WEBVTT 00:00:07.741 --> 00:00:09.709 Welcome, everybody. 00:00:09.709 --> 00:00:13.513 My name is Barbara Bunkie and I am an education 00:00:13.513 --> 00:00:17.584 coordinator in the Institute for Learning at Arup Laboratories. 00:00:18.051 --> 00:00:21.054 I'm a medical technologist by background 00:00:21.388 --> 00:00:24.391 and a specialist in immunology. 00:00:24.691 --> 00:00:27.961 I'm actually going to be giving two presentations. 00:00:28.395 --> 00:00:32.499 The one today will be on immediate hypersensitivity. 00:00:32.799 --> 00:00:35.802 The next session will be on 00:00:36.302 --> 00:00:39.339 types two, three and four hypersensitivity. 00:00:39.839 --> 00:00:42.475 To go along with this presentation today. 00:00:42.475 --> 00:00:47.747 You should have printed out the handouts that accompany the lecture. 00:00:47.781 --> 00:00:53.253 There's a lecture outline and a schematic 00:00:53.253 --> 00:00:56.589 or a diagram that you can follow along with. 00:00:57.924 --> 00:01:02.195 One of the first things when we talk about hypersensitivity is the question, 00:01:02.462 --> 00:01:05.565 what actually is hypersensitivity? 00:01:06.266 --> 00:01:08.601 Hypersensitivity by definition, 00:01:08.601 --> 00:01:12.072 is a heightened state of immune responsiveness. 00:01:13.006 --> 00:01:16.609 It's an exaggerated or inappropriate immune response 00:01:16.609 --> 00:01:19.612 which causes damage in a host. 00:01:19.646 --> 00:01:22.282 Note these are the same kind 00:01:22.282 --> 00:01:25.385 of immune responses that you'd see in a healthy person. 00:01:25.685 --> 00:01:29.889 They're the same mechanisms that the body uses when it fights off 00:01:30.156 --> 00:01:34.027 bacteria, viruses, other foreign organisms. 00:01:34.427 --> 00:01:38.998 But it becomes a hypersensitivity when the end result 00:01:38.998 --> 00:01:43.203 of that immune response is damage to the host. 00:01:43.503 --> 00:01:44.938 Damage to cells. 00:01:46.606 --> 00:01:48.441 Traditionally, allergy meant 00:01:48.441 --> 00:01:51.444 the same thing as hypersensitivity, 00:01:51.744 --> 00:01:57.717 but recently we recognize the term allergy to refer 00:01:57.717 --> 00:02:01.621 to a specific type of hypersensitivity, which is type 00:02:01.621 --> 00:02:04.691 one hypersensitivity and 00:02:05.825 --> 00:02:10.563 it's more the type of hypersensitivity when you talk like hay fever, 00:02:11.264 --> 00:02:14.701 allergies, allergic rhinitis, those kinds of things. 00:02:15.969 --> 00:02:18.238 So today we're going to talk about 00:02:18.238 --> 00:02:21.241 type one hypersensitivity. 00:02:21.608 --> 00:02:25.945 Back in 1962, two guys with the last names of J.L. 00:02:25.945 --> 00:02:28.982 and Coombs came up with a classification 00:02:28.982 --> 00:02:31.985 system of hypersensitivity. 00:02:32.552 --> 00:02:37.824 And they based classifications on the different basic 00:02:37.824 --> 00:02:41.828 mechanisms of immune injury that were occurring. 00:02:42.829 --> 00:02:45.865 They called them types one, two, three and four. 00:02:46.666 --> 00:02:48.601 Type one hypersensitivity. 00:02:48.601 --> 00:02:52.972 The one that we'll discuss today is immediate hypersensitivity 00:02:53.373 --> 00:02:57.177 because it can start occurring within seconds of exposure 00:02:57.177 --> 00:03:02.081 to the allergen, also called anaphylactic hypersensitivity. 00:03:02.715 --> 00:03:05.618 Type two is antibody dependent. 00:03:05.618 --> 00:03:10.623 Cytotoxic type three is immune complex hypersensitivity. 00:03:11.558 --> 00:03:16.396 Type four is a little bit different in that it is not antibody mediated. 00:03:16.696 --> 00:03:21.801 It's called cell mediated or delayed type hypersensitivity. 00:03:22.802 --> 00:03:24.270 Since we've come to 00:03:24.270 --> 00:03:27.273 know more about the immune system, 00:03:27.440 --> 00:03:32.111 these four classifications from Jill and Coombs have been modified somewhat. 00:03:32.946 --> 00:03:35.114 The four classifications 00:03:35.114 --> 00:03:38.151 are not completely separate from each other. 00:03:38.351 --> 00:03:40.820 Sometimes symptoms overlap. 00:03:40.820 --> 00:03:46.159 Sometimes they occur sequentially, but it's a lot easier to get them 00:03:46.159 --> 00:03:51.030 straight in your mind if you look at them as the four classifications. 00:03:51.764 --> 00:03:55.034 So type one hypersensitivity is called immediate. 