WEBVTT 00:00:08.041 --> 00:00:10.477 Hello everyone. 00:00:10.477 --> 00:00:14.514 Today we're back together and we're going to be talking about hypersensitivity. 00:00:14.781 --> 00:00:18.818 Again we're going to be talking about hypersensitivity 00:00:18.985 --> 00:00:21.988 types two, three and four. 00:00:22.455 --> 00:00:26.659 Remember hypersensitivity is nothing different 00:00:26.893 --> 00:00:29.362 than the regular immune response. 00:00:29.362 --> 00:00:33.166 But it's a heightened or an exaggerated immune response 00:00:33.633 --> 00:00:37.037 where you have inappropriate reactions 00:00:37.270 --> 00:00:40.273 or you have damage to the host. 00:00:41.241 --> 00:00:44.244 If you remember, the Jelen Coombs classification system 00:00:44.244 --> 00:00:48.114 said there were four main types of hypersensitivity, 00:00:48.581 --> 00:00:53.553 and they were classified in terms of the mechanisms 00:00:53.553 --> 00:00:56.523 that were involved in the hypersensitivity. 00:00:58.258 --> 00:01:02.295 Today, we're going to be talking about types two, three and four. 00:01:02.328 --> 00:01:05.031 Hypersensitivity is 00:01:05.031 --> 00:01:07.700 before we go into types two, three and four 00:01:07.700 --> 00:01:12.572 I just want to review a little bit about type one hypersensitivity 00:01:12.906 --> 00:01:15.909 to get you a perspective of where we're going. 00:01:16.409 --> 00:01:21.314 Type one hypersensitivity as you remember, is called immediate hypersensitivity 00:01:21.681 --> 00:01:25.452 because reactions occur within a minute or two 00:01:26.219 --> 00:01:29.722 of, exposure to whatever the allergen is. 00:01:30.223 --> 00:01:34.461 IgG class antibody is the type that's involved. 00:01:35.161 --> 00:01:37.530 The other major components in type one 00:01:37.530 --> 00:01:40.600 hypersensitivity are the mast cells and base of cells. 00:01:42.902 --> 00:01:45.105 A type one hypersensitivity 00:01:45.105 --> 00:01:48.108 response occurs in three phases. 00:01:48.842 --> 00:01:52.846 The first phase is the sensitization phase and that was. 00:01:53.179 --> 00:01:55.915 That is, when a person is exposed 00:01:55.915 --> 00:02:01.521 to an allergen for the first time, IgG antibodies get formed 00:02:01.788 --> 00:02:04.791 and they immediately go and attach themselves to 00:02:05.892 --> 00:02:08.761 mast cells and basic cells throughout the body. 00:02:08.761 --> 00:02:12.065 And those cells are now called sensitized. 00:02:13.533 --> 00:02:16.703 On subsequent exposures to the allergen, 00:02:17.403 --> 00:02:20.507 you have the activation phase, and that is where 00:02:22.008 --> 00:02:25.011 you see antigens 00:02:25.578 --> 00:02:30.617 and antibodies being cross-linked on the base of cells, 00:02:31.184 --> 00:02:35.054 causing tissue changes in the cell membrane on the base of cells 00:02:35.388 --> 00:02:39.025 and release of mediators into the body. 00:02:40.360 --> 00:02:42.529 The third phase is the effector phase, 00:02:42.529 --> 00:02:48.668 where the other mediators are sent out from the mast cells and base fills, 00:02:48.835 --> 00:02:51.804 and they go to effector sites throughout the body. 00:02:51.804 --> 00:02:54.941 Histamine is probably the most important one of these, 00:02:54.941 --> 00:02:57.010 but there are other mediators. 00:02:57.010 --> 00:03:00.613 The result is your allergic response, 00:03:01.014 --> 00:03:04.584 and it can range anywhere from hay fever, 00:03:05.852 --> 00:03:08.221 stomach pains 00:03:08.221 --> 00:03:11.124 to the really serious action 00:03:11.124 --> 00:03:14.127 where it could result in anaphylaxis. 00:03:14.394 --> 00:03:17.330 So today, as we go into types two, 00:03:17.330 --> 00:03:21.100 three and four hypersensitivity, we're going 00:03:21.100 --> 00:03:24.704 to be talking about what other players are going to be involved 00:03:25.138 --> 00:03:28.575 in those hyper sensitivities and their mechanisms 00:03:28.575 --> 00:03:31.578 of action. 00:03:32.812 --> 00:03:33.646 Type two 00:03:33.646 --> 00:03:37.650 hypersensitivity is also called antibody dependent 00:03:37.850 --> 00:03:41.821 cytotoxic hypersensitivity or simply 00:03:42.555 --> 00:03:45.558 cytotoxic hypersensitivity. 00:03:46.459 --> 00:03:51.097 The mechanism involved in type type two is caused 00:03:51.097 --> 00:03:56.402 when antibody attaches directly to an antigen on a cell membrane, 00:03:57.237 --> 00:04:00.273 and the results of the antibody attachment causes cell 00:04:00.273 --> 00:04:03.243 lysis or tissue destruction. 