give, give them IV feeding and also mo monitor them in the new to ICU. So these things should be always be careful when check and uh that's all uh for today's session. I, I hope that was very informative for her, the feedback form to get your certificates. I hope. But.