00:03:56.002 --> 00:04:00.807 That's because reactions can begin within minutes of exposure 00:04:01.107 --> 00:04:05.011 to the antigen, which in this case we call an allergen. 00:04:05.812 --> 00:04:08.915 And like I mentioned earlier it includes hay fever, 00:04:08.915 --> 00:04:13.586 asthma hives and also anaphylactic 00:04:13.586 --> 00:04:18.224 shock is a type of hyper type one hypersensitivity. 00:04:18.725 --> 00:04:21.261 The reactions are dependent upon 00:04:21.261 --> 00:04:26.099 the triggering of I g e sensitized mast cells 00:04:26.099 --> 00:04:30.570 and base two fills, and then the release of the resulting 00:04:31.604 --> 00:04:33.973 inflammatory granules 00:04:33.973 --> 00:04:36.976 that come out from the mast cells and base of cells. 00:04:37.343 --> 00:04:41.047 So we have to understand what IGI is. 00:04:42.849 --> 00:04:44.517 You've studied the different kinds 00:04:44.517 --> 00:04:47.520 of antibodies, the different classifications. 00:04:47.920 --> 00:04:50.923 What do you remember about IGI? 00:04:51.357 --> 00:04:54.360 Anything. 00:04:54.427 --> 00:04:57.430 Does anybody remember anything about IGI? 00:04:58.364 --> 00:05:01.367 Is it a monomer, a dimer, or a pentimento? 00:05:03.803 --> 00:05:05.305 It's a monomer. 00:05:05.305 --> 00:05:08.174 It looks a lot like IgG. 00:05:08.174 --> 00:05:09.609 So it's a monomer. 00:05:09.609 --> 00:05:13.780 And you'll see it's got the same basic Y structure 00:05:13.780 --> 00:05:17.850 as you'd see in an IG molecule. 00:05:18.117 --> 00:05:21.788 The heavy chains in an example epsilon 00:05:22.689 --> 00:05:25.024 and the light chains could be either kappa 00:05:25.024 --> 00:05:28.027 or lambda. 00:05:28.061 --> 00:05:31.064 IGI does not cross the placenta. 00:05:31.497 --> 00:05:34.867 So if a mother has IGI antibodies, they're not going 00:05:34.867 --> 00:05:37.870 to, cross to the fetus. 00:05:37.870 --> 00:05:41.007 IGI does not activate complement. 00:05:42.008 --> 00:05:44.644 It does not cause agglutination. 00:05:44.644 --> 00:05:46.779 It does not act as an option in. 00:05:47.914 --> 00:05:50.350 And it's found in only trace 00:05:50.350 --> 00:05:54.087 amounts in the human blood, in serum 00:05:54.721 --> 00:06:01.327 or plasma, only 0.04% of the serum immunoglobulin 00:06:01.627 --> 00:06:04.630 is IGI class. 00:06:06.466 --> 00:06:10.136 IgG in the body is more in the body tissues. 00:06:10.670 --> 00:06:14.073 It's found attached to base of fills in the blood 00:06:14.507 --> 00:06:18.511 and mast cells throughout the body, in the bronchial areas, 00:06:18.511 --> 00:06:23.549 around the GI tract, in the skin and connective tissues in the rest 00:06:24.150 --> 00:06:27.787 respiratory mucosa, and areas like that. 00:06:28.721 --> 00:06:31.290 Your overall scheme of type one 00:06:31.290 --> 00:06:34.293 hypersensitivity is seen on the diagram. 00:06:34.460 --> 00:06:41.200 And I'm going to talk about the three phases of type one hypersensitivity. 00:06:41.434 --> 00:06:44.437 We'll go into each of those in detail. 00:06:44.470 --> 00:06:48.908 The first phase of type one hypersensitivity is called 00:06:48.908 --> 00:06:51.377 the sensitization phase. 00:06:51.377 --> 00:06:55.815 This is the primary response when a person is first 00:06:55.815 --> 00:07:00.420 exposed to an antigen or the allergen. 00:07:00.953 --> 00:07:03.489 In most cases, it's a small protein. 00:07:04.624 --> 00:07:05.892 What happens is the 00:07:05.892 --> 00:07:10.296 antigen presenting cells process and present 00:07:10.296 --> 00:07:13.299 that allergen to the lymphocytes, 00:07:13.800 --> 00:07:16.803 the B cells and the T cells. 00:07:17.570 --> 00:07:19.739 T cells will provide 00:07:19.739 --> 00:07:22.975 help to the B cells to help them produce antibodies, 00:07:23.409 --> 00:07:26.846 especially the T two helper 00:07:26.846 --> 00:07:30.383 cells are involved and they will produce 00:07:30.883 --> 00:07:33.519 an interleukin called interleukin four, 00:07:33.519 --> 00:07:36.556 which specifically helps the B cells 00:07:37.256 --> 00:07:40.293 make IgG type antibody. 00:07:41.260 --> 00:07:43.563 There's a genetic tendency 00:07:43.563 --> 00:07:46.666 for, an individual to do this. 00:07:47.433 --> 00:07:51.971 The IG then is quickly it goes into the bloodstream. 