00:04:04.410 --> 00:04:07.680 The culprit antibodies here are IgG 00:04:07.714 --> 00:04:10.717 and AGM. 00:04:12.051 --> 00:04:13.253 One antibody coats 00:04:13.253 --> 00:04:17.257 the cell surface, leaving its FC fragments exposed. 00:04:17.590 --> 00:04:20.426 What can happen? 00:04:20.426 --> 00:04:21.961 Several things. 00:04:21.961 --> 00:04:26.099 One of them could be phagocytosis of the cell. 00:04:27.333 --> 00:04:27.800 Another 00:04:27.800 --> 00:04:33.006 thing might be natural killer cells would come and destroy 00:04:33.006 --> 00:04:36.075 the antigen target and complement 00:04:36.075 --> 00:04:39.078 could be activated. 00:04:39.212 --> 00:04:43.383 Complement plays a very important role in type two hypersensitivity. 00:04:43.983 --> 00:04:48.221 If complement cascades down through the C9 stage, 00:04:48.621 --> 00:04:52.692 or forms that Mac complex C5 through nine, 00:04:53.359 --> 00:04:56.362 cell destruction or lysis could occur. 00:04:56.829 --> 00:05:01.901 If the cascade only goes to the C3 stage, 00:05:02.201 --> 00:05:05.171 C3, B could coat the cell service 00:05:05.171 --> 00:05:08.174 and that would enhance phagocytosis. 00:05:11.944 --> 00:05:13.946 This seems like a very good thing. 00:05:13.946 --> 00:05:17.617 We want this kind of immune response to take place. 00:05:17.984 --> 00:05:22.655 If the offending cell is like a bacteria, 00:05:23.356 --> 00:05:26.359 we only call it a hypersensitivity. 00:05:28.227 --> 00:05:29.595 When it's our own cells 00:05:29.595 --> 00:05:33.032 that are being destroyed, or it's cells 00:05:33.032 --> 00:05:36.069 that we want to survive inside our body 00:05:36.235 --> 00:05:39.906 like a transplant or a transfusion. 00:05:41.341 --> 00:05:43.643 Let me give you some examples of type 00:05:43.643 --> 00:05:47.113 two hypersensitivity reactions. 00:05:47.680 --> 00:05:50.783 The first is a transfusion reaction. 00:05:51.884 --> 00:05:55.988 In this case, the patient has developed antibodies 00:05:56.356 --> 00:06:01.627 against red blood cell antigens that he or she lacks. 00:06:02.228 --> 00:06:07.200 Then when he receives a transfusion of that kind of blood, 00:06:07.967 --> 00:06:12.472 his antibodies will attack those transfused cells. 00:06:13.039 --> 00:06:16.042 They're incompatible with him. 00:06:16.142 --> 00:06:19.846 The antibody coated cells will be removed by the spleen, 00:06:20.380 --> 00:06:23.783 or if complement is triggered and goes 00:06:23.783 --> 00:06:26.853 through its full cycle, they'll be destroyed. 00:06:28.020 --> 00:06:30.423 Hemolysis could be delayed in mild, 00:06:30.423 --> 00:06:33.659 or it could be severe and potentially fatal. 00:06:34.861 --> 00:06:37.797 Usually when we talk about transfusion 00:06:37.797 --> 00:06:43.102 reactions, the most serious and most quick to occur 00:06:43.102 --> 00:06:47.640 are those involving the Abo blood group system. 00:06:48.241 --> 00:06:51.644 And I'm sure you're aware of certain blood 00:06:51.677 --> 00:06:55.948 types are compatible with other blood types, and some aren't, 00:06:56.582 --> 00:07:00.086 because people naturally have antibodies 00:07:00.453 --> 00:07:04.457 that occur against the blood cell, the blood type 00:07:04.657 --> 00:07:06.859 that they do not possess. 00:07:06.859 --> 00:07:11.130 So when a person will have antibody antibodies, 00:07:11.431 --> 00:07:14.367 if they're transfused with B, b, 00:07:15.435 --> 00:07:16.636 blood cells, 00:07:16.636 --> 00:07:20.840 they will have an immune response to it and there will be a transfusion reaction. 00:07:20.840 --> 00:07:23.843 Second example of a type two reaction 00:07:23.943 --> 00:07:26.946 is hemolytic disease of the newborn. 00:07:27.313 --> 00:07:29.982 This is causing destruction 00:07:29.982 --> 00:07:32.985 of cells in the fetus and the newborn. 00:07:33.820 --> 00:07:36.823 If the mother has 00:07:36.956 --> 00:07:40.092 IgG type antibodies against an antigen 00:07:40.092 --> 00:07:43.863 that the fetus possesses, which she lacks, the 00:07:45.465 --> 00:07:48.968 those IgG antibodies could cross the placenta 00:07:49.368 --> 00:07:52.905 and attach to the fetal red blood cells, 00:07:53.272 --> 00:07:57.043 causing tissue destruction, anemia, 00:07:57.710 --> 00:08:01.814 or in a serious case, it could cause death of the fetus. 