00:07:51.971 --> 00:07:56.642 It goes through the tissue and attached tightly to the mast cells. 00:07:56.642 --> 00:07:59.645 And the base of fills throughout the body. 00:08:00.847 --> 00:08:02.348 The IG half life 00:08:02.348 --> 00:08:05.785 on mast cells and base of cells is about ten days. 00:08:06.052 --> 00:08:08.821 Where in the bloodstream floating free. 00:08:08.821 --> 00:08:11.457 It would just be a couple of days. 00:08:11.457 --> 00:08:14.126 So now your mast cells and base of cells 00:08:14.126 --> 00:08:17.129 are called sensitized 00:08:17.163 --> 00:08:20.766 because they have IgG molecules on them 00:08:21.000 --> 00:08:26.973 that have been developed as the antigen presenting cells having seen the allergen. 00:08:27.540 --> 00:08:30.543 So you've got mast cells and base officials now sitting around 00:08:30.676 --> 00:08:33.346 that just have IgG attached to them. 00:08:34.747 --> 00:08:36.816 The second phase of 00:08:36.816 --> 00:08:39.819 type one hypersensitivity is the activation phase. 00:08:40.119 --> 00:08:43.656 This is on second exposure to the allergen. 00:08:45.391 --> 00:08:48.628 The IgG molecules, if they're close together 00:08:48.628 --> 00:08:52.231 on the mast cells the antigen can cross link them. 00:08:52.231 --> 00:08:56.903 And this triggers changes in the cell membrane of the mast cell. 00:08:58.271 --> 00:09:01.140 There is a calcium influx 00:09:01.140 --> 00:09:04.143 that goes into the cell 00:09:04.410 --> 00:09:07.880 and there is a triggering 00:09:07.880 --> 00:09:11.717 for granulation of the mast cell. 00:09:12.051 --> 00:09:16.489 So any of the granules that have been contained inside the cell 00:09:16.722 --> 00:09:19.725 now get released out into the environment. 00:09:20.326 --> 00:09:23.095 These granules are called mediators. 00:09:23.095 --> 00:09:26.098 Mediators of type one hypersensitivity. 00:09:27.800 --> 00:09:30.803 The third phase is called the effector phase. 00:09:31.170 --> 00:09:35.441 This is when the mediators travel throughout the tissue and the bloodstream, 00:09:35.775 --> 00:09:38.544 and they reach their effector sites, 00:09:38.544 --> 00:09:42.114 and they attach to receptors throughout the body. 00:09:43.015 --> 00:09:46.118 And those receptors could be in the bronchioles. 00:09:46.452 --> 00:09:48.821 They could be in the blood vessels. 00:09:48.821 --> 00:09:50.356 Could be in smooth muscle. 00:09:50.356 --> 00:09:51.757 Could be in your skin. 00:09:52.925 --> 00:09:55.861 And the symptoms of 00:09:55.861 --> 00:09:58.965 asthma, allergies, hay fever, 00:09:59.332 --> 00:10:02.435 anaphylaxis are what now occurs. 00:10:03.135 --> 00:10:06.973 So when those mediators go out and they reach their receptors 00:10:06.973 --> 00:10:11.577 throughout the body, that's when you get the symptoms of hypersensitivity. 00:10:12.244 --> 00:10:16.682 Preformed mediators are those that are immediately available 00:10:17.149 --> 00:10:20.853 in the cell membrane of the mast cell or base in film. 00:10:21.587 --> 00:10:24.790 It takes just seconds for these to be released 00:10:24.790 --> 00:10:28.561 after those IgG antibodies have become cross-linked. 00:10:28.995 --> 00:10:31.998 Histamine is probably the most important one. 00:10:33.633 --> 00:10:35.501 Cells for 00:10:35.501 --> 00:10:40.406 cells that have receptors for histamine will respond within just a few seconds, 00:10:40.773 --> 00:10:44.910 and the response could last maybe 10 to 30 minutes or so. 00:10:45.544 --> 00:10:48.247 Histamine causes, 00:10:48.247 --> 00:10:50.182 a whole group 00:10:50.182 --> 00:10:54.253 of symptoms to occur smooth muscle contraction 00:10:54.253 --> 00:10:58.157 in the bronchioles and the blood vessels and the intestines. 00:10:58.691 --> 00:11:01.494 So you would see airflow obstruction. 00:11:01.494 --> 00:11:04.497 You would see cramps. You would see, 00:11:05.464 --> 00:11:08.334 the the stomach problems that you would get 00:11:08.334 --> 00:11:11.537 when someone says, I have an allergy to that kind of food. 00:11:12.471 --> 00:11:16.142 You'll see increased, capillary permeability 00:11:17.043 --> 00:11:19.545 caused by the, 00:11:19.545 --> 00:11:22.548 histamine receptors in the bloodstream. 00:11:22.682 --> 00:11:28.487 This causes fluid to be able to released, be released from your capillaries 00:11:28.487 --> 00:11:32.892 into the tissue, and you can get mediators out into the tissue. 00:11:32.925 --> 00:11:34.794 You can get edema. 00:11:34.794 --> 00:11:37.797 You can get swelling because of that. 00:11:39.098 --> 00:11:40.566 Histamine also causes 00:11:40.566 --> 00:11:43.569 increased mucus production. 00:11:43.936 --> 00:11:46.505 Watery eyes, runny nose. 00:11:46.505 --> 00:11:49.141 The symptoms like that. 00:11:49.141 --> 00:11:50.976 And then you'd also see 00:11:50.976 --> 00:11:53.979 local erythema or redness. 00:11:55.147 --> 00:11:58.384 A second preform mediator is eosinophil 00:11:58.584 --> 00:12:03.556 chemo tactic factor of anaphylaxis or ECF a 00:12:04.156 --> 00:12:06.792 it attracts eosinophilic to the area. 00:12:06.792 --> 00:12:09.795 Eosinophilic are white blood cells 00:12:10.029 --> 00:12:14.133 that are really important in fighting parasitic worm infections. 00:12:14.967 --> 00:12:17.970 The eosinophils in turn can release granules, 00:12:17.970 --> 00:12:21.474 which dampen the effects of histamine and other granules 00:12:21.741 --> 00:12:26.612 so they can cause a downregulation of this type one hypersensitivity. 00:12:27.513 --> 00:12:29.749 Neutrophil chemo tactic 00:12:29.749 --> 00:12:33.285 factor attracts neutrophils to the area. 00:12:33.285 --> 00:12:36.622 These are other white blood cells that fight off infection 00:12:37.723 --> 00:12:39.091 and proteolytic 00:12:39.091 --> 00:12:42.595 enzymes such as trip tapes and kinase, 00:12:43.095 --> 00:12:46.665 which could help destroy the allergen. 00:12:47.399 --> 00:12:50.302 Newly synthesized mediators 00:12:50.302 --> 00:12:53.372 developed sometime after the initial event, 00:12:53.372 --> 00:12:56.575 and they prolong the hypersensitivity consequences 00:12:56.942 --> 00:13:00.679 to 6 to 8 hours after initial exposure 00:13:01.213 --> 00:13:05.050 to the allergen, and they develop from the Mem, 00:13:05.050 --> 00:13:09.789 the cell membrane lipids of the base of cells and the mast cells. 00:13:10.623 --> 00:13:13.659 So some examples of these are prostaglandins, 00:13:14.460 --> 00:13:17.463 which mimic the effects of histamine 00:13:18.898 --> 00:13:20.966 leukotrienes. 00:13:20.966 --> 00:13:24.436 An important one here is called slow reacting 00:13:24.436 --> 00:13:28.174 substance of anaphylaxis which is very potent. 00:13:28.507 --> 00:13:32.278 It's 100 times stronger than histamine. 00:13:34.580 --> 00:13:36.749 And platelet activating factor 00:13:36.749 --> 00:13:39.618 which causes platelet aggregation, 00:13:39.618 --> 00:13:42.621 promotes inflammation. 00:13:42.655 --> 00:13:46.826 Vasodilation, and production of rapid shock syndrome. 00:13:47.860 --> 00:13:51.163 Some of the clinical events that you would see in a type one 00:13:51.497 --> 00:13:54.600 hypersensitivity ATP 00:13:55.000 --> 00:13:57.870 is one that we hear about. 00:13:58.971 --> 00:14:02.174 ATP is a predisposition towards 00:14:02.174 --> 00:14:05.177 developing allergies or type one 00:14:05.311 --> 00:14:08.247 hypersensitivity. 00:14:08.247 --> 00:14:10.683 ATP is a state of predisposition 00:14:10.683 --> 00:14:13.886 towards developing allergies such as hay fever, 00:14:14.987 --> 00:14:17.089 allergy to pollens, animals. 00:14:17.089 --> 00:14:20.092 Dust mites. Some types of asthma. 00:14:20.326 --> 00:14:24.029 About 10% of the population has ATP. 00:14:24.630 --> 00:14:28.701 This predisposition is inherited. 00:14:29.468 --> 00:14:32.471 A child of one atopic parent 00:14:32.538 --> 00:14:35.774 has a 50% chance of developing allergies. 00:14:36.141 --> 00:14:40.412 And if both of your parents are atopic, 00:14:40.412 --> 00:14:45.317 there's a 75% chance that the child will also develop allergies. 00:14:46.051 --> 00:14:48.454 Note those allergies 00:14:48.454 --> 00:14:51.457 may not be to the exact same things. 00:14:51.824 --> 00:14:56.996 So if your parent has an allergy to sagebrush or strawberries, 00:14:56.996 --> 00:15:00.633 it doesn't necessarily mean you'll have those same allergies, 00:15:01.000 --> 00:15:03.636 but it shows that you're going to have a tendency 00:15:03.636 --> 00:15:06.639 to develop allergies. 00:15:06.805 --> 00:15:09.341 Asthma is 00:15:09.341 --> 00:15:13.812 when allergic particles reach the lower 00:15:13.812 --> 00:15:16.949 respiratory tract in your system. 