00:08:02.448 --> 00:08:06.486 This reaction is not going to occur during a first pregnancy, 00:08:06.986 --> 00:08:10.089 because during the first pregnancy is 00:08:10.089 --> 00:08:13.860 when the mother is first exposed to the fetal antigen, 00:08:14.293 --> 00:08:17.296 but in the case of RH, 00:08:17.797 --> 00:08:21.200 if she is RH negative, she's had an RH positive 00:08:21.200 --> 00:08:24.203 child, has developed the antibodies 00:08:24.370 --> 00:08:28.508 and now has a second pregnancy within RH positive child. 00:08:28.774 --> 00:08:32.478 That's when you can see this reaction and it could occur. 00:08:32.478 --> 00:08:32.912 Then. 00:08:36.916 --> 00:08:38.818 A third example of a type two 00:08:38.818 --> 00:08:43.022 hypersensitivity is autoimmune hemolytic anemia. 00:08:44.156 --> 00:08:47.960 This is an example where the patient has developed 00:08:47.960 --> 00:08:50.963 antibodies against self antigens 00:08:51.030 --> 00:08:54.033 on his own red blood cells. 00:08:54.600 --> 00:08:56.369 Autoimmune hemolytic anemia. 00:08:56.369 --> 00:08:59.372 These are classified as either cold or warm 00:08:59.572 --> 00:09:02.875 depending on the optimal temperature of reactivity. 00:09:04.610 --> 00:09:05.111 Cold. 00:09:05.111 --> 00:09:09.415 Autoimmune hemolytic anemia is seen more often in older persons. 00:09:11.551 --> 00:09:12.418 This antibody 00:09:12.418 --> 00:09:15.655 reaction occurs when blood in the extremities 00:09:15.922 --> 00:09:18.958 goes to lower than 30°C, 00:09:19.659 --> 00:09:22.828 and if the antibody is a IDM 00:09:22.862 --> 00:09:26.599 class, it will attach to the red blood cell antigen. 00:09:26.866 --> 00:09:31.904 Then, as the blood warms up again, the IDM will be released. 00:09:32.305 --> 00:09:37.710 But C3B can still remain on the red blood cells 00:09:37.710 --> 00:09:42.882 and cause destruction or decreased red cell survival at a later time. 00:09:43.749 --> 00:09:47.420 Warm autoimmune hemolytic anemia does occur 00:09:47.420 --> 00:09:51.724 at temperatures above 37 degrees at body temperature. 00:09:52.725 --> 00:09:54.093 In all of these cases, 00:09:54.093 --> 00:09:57.663 it could cause anemia or even serious anemia 00:09:58.030 --> 00:10:01.033 in the patient. 00:10:01.834 --> 00:10:03.603 We also call it a type 00:10:03.603 --> 00:10:06.606 two hypersensitivity reaction. 00:10:06.872 --> 00:10:09.775 In some cases where antibodies 00:10:09.775 --> 00:10:13.012 are autoantibodies against self tissues, 00:10:13.579 --> 00:10:16.582 good pasture syndrome is one of these. 00:10:17.483 --> 00:10:22.054 In good pastures, antibody reacts with the basement membrane protein 00:10:22.054 --> 00:10:27.660 in the kidneys, complement is activated, inflammation occurs 00:10:28.094 --> 00:10:31.097 and the kidneys are damaged. 00:10:31.664 --> 00:10:34.133 In insulin dependent diabetes 00:10:34.133 --> 00:10:37.203 mellitus, the patient has antibodies 00:10:37.470 --> 00:10:41.007 that attaches to the islet cells in the pancreas. 00:10:41.941 --> 00:10:44.944 The cells become inflamed and destroyed. 00:10:45.611 --> 00:10:48.547 Insulin is no longer produced 00:10:48.547 --> 00:10:51.584 and the patient suffers from diabetes. 00:10:54.487 --> 00:10:55.921 There are ways to test 00:10:55.921 --> 00:10:58.924 for type two hypersensitivity. 00:11:00.126 --> 00:11:02.228 One of the first ways is the anti 00:11:02.228 --> 00:11:05.898 globulin test, sometimes called the Coombs test, 00:11:06.332 --> 00:11:09.168 and there is a direct anti globulin test and 00:11:09.168 --> 00:11:12.271 an indirect in the de T. 00:11:13.773 --> 00:11:16.409 We're looking to see if red blood cells 00:11:16.409 --> 00:11:19.412 have been coded with IgG antibody 00:11:19.578 --> 00:11:22.581 or complement. 00:11:23.082 --> 00:11:27.353 The De is used to investigate hemolytic disease of the newborn, 00:11:27.353 --> 00:11:31.691 transfusion reactions, and autoimmune hemolytic anemia. 00:11:32.258 --> 00:11:35.494 It's a lab test where we're actually looking to see 00:11:35.928 --> 00:11:40.032 is there antibody or complement on the red blood cells. 00:11:40.933 --> 00:11:45.705 The indirect anti globulin test is used to see 00:11:45.705 --> 00:11:50.376 if the patient has antibodies against red cell antigens. 00:11:51.844 --> 00:11:55.581 And we use it when we're performing a cross match 00:11:55.815 --> 00:11:58.651 to see if the transfused cells 00:11:58.651 --> 00:12:01.921 are going to be compatible with the recipient. 