00:15:17.750 --> 00:15:20.152 And so instead of 00:15:21.453 --> 00:15:22.087 hay fever, 00:15:22.087 --> 00:15:26.125 watery eyes, runny nose, you get the airflow obstruction 00:15:26.125 --> 00:15:31.563 and difficulty breathing because of bronchial muscle contraction. 00:15:31.897 --> 00:15:35.200 Mucus in the lungs and trapped air. 00:15:37.069 --> 00:15:39.305 A common problem 00:15:39.305 --> 00:15:43.008 to an inhaled allergen in an ectopic 00:15:43.008 --> 00:15:46.011 individual is allergic rhinitis, 00:15:46.712 --> 00:15:49.381 which is the runny nose, 00:15:49.381 --> 00:15:51.684 and we see it a lot as hay fever. 00:15:51.684 --> 00:15:57.122 Here to go along with the runny nose, there are watery eyes, nasal stuffiness. 00:15:57.990 --> 00:16:01.593 The symptoms of allergic rhinitis are annoying 00:16:03.228 --> 00:16:07.132 at best, but they can lead to serious complications 00:16:07.132 --> 00:16:11.303 like ear infections, sinusitis and other conditions 00:16:11.303 --> 00:16:14.306 like that. 00:16:14.306 --> 00:16:16.508 So just a word about 00:16:16.508 --> 00:16:19.511 inheritance of allergies. 00:16:19.578 --> 00:16:21.947 There are several theories as to 00:16:21.947 --> 00:16:24.950 how ATP is inherited. 00:16:25.451 --> 00:16:28.454 And one of those theories says that 00:16:29.088 --> 00:16:32.624 you have a tendency to overproduce 00:16:32.624 --> 00:16:35.627 IgG antibodies. 00:16:36.362 --> 00:16:38.864 The tendency may be, 00:16:38.864 --> 00:16:43.435 inherited as a recessive trait in some individuals. 00:16:43.836 --> 00:16:47.606 Perhaps there's an HLA linked tendency. 00:16:47.906 --> 00:16:51.310 It's looking more and like certain HLA types 00:16:51.310 --> 00:16:56.015 in individuals, are more likely to make the strong 00:16:56.015 --> 00:17:00.986 affinity receptors on your base of fills and your mast cells. 00:17:01.186 --> 00:17:05.858 So if you've inherited that tendency to really strongly grab on to IgG 00:17:05.891 --> 00:17:09.862 molecules, you're going to be more likely to develop allergies. 00:17:11.163 --> 00:17:14.967 Another factor may be a tendency to produce 00:17:15.300 --> 00:17:18.537 low IgG antibodies. 00:17:18.904 --> 00:17:22.841 IGA antibodies are the class that you would see in your secretions. 00:17:23.409 --> 00:17:26.612 And if you have fewer IgG antibodies, 00:17:26.912 --> 00:17:29.882 that allows allergens to get into your system 00:17:30.049 --> 00:17:33.819 and get exposed to those sensitized mast cells and basic cells. 00:17:34.353 --> 00:17:37.022 So if you don't have the immediate line of defense, 00:17:37.022 --> 00:17:41.827 then you're more likely to develop an IGA reaction. 00:17:42.561 --> 00:17:45.931 Also, decreased T suppressor cells. 00:17:47.032 --> 00:17:52.037 The control of producing IgG antibodies 00:17:52.037 --> 00:17:57.209 is actually held under suppression by the T suppressor cells. 00:17:57.409 --> 00:18:00.946 So if you don't have as many of those, your cells 00:18:00.946 --> 00:18:03.949 are more likely to continue producing the IgG. 00:18:06.085 --> 00:18:09.688 So let's talk a little bit about food allergies. 00:18:09.955 --> 00:18:12.958 This happens when the allergen is ingested. 00:18:13.525 --> 00:18:16.395 Some of the most common food allergies 00:18:16.395 --> 00:18:20.332 involve cows milk, peanuts, and eggs 00:18:22.034 --> 00:18:23.769 certain shellfish. 00:18:23.769 --> 00:18:27.706 And there are several things that can cause allergies. 00:18:28.340 --> 00:18:29.708 Food allergies. 00:18:29.708 --> 00:18:33.645 If the symptoms are just occurring in the digestive tract, 00:18:34.046 --> 00:18:38.550 the person might experience cramps, diarrhea, vomiting, 00:18:39.284 --> 00:18:42.287 those kinds of things. 00:18:42.387 --> 00:18:44.456 However, the mediators 00:18:44.456 --> 00:18:48.794 can also cause a change in stomach permeability, and the allergen 00:18:48.794 --> 00:18:52.297 can go through the stomach and small intestines into the body. 00:18:53.232 --> 00:18:56.635 And when those allergens now get into your bloodstream, 00:18:57.202 --> 00:19:00.205 you might see hives or eczema 00:19:00.572 --> 00:19:03.609 occurring because of the food that was consumed. 00:19:04.076 --> 00:19:08.280 Or in the worst case scenario, you'd see anaphylactic shock. 