00:12:02.822 --> 00:12:05.725 And we'll also use it to investigate 00:12:05.725 --> 00:12:08.728 a transfusion reaction that has occurred. 00:12:10.730 --> 00:12:12.531 We can also do specific 00:12:12.531 --> 00:12:16.335 antibody tests for type two hypersensitivity. 00:12:16.769 --> 00:12:20.606 And in those cases, we would be looking in the patient's 00:12:20.606 --> 00:12:24.710 serum to see if he has antibodies against 00:12:24.710 --> 00:12:27.880 whatever antigen it is that we're looking for. 00:12:28.714 --> 00:12:32.017 In the two cases that I'm showing 00:12:32.051 --> 00:12:36.722 today, you're going to be looking for either glomerular basement 00:12:36.722 --> 00:12:40.526 membrane antibodies in the case of good pasture syndrome 00:12:40.826 --> 00:12:45.030 or islet cell antibodies in the case of diabetes mellitus. 00:12:47.366 --> 00:12:50.269 This particular reaction is 00:12:50.269 --> 00:12:53.506 a fluorescent reaction where tissue 00:12:53.506 --> 00:12:56.509 is put on a glass slide. 00:12:56.542 --> 00:12:59.545 Patient serum is incubated with the tissue, 00:12:59.912 --> 00:13:03.883 and if the patient has antibody to the antigen, it will attach. 00:13:04.917 --> 00:13:09.421 Then when we add a fluorescent anti-human globulin 00:13:09.722 --> 00:13:11.857 and look at it under the fluorescent microscope, 00:13:11.857 --> 00:13:16.362 we'll be able to see the results and the tissue staining patterns. 00:13:16.862 --> 00:13:19.832 Let's move on to type three hypersensitivity. 00:13:19.899 --> 00:13:22.902 This is called immune complex hypersensitivity. 00:13:24.236 --> 00:13:27.239 The mechanism is soluble. 00:13:27.239 --> 00:13:30.242 Antigen and antibody combine 00:13:30.242 --> 00:13:33.245 to form insoluble immune complexes, 00:13:33.779 --> 00:13:37.149 which precipitate and deposit in the tissues. 00:13:38.317 --> 00:13:42.121 Inflammation and tissue damage occur, 00:13:42.721 --> 00:13:45.691 and that is the reaction that we see 00:13:45.691 --> 00:13:48.694 inside the host. 00:13:50.029 --> 00:13:53.432 I'll explain the mechanism of type three hypersensitivity 00:13:53.732 --> 00:13:58.070 by going into the three components that are involved in the phenomenon. 00:13:58.804 --> 00:14:02.975 And the first is small immune complexes. 00:14:04.577 --> 00:14:06.512 Immune complexes are normally 00:14:06.512 --> 00:14:10.583 found in the immune response antigen antibody. 00:14:10.583 --> 00:14:15.421 Combined this triggers complement UPS and ization 00:14:15.421 --> 00:14:18.424 and lysis of the foreign antigen occurs 00:14:18.924 --> 00:14:22.294 and hopefully the infection is resolved. 00:14:23.863 --> 00:14:26.632 In type three hypersensitivity, 00:14:26.632 --> 00:14:29.668 the immune complexes are a little bit different. 00:14:32.404 --> 00:14:35.407 The antigen is usually a very small 00:14:35.774 --> 00:14:38.777 but persistent antigen, 00:14:39.778 --> 00:14:42.781 like a chronic microbial infection 00:14:43.015 --> 00:14:46.952 or an environmental agent like dust or mold 00:14:47.686 --> 00:14:51.724 or perhaps a self component such as your own DNA. 00:14:52.925 --> 00:14:57.162 The antibody involved is usually of the IgG class, 00:14:57.596 --> 00:15:00.332 sometimes AGM, 00:15:00.332 --> 00:15:03.569 because the antigen is so persistent 00:15:03.936 --> 00:15:06.739 and it's small and soluble, 00:15:06.739 --> 00:15:09.875 only small immune complexes form. 00:15:10.743 --> 00:15:13.746 They are not big enough to get 00:15:15.047 --> 00:15:16.849 the complement system 00:15:16.849 --> 00:15:19.852 involved or phagocytosis, 00:15:19.952 --> 00:15:22.221 immediately to clear the infection. 00:15:22.221 --> 00:15:27.226 The antibody is usually of the IgG class, but it could be of AGM. 00:15:27.826 --> 00:15:30.963 The reason why these immune complexes are different 00:15:31.130 --> 00:15:35.367 is because they don't get taken out by the immune system. 00:15:35.567 --> 00:15:38.070 Phagocytosis isn't occurring. 00:15:38.070 --> 00:15:40.873 Instead, the small immune complexes 00:15:40.873 --> 00:15:45.044 deposit in the capillaries or tissues inside the body. 00:15:52.251 --> 00:15:55.554 This activates the next part of the component 00:15:55.554 --> 00:15:58.557 in type three hypersensitivity, which is complement. 00:15:59.491 --> 00:16:04.029 Once complement is triggered, several things can occur again. 