00:19:08.714 --> 00:19:11.517 And that's when the allergen goes 00:19:11.517 --> 00:19:14.286 throughout the body. 00:19:14.286 --> 00:19:17.256 The localized skin reaction 00:19:17.256 --> 00:19:21.760 is called urticaria or hives that were 00:19:22.027 --> 00:19:25.531 those are the terms that we're familiar with in the lab. 00:19:25.664 --> 00:19:29.401 We often call it the heel and flare reaction. 00:19:30.102 --> 00:19:32.437 And it's the large 00:19:33.438 --> 00:19:34.973 red bump 00:19:34.973 --> 00:19:39.111 or large red bumps that you would see in an allergy. 00:19:39.945 --> 00:19:43.215 Anaphylaxis is the most severe 00:19:43.215 --> 00:19:46.218 kind of allergic reaction that you can see. 00:19:46.585 --> 00:19:51.790 It's a systemic reaction when mast cells throughout the body are triggered 00:19:52.024 --> 00:19:56.595 and there's a massive release of histamine and other mediators. 00:19:56.828 --> 00:19:59.831 The allergen is 00:19:59.998 --> 00:20:02.067 usually ingested 00:20:02.067 --> 00:20:05.070 or it gets directly into the bloodstream. 00:20:05.871 --> 00:20:08.874 Common culprits here could be bee venom, 00:20:09.541 --> 00:20:12.511 a drug like penicillin, 00:20:12.644 --> 00:20:15.781 and foods such as nuts, seafood, 00:20:17.082 --> 00:20:19.718 latex, things like that. 00:20:19.718 --> 00:20:24.089 The vascular permeability throughout the whole body is affected, 00:20:24.356 --> 00:20:27.859 so the symptoms may start as hives or cramps, 00:20:28.393 --> 00:20:33.332 but they can proceed to shock or death as the vessels dilate. 00:20:34.066 --> 00:20:36.501 Fluids leave the bloodstream. 00:20:36.501 --> 00:20:38.470 Tissue edema occurs. 00:20:38.470 --> 00:20:40.505 Blood flow slows. 00:20:40.505 --> 00:20:43.242 Blood pressure drops. 00:20:43.242 --> 00:20:46.078 The bronchioles become constricted. 00:20:46.078 --> 00:20:49.548 Often a person who is having an anaphylactic reaction. 00:20:50.282 --> 00:20:53.518 Their reaction is to grab their neck 00:20:53.652 --> 00:20:58.390 because they are unable to get enough air because of the swelling. 00:20:58.890 --> 00:21:02.361 And a person in anaphylactic shock can actually die 00:21:02.361 --> 00:21:06.865 of drowning from the fluids that are accumulating in his lungs. 00:21:08.567 --> 00:21:10.135 So it's life threatening. 00:21:10.135 --> 00:21:13.338 So how do we diagnose type one hypersensitivity? 00:21:15.173 --> 00:21:18.810 Well, first of all, we do need to establish that IgG 00:21:19.077 --> 00:21:22.714 mechanisms are the cause of the symptoms. 00:21:23.348 --> 00:21:27.019 And we need to find out what the allergen is, what the trigger is. 00:21:27.219 --> 00:21:30.789 So we look at the clinical picture of the patient. 00:21:31.156 --> 00:21:33.358 We look at the family history. 00:21:33.358 --> 00:21:36.128 We look is there a seasonal incidence 00:21:36.128 --> 00:21:39.131 to the allergic reaction. 00:21:39.798 --> 00:21:42.301 Blood work performed on the patient 00:21:42.301 --> 00:21:46.271 may show an increased serum level of IGI 00:21:46.872 --> 00:21:51.543 and eosinophilia, high levels of eosinophilia, but not always. 00:21:52.144 --> 00:21:54.880 Okay, so the clinical picture 00:21:54.880 --> 00:21:56.581 in vivo skin tests. 00:21:56.581 --> 00:21:58.517 You've probably heard of those. 00:21:58.517 --> 00:22:01.119 Some of you may have actually had a skin test. 00:22:01.119 --> 00:22:04.122 They're called a prick test or 00:22:05.791 --> 00:22:08.226 another kind of, skin test. 00:22:08.226 --> 00:22:11.229 They can be done on your arm or on your back. 00:22:11.363 --> 00:22:14.132 What happens in those testing is 00:22:15.200 --> 00:22:17.769 there's actually a mini allergic reaction 00:22:17.769 --> 00:22:20.772 that is trying to be produced on your body. 00:22:20.806 --> 00:22:23.308 The clinician will inject tiny amounts 00:22:23.308 --> 00:22:27.412 of various kinds of allergens into your skin, and then wait 00:22:27.412 --> 00:22:30.682 and see if an allergic reaction occurs in your skin. 00:22:31.650 --> 00:22:34.786 Many, many allergic reaction will occur 00:22:34.786 --> 00:22:38.623 within 15 minutes of having the exposure. 