00:16:04.029 --> 00:16:06.031 Optimization. 00:16:06.031 --> 00:16:09.001 So there is 00:16:09.101 --> 00:16:12.304 destruction of the immune complex 00:16:13.439 --> 00:16:16.475 or there could be cell lysis occurring. 00:16:17.276 --> 00:16:21.480 Complement also will attract neutrophils to the area, 00:16:21.780 --> 00:16:25.517 which are the third component of a type three reaction. 00:16:26.452 --> 00:16:30.022 The neutrophils are attracted and they come in 00:16:30.022 --> 00:16:34.760 and they try to do their job of engulfing or phagocytes 00:16:34.793 --> 00:16:39.665 izing the offending tissue and immune complex. 00:16:40.032 --> 00:16:43.435 But in this case they're not effective in cleaning up the problem. 00:16:44.136 --> 00:16:46.772 The reason is, is because 00:16:46.772 --> 00:16:50.142 the neutrophils can't engulf the cells 00:16:50.476 --> 00:16:53.612 or the tissue where the immune complexes have settled. 00:16:54.513 --> 00:16:58.283 So the the the neutrophils become frustrated. 00:16:58.617 --> 00:17:01.620 They go through a process called exocytosis. 00:17:02.187 --> 00:17:06.091 And they release their enzymes into the environment. 00:17:06.792 --> 00:17:10.996 These proteolytic enzymes then damage the local tissue. 00:17:11.730 --> 00:17:16.101 They intensify the inflammation and scar tissue develops. 00:17:17.202 --> 00:17:18.170 So we've got a 00:17:18.170 --> 00:17:21.173 normal immune reaction going on. 00:17:21.306 --> 00:17:26.512 But unfortunately the immune complexes are small and settled into the tissues 00:17:26.712 --> 00:17:29.715 where they can't be removed from the system. 00:17:29.915 --> 00:17:32.551 Tissue destruction occurs. 00:17:32.551 --> 00:17:35.220 An example of an immune complex 00:17:35.220 --> 00:17:39.058 hypersensitivity is the reaction. The. 00:17:39.258 --> 00:17:44.863 This reaction is an experimentally induced localized 00:17:44.930 --> 00:17:48.267 skin reaction of type three hypersensitivity. 00:17:50.369 --> 00:17:51.270 Mr. Arthas 00:17:51.270 --> 00:17:54.339 or Doctor Arthas was the one who developed 00:17:54.573 --> 00:17:57.509 this particular experiment, 00:17:57.509 --> 00:18:00.412 and it's something I. 00:18:00.412 --> 00:18:03.382 I have no idea why he would have developed it. 00:18:03.382 --> 00:18:08.353 What Doctor Arthas did is he injected an animal with small amounts 00:18:08.353 --> 00:18:12.458 of a particular antigen, inducing the animal to build up 00:18:12.458 --> 00:18:16.662 lots and lots of IgG antibodies against that antigen. 00:18:17.296 --> 00:18:20.933 Then what he did is he injected a small amount 00:18:20.933 --> 00:18:24.002 of that antigen into the animal skin, 00:18:25.504 --> 00:18:28.507 and within a few hours, 00:18:29.641 --> 00:18:34.079 the poor animal began to develop an interaction 00:18:34.379 --> 00:18:38.283 and swelling and redness in the area 00:18:38.283 --> 00:18:41.286 where he had injected the antigen, 00:18:42.187 --> 00:18:45.190 something that is type three hypersensitivity, though, 00:18:45.324 --> 00:18:48.927 is serum sickness, and this was common 00:18:49.194 --> 00:18:53.132 before antibiotic therapy was really being used. 00:18:53.732 --> 00:18:57.302 It's caused by passive immunization 00:18:57.903 --> 00:19:01.240 using animal serum antitoxin in, 00:19:01.673 --> 00:19:06.078 a person, let's say the person was bitten by a snake 00:19:07.212 --> 00:19:10.349 and we needed to use antitoxin 00:19:10.682 --> 00:19:14.620 to quick neutralize the venom that was there. 00:19:15.120 --> 00:19:18.157 Well, that antivenom would have been made in a horse, 00:19:18.624 --> 00:19:21.560 and that horse antiserum would be given 00:19:21.560 --> 00:19:24.563 to the patient. 00:19:24.663 --> 00:19:26.298 Nice that it clears up 00:19:26.298 --> 00:19:29.735 the infection of the snake bite. 00:19:30.002 --> 00:19:33.205 Unfortunately, all of those extra horse proteins 00:19:33.438 --> 00:19:37.609 that were in the immunization persisted 00:19:37.609 --> 00:19:41.346 in the patient's body, and the patient developed antibodies 00:19:42.481 --> 00:19:45.450 secondarily to the horse proteins 00:19:46.185 --> 00:19:49.054 and immune complexes would occur from 00:19:49.054 --> 00:19:54.626 that settle in the joints and for a few days to a few weeks, 00:19:55.127 --> 00:19:59.164 the patient would have, fever and chills, 00:19:59.631 --> 00:20:02.634 joint symptoms, rash, 00:20:03.335 --> 00:20:07.472 and the infection would clear itself up within a few days. 00:20:08.507 --> 00:20:11.210 There are also autoimmune diseases 00:20:11.210 --> 00:20:15.480 that are caused by a type three hypersensitivity reaction. 00:20:16.048 --> 00:20:18.817 One of those you've probably heard of, it's 00:20:18.817 --> 00:20:21.820 systemic lupus erythematosus. 00:20:22.020 --> 00:20:27.092 In this case, the antigen is actually self DNA 00:20:27.426 --> 00:20:30.629 or other, nuclear components. 00:20:31.129 --> 00:20:35.234 When the patient develops autoimmune antibodies to these. 00:20:35.534 --> 00:20:40.472 As you can imagine, this is a very persistent antigen your own DNA. 00:20:41.039 --> 00:20:44.743 So small immune complexes are constantly forming 00:20:46.078 --> 00:20:47.646 in lupus. 00:20:47.646 --> 00:20:50.115 The patient will have 00:20:50.115 --> 00:20:53.285 intermittent inflammatory episodes. 00:20:53.986 --> 00:20:58.123 We'll have joint and kidney problems. 00:20:58.890 --> 00:21:01.560 We'll have cells and immune 00:21:01.560 --> 00:21:04.830 complexes settling on their membrane surfaces. 00:21:06.698 --> 00:21:09.501 Rheumatoid arthritis. 00:21:09.501 --> 00:21:11.303 Rheumatoid arthritis 00:21:11.303 --> 00:21:14.306 is another immune complex 00:21:15.207 --> 00:21:18.210 and autoantibody type reaction. 00:21:18.810 --> 00:21:21.913 In rheumatoid arthritis, the antigen is 00:21:21.913 --> 00:21:25.117 the patient's own IgG antibodies. 00:21:25.517 --> 00:21:28.820 So yes, the patient has developed antibodies 00:21:28.820 --> 00:21:31.823 against his own antibodies. 00:21:31.890 --> 00:21:34.893 Again a very persistent antigen. 00:21:35.160 --> 00:21:39.464 Small immune complexes could form and the patient suffers 00:21:39.765 --> 00:21:43.201 mainly with immune complexes settling in the joints. 00:21:43.568 --> 00:21:46.571 So they'll have swollen and painful joints. 00:21:48.006 --> 00:21:51.476 So just to recap of type three hypersensitivity 00:21:52.344 --> 00:21:55.347 soluble antigen is involved. 00:21:55.947 --> 00:21:59.151 Soluble antigen that is persistent 00:21:59.151 --> 00:22:02.521 and usually quite small in size. 00:22:03.422 --> 00:22:06.792 IgG or IgG GM antibodies form 00:22:06.792 --> 00:22:10.162 immune complexes with the antigen. 00:22:11.496 --> 00:22:14.599 Those immune complexes are not removed from the body. 00:22:15.000 --> 00:22:20.272 They go and deposit into the patient's tissues where complement is activated, 00:22:20.572 --> 00:22:23.442 and neutrophils D granule light 00:22:23.442 --> 00:22:26.445 causing inflammation and tissue damage. 00:22:26.945 --> 00:22:30.349 Type four hypersensitivity is also called 00:22:30.349 --> 00:22:34.353 cell mediated hypersensitivity or delayed type. 00:22:34.786 --> 00:22:38.924 It differs from the first three types of hypersensitivity 00:22:39.224 --> 00:22:43.862 because antibodies and complement are not involved. 00:22:44.229 --> 00:22:47.099 It is cell mediated immunity. 00:22:47.099 --> 00:22:50.602 Only T cells are involved in this case. 00:22:53.205 --> 00:22:55.440 The symptoms take place 00:22:55.440 --> 00:22:59.010 within 48 to 72 hours 00:22:59.244 --> 00:23:02.247 after exposure to the antigen. 00:23:02.614 --> 00:23:05.617 The mechanism is what you would see in 00:23:05.617 --> 00:23:08.820 any cell mediated immunity type response. 00:23:09.321 --> 00:23:11.790 Patient is exposed to antigen. 00:23:11.790 --> 00:23:14.960 The antigen presenting cells process 00:23:14.960 --> 00:23:17.963 the antigen and present it to T cells. 00:23:18.230 --> 00:23:21.800 In this case, the T cells will produce lymphocytes 00:23:22.134 --> 00:23:25.771 that attract other cells to the area. 00:23:26.972 --> 00:23:30.008 Macrophages, neutrophils, and cytotoxic 00:23:30.008 --> 00:23:33.011 T cells are recruited to the area. 00:23:34.112 --> 00:23:35.947 In a regular immune response. 00:23:35.947 --> 00:23:38.950 The infected cell would be eliminated. 00:23:39.918 --> 00:23:42.821 This is what we expect to happen. 00:23:42.821 --> 00:23:46.458 Cell mediated immunity in almost all cases 00:23:46.458 --> 00:23:50.796 results in some sort of tissue destruction because 00:23:51.930 --> 00:23:54.766 the antigen has gone intracellular. 00:23:54.766 --> 00:23:58.670 So to get rid of a virus, we we need our immune system 00:23:58.670 --> 00:24:02.340 to destroy the cell that the virus is housed in. 00:24:03.975 --> 00:24:04.843 But when we get to 00:24:04.843 --> 00:24:08.580 type four hypersensitivity there's an overreaction. 