00:22:39.858 --> 00:22:42.861 It's relatively simple to do. 00:22:43.095 --> 00:22:45.964 Relatively inexpensive to do, 00:22:45.964 --> 00:22:49.134 but certainly not a desirable thing to do. 00:22:49.568 --> 00:22:54.106 If any of you have ever had any, allergy skin prick test, 00:22:54.506 --> 00:22:58.210 you could attest to the fact that it's not very pleasant, 00:22:58.477 --> 00:23:02.114 but it is a very good way to diagnose 00:23:02.114 --> 00:23:05.117 what a person's allergic to. 00:23:06.151 --> 00:23:08.153 Diagnosis of type 00:23:08.153 --> 00:23:11.857 one hypersensitivity is also done by 00:23:11.857 --> 00:23:15.594 measuring IgG levels in the bloodstream. 00:23:16.094 --> 00:23:19.097 We can measure total IgG level 00:23:19.264 --> 00:23:23.535 or allergen specific IGI levels. 00:23:24.069 --> 00:23:28.440 The total IgG level has traditionally been called the wrist 00:23:28.840 --> 00:23:31.843 or the radio immunosorbent test. 00:23:32.411 --> 00:23:36.248 And traditionally, the allergen specific 00:23:36.481 --> 00:23:39.551 IgG testing has been called Rast or 00:23:39.818 --> 00:23:42.821 radio allergic or sorbent testing. 00:23:42.954 --> 00:23:46.591 Now we don't use radioactivity as a laboratory 00:23:48.059 --> 00:23:49.995 technology much anymore. 00:23:49.995 --> 00:23:54.933 So both of these testing are done by enzyme 00:23:54.933 --> 00:23:57.936 immunoassays or 00:23:58.804 --> 00:24:02.174 or FDA fluorescent enzyme 00:24:02.174 --> 00:24:06.411 immunoassays, or by karma luminescent assays. 00:24:06.611 --> 00:24:10.248 But the traditional terms still stick. 00:24:13.685 --> 00:24:17.155 Therapy for type one hypersensitivity. 00:24:17.389 --> 00:24:19.724 Number one avoidance. 00:24:19.724 --> 00:24:24.029 Stay away from or don't eat the offending antigen. 00:24:24.429 --> 00:24:26.998 The whole lot easier for foods to avoid. 00:24:26.998 --> 00:24:28.500 Foods. 00:24:28.500 --> 00:24:31.503 If you're allergic to 00:24:31.503 --> 00:24:32.838 sagebrush. 00:24:32.838 --> 00:24:35.841 I would say don't breathe. 00:24:36.074 --> 00:24:40.145 Yeah, or don't live in an area where sagebrush is common. 00:24:40.145 --> 00:24:42.380 If you're allergic to cats, probably it wouldn't 00:24:42.380 --> 00:24:45.584 be a good idea to have cats as a pet. 00:24:46.117 --> 00:24:48.587 But sometimes a person is unable 00:24:48.587 --> 00:24:51.823 to avoid the things that they have allergies to. 00:24:52.491 --> 00:24:57.529 In this case, there is a therapy that's called hypo sensitization. 00:24:58.163 --> 00:25:02.400 And what you do is you give the patient a series of shots or injections 00:25:02.667 --> 00:25:05.670 with tiny amounts of the allergen, 00:25:05.670 --> 00:25:10.442 the antigen, and you give increasing doses to the patient, 00:25:11.042 --> 00:25:14.880 and they build a sort of tolerance towards the allergen. 00:25:15.614 --> 00:25:18.950 The goal here is to help the patient 00:25:18.950 --> 00:25:22.921 develop high levels of the IgG type antibody, 00:25:23.421 --> 00:25:26.825 so that if the patient is exposed to the allergen, 00:25:27.158 --> 00:25:31.129 their IG will grab on and take care of the allergen 00:25:31.396 --> 00:25:35.700 before they can get to the sensitized mast cells or patient cells. 00:25:36.268 --> 00:25:39.704 This has been pretty effective for like bee stings 00:25:40.171 --> 00:25:42.941 and certain inhaled allergies. 00:25:45.710 --> 00:25:47.679 Also, drugs and medications 00:25:47.679 --> 00:25:51.283 can be used to treat allergy symptoms. 00:25:51.650 --> 00:25:55.287 The most important one, or the most common one is antihistamines. 00:25:56.488 --> 00:25:58.890 Antihistamines compete with histamine 00:25:58.890 --> 00:26:01.860 for the receptors in in the tissue, 00:26:02.093 --> 00:26:06.097 so they block the effects of histamine when it is produced. 00:26:06.998 --> 00:26:11.102 Often works in symptoms of, hay fever. 00:26:12.437 --> 00:26:15.073 A problem with antihistamines 00:26:15.073 --> 00:26:18.076 is especially the first generation ones. 00:26:18.109 --> 00:26:20.378 They also 00:26:20.378 --> 00:26:23.381 cause drowsiness in the patient. 00:26:23.548 --> 00:26:28.653 So the same mechanisms that were blocking the histamine were causing drowsiness. 00:26:29.054 --> 00:26:32.057 There are now better anti anti. 00:26:32.390 --> 00:26:35.527 There are now better antihistamines that don't 00:26:35.527 --> 00:26:38.530 cause the drowsiness problems. 00:26:39.297 --> 00:26:42.300 Epinephrine or adrenaline. 00:26:43.401 --> 00:26:46.905 Epinephrine is the lifesaving therapy. 