00:24:08.914 --> 00:24:11.583 There's a heightened immune response. 00:24:11.583 --> 00:24:15.120 And it causes more tissue destruction 00:24:15.387 --> 00:24:18.390 than the original antigen might have caused. 00:24:18.924 --> 00:24:21.860 Some of the lymph nodes that are involved in type 00:24:21.860 --> 00:24:25.530 four hypersensitivity are interleukin two, 00:24:26.565 --> 00:24:30.469 interferon gamma, and tumor necrosis factor. 00:24:32.204 --> 00:24:34.206 If cytotoxic T cells 00:24:34.206 --> 00:24:39.010 are recruited to the area, they can make direct contact 00:24:39.344 --> 00:24:42.714 with the affected cell and go ahead 00:24:42.714 --> 00:24:45.717 and destroy the cell. 00:24:47.986 --> 00:24:51.289 For some examples of delayed type hypersensitivity, 00:24:51.690 --> 00:24:56.261 the first one I want to tell you about is contact dermatitis. 00:24:56.595 --> 00:25:01.333 You've all heard of poison ivy and the kind of rash 00:25:01.600 --> 00:25:04.603 that it could cause. 00:25:04.669 --> 00:25:07.172 This is a type for hypersensitivity 00:25:07.172 --> 00:25:10.175 reaction. 00:25:10.208 --> 00:25:13.345 It's also called contact dermatitis. 00:25:13.778 --> 00:25:16.615 And besides 00:25:16.615 --> 00:25:18.350 poison ivy, poison oak, 00:25:18.350 --> 00:25:23.922 poison sumac, people can have reactions to things such as nickel rubber, 00:25:24.256 --> 00:25:27.826 latex, various soaps and cosmetics, 00:25:28.894 --> 00:25:32.297 PBA that was used in sunscreens. 00:25:33.031 --> 00:25:37.435 In these cases, the antigen itself is a captain. 00:25:37.569 --> 00:25:40.572 It's a very small 00:25:40.972 --> 00:25:42.908 particle 00:25:42.908 --> 00:25:46.111 which normally wouldn't be immunogenic, but 00:25:47.879 --> 00:25:50.081 as it forms and meets 00:25:50.081 --> 00:25:53.084 with a carrier, it acts as a captain. 00:25:53.118 --> 00:25:58.023 And then when it is presented to the antigen presenting cells inside your body, 00:25:58.223 --> 00:26:04.029 it is seen as foreign and the body develops its immune response to that. 00:26:04.029 --> 00:26:07.032 Captain carrier complex. 00:26:08.867 --> 00:26:11.903 The T-cells, once they're involved, recruit 00:26:11.903 --> 00:26:16.875 and activate macrophages, and the result is a day or two later. 00:26:17.175 --> 00:26:20.412 You're going to see the rash of the poison ivy 00:26:20.845 --> 00:26:24.583 or the nickel jewelry or whatever 00:26:24.583 --> 00:26:27.586 the offending substance is. 00:26:29.220 --> 00:26:32.290 Hypersensitivity pneumonitis is another example. 00:26:32.524 --> 00:26:35.760 You might have heard of this as farmers, 00:26:35.760 --> 00:26:38.730 lung or pigeon carriers disease. 00:26:38.763 --> 00:26:41.232 Hypersensitivity pneumonitis is 00:26:41.232 --> 00:26:44.769 another example of type four hypersensitivity. 00:26:45.270 --> 00:26:49.808 You might have heard of this as farmers lung disease or something. 00:26:50.008 --> 00:26:55.013 It's most common in men aged about 30 to 50. 00:26:55.246 --> 00:26:59.851 In this case, the antigen is dust or its mold 00:27:00.251 --> 00:27:05.156 or its little little particles of oats or hay 00:27:05.790 --> 00:27:08.760 that the patient is chronically inhaling. 00:27:08.893 --> 00:27:13.198 And it affects the T cells inside the lungs. 00:27:14.499 --> 00:27:16.434 It's a type 00:27:16.434 --> 00:27:19.771 for hypersensitivity because it's the white blood cells 00:27:19.771 --> 00:27:22.774 that are involved, not antibodies. 00:27:25.577 --> 00:27:26.011 A third 00:27:26.011 --> 00:27:31.716 very interesting one is the tuberculin reaction, the tuberculosis skin test 00:27:32.150 --> 00:27:36.721 that a lot of people receive as a screen for tuberculosis. 00:27:37.122 --> 00:27:42.594 In this case, what we're looking for is has the patient been exposed 00:27:42.794 --> 00:27:46.197 to Mycobacterium tuberculosis in some 00:27:47.198 --> 00:27:48.900 point in the past? 00:27:48.900 --> 00:27:52.170 If he has been exposed, he has memory T-cells 00:27:52.437 --> 00:27:55.507 which will be directed against that antigen. 00:27:56.107 --> 00:27:59.744 If a small amount of antigen is injected into the skin, 00:28:00.345 --> 00:28:05.583 if the patient has the memory T-cells, they will be recruited to the area. 00:28:05.984 --> 00:28:09.654 They will form an inflammatory response. 00:28:09.988 --> 00:28:15.160 And within a day or two, you'll see the raised area 00:28:15.160 --> 00:28:20.131 and the swelling and the redness of a positive TB skin. 00:28:20.131 --> 00:28:21.433 Test. 00:28:21.433 --> 00:28:26.604 In this case, though, they are injecting a purified protein derivative 00:28:26.604 --> 00:28:29.974 of the mycobacterium, so you're not really being 00:28:29.974 --> 00:28:33.044 exposed to the bacteria itself. 00:28:33.745 --> 00:28:36.314 And now there is a new test, 00:28:36.314 --> 00:28:40.118 a new screening test for tuberculosis that has been developed. 00:28:40.585 --> 00:28:43.822 It's an interferons gamma release assay. 00:28:44.355 --> 00:28:48.193 And many laboratories are using this as a screening test. 00:28:48.193 --> 00:28:51.196 It is a test that involves that 00:28:51.362 --> 00:28:53.932 occurs in the laboratory in a test tube. 00:28:55.867 --> 00:28:58.136 A positive tuberculosis skin test 00:28:58.136 --> 00:29:01.239 does not indicate that a patient has active 00:29:02.774 --> 00:29:04.142 tuberculosis going on. 00:29:04.142 --> 00:29:08.580 It just means that at some point in the past, they have been exposed 00:29:08.580 --> 00:29:11.583 to mycobacterium tuberculosis. 00:29:12.383 --> 00:29:15.687 If a positive skin test is discovered, 00:29:16.020 --> 00:29:20.024 usually the clinician will order a lung X-ray 00:29:20.191 --> 00:29:23.495 to really see if there is tuberculosis 00:29:23.795 --> 00:29:26.798 tuberculosis going on in the patient. 00:29:28.800 --> 00:29:31.803 As a review for hypersensitivity, 00:29:32.604 --> 00:29:35.073 you have a chart, 00:29:35.073 --> 00:29:37.275 and I would suggest 00:29:37.275 --> 00:29:40.278 that you go ahead and complete this chart. 00:29:42.280 --> 00:29:45.917 To help you study for any exams and to get the four types 00:29:45.917 --> 00:29:49.254 of hypersensitivity set in your mind. 00:29:51.756 --> 00:29:54.759 Just to get you started, 00:29:54.993 --> 00:29:57.362 let's do a little review. 00:29:57.362 --> 00:30:02.734 We've got three types of hypersensitivity that are involved with antibodies. 00:30:03.134 --> 00:30:07.972 Type four hypersensitivity is just cell mediated immunity. 00:30:08.907 --> 00:30:12.577 The basic mechanism of type one or immediate 00:30:12.577 --> 00:30:17.315 hypersensitivity is IgG coated mast cells 00:30:17.949 --> 00:30:21.119 and the release of mediators such as histamine 00:30:21.419 --> 00:30:25.757 that go out into the body trigger histamine receptor receptors, 00:30:26.057 --> 00:30:30.595 and you'll see the symptoms varying from hay fever to anaphylaxis. 00:30:31.563 --> 00:30:32.130 The basic 00:30:32.130 --> 00:30:36.935 mechanism of cytotoxic hypersensitivity is antigen 00:30:36.935 --> 00:30:40.471 on a cell surface membrane, and the immune cells. 00:30:40.839 --> 00:30:43.608 The immune response causes damage 00:30:43.608 --> 00:30:46.611 to the cell where that antigen is occurring. 00:30:46.911 --> 00:30:49.714 For example, a transfusion reaction 00:30:49.714 --> 00:30:52.717 or hemolytic disease of the newborn. 00:30:53.251 --> 00:30:55.186 Type three hypersensitivity. 00:30:55.186 --> 00:30:59.858 Its basic mechanism is small immune complexes 00:31:00.258 --> 00:31:03.027 where the antigen was soluble, 00:31:03.027 --> 00:31:05.797 and when it combines with antibody, 00:31:05.797 --> 00:31:09.901 the immune complexes settle in the tissue complement 00:31:09.901 --> 00:31:13.504 and neutrophils get recruited and cause tissue destruction. 00:31:14.806 --> 00:31:18.443 The basic mechanism of type four involves 00:31:18.443 --> 00:31:22.046 no antibody or complement, but it is cell mediated. 00:31:22.046 --> 00:31:25.250 Immunity and it's called delayed type 00:31:25.650 --> 00:31:29.587 because reactions usually occur only days 00:31:29.587 --> 00:31:32.590 after exposure to the allergen. 00:31:37.061 --> 00:31:38.162 Okay, it's 00:31:38.162 --> 00:31:42.000 now up to you to finish filling in this chart to help you 00:31:42.000 --> 00:31:45.503 in your review and studying for an exam. 00:31:45.870 --> 00:31:49.474 If you have any questions, you can consult your textbook, 00:31:49.841 --> 00:31:51.910 or you can ask your instructor. 00:31:53.745 --> 00:31:56.014 I thank you for your attention 00:31:56.014 --> 00:31:59.951 and I wish you the best of luck in studying for your exams.