00:26:47.172 --> 00:26:50.175 If a person has gone into anaphylactic shock 00:26:50.775 --> 00:26:55.647 it's the EpiPen that you hear about that some people who are really allergic 00:26:55.647 --> 00:26:59.317 to peanuts or bee stings carry around with them. 00:27:00.151 --> 00:27:04.823 It relaxes smooth muscle and it decreases capillary permeability. 00:27:05.824 --> 00:27:07.993 Some others are 00:27:07.993 --> 00:27:11.863 bronchodilators, such as the offline, which are useful in asthma. 00:27:12.564 --> 00:27:18.336 Steroid hormones which reduce inflammation, and recombinant 00:27:18.336 --> 00:27:21.339 IG antibody therapy. 00:27:22.240 --> 00:27:25.910 So a summary for type one hypersensitivity. 00:27:26.711 --> 00:27:29.080 We've talked about 00:27:29.080 --> 00:27:31.383 immediate hypersensitivity. 00:27:31.383 --> 00:27:33.952 Type one is called immediate because it can occur 00:27:33.952 --> 00:27:38.256 within seconds or minutes after exposure to the allergen. 00:27:38.256 --> 00:27:41.259 And the culprit antibody is IgG. 00:27:42.594 --> 00:27:45.630 There are three phases to type one 00:27:45.630 --> 00:27:49.467 hypersensitivity sensitization, which is primary 00:27:49.467 --> 00:27:52.470 exposure to the allergen 00:27:52.671 --> 00:27:54.139 activation. 00:27:54.139 --> 00:27:57.442 When the allergen is encountered a second time, 00:27:57.976 --> 00:28:02.514 and the mast cells and base of fills are triggered to release their granules. 00:28:03.248 --> 00:28:04.683 The effector phase. 00:28:04.683 --> 00:28:09.587 When the histamine and other mediators go out into the tissue 00:28:09.854 --> 00:28:12.857 and cause their responses, 00:28:14.125 --> 00:28:16.961 the mediators are preformed 00:28:16.961 --> 00:28:20.732 or newly synthesized out of the mast cells and base fills. 00:28:21.032 --> 00:28:23.401 Most important, one histamine. 00:28:23.401 --> 00:28:27.205 But you'll also see other mediators that attract eosinophilia, 00:28:27.539 --> 00:28:30.775 platelets, and other white blood cells. 00:28:31.676 --> 00:28:35.580 Some of the common clinical events that you would see are ATP, 00:28:36.915 --> 00:28:38.316 food allergies 00:28:38.316 --> 00:28:41.319 and in a serious case, anaphylaxis. 00:28:42.120 --> 00:28:44.155 Diagnosis of type 00:28:44.155 --> 00:28:48.727 one hypersensitivity is to find out. 00:28:48.727 --> 00:28:51.663 First of all, does the patient have an allergy? 00:28:51.663 --> 00:28:54.399 What's the clinical picture? 00:28:54.399 --> 00:28:57.268 Do they have a high level of IgG 00:28:57.268 --> 00:29:00.672 antibodies by the wrist test? 00:29:01.873 --> 00:29:05.009 Do they have high levels of specific 00:29:05.343 --> 00:29:09.814 IgG antibodies against specific allergens, 00:29:10.048 --> 00:29:13.051 which is called the Rast test? 00:29:13.852 --> 00:29:17.155 Therapies for type one hypersensitivity 00:29:17.422 --> 00:29:20.425 can include avoidance of the allergen, 00:29:21.760 --> 00:29:24.763 hypo sensitization, injections, 00:29:25.029 --> 00:29:27.532 and various medications. 00:29:27.532 --> 00:29:32.637 A question that's been asked is since IGA is such a nuisance antibody, 00:29:32.871 --> 00:29:37.542 why in the world in the evolutionary process of human beings, 00:29:37.909 --> 00:29:41.479 did people develop high levels of IgG? 00:29:42.747 --> 00:29:45.283 And one of the theories is 00:29:45.283 --> 00:29:49.120 or one of the correlations that you find is in areas 00:29:49.120 --> 00:29:52.257 where there are lots of parasitic worm infections, 00:29:52.590 --> 00:29:55.460 there are very few allergies. 00:29:55.460 --> 00:30:00.231 It's only in civilized countries where we have cleared out, 00:30:01.499 --> 00:30:02.167 the various 00:30:02.167 --> 00:30:05.170 kinds of parasites that we are troubled 00:30:05.203 --> 00:30:08.206 by hay fever and asthma, 00:30:08.573 --> 00:30:11.576 because in parasitic communities, 00:30:11.943 --> 00:30:16.481 all of that IgG is on the mast, cells fighting off the schist 00:30:16.548 --> 00:30:19.784 dissolves, and all of the other worms. 00:30:20.819 --> 00:30:24.122 So I think it's just kind of interesting that we're being plagued 00:30:24.122 --> 00:30:29.861 by an evolutionary process that helps us fight parasitic worm infections. 00:30:30.361 --> 00:30:33.331 Thank you for your attention today. 00:30:33.364 --> 00:30:37.735 The second lecture in this series will be on types 00:30:37.735 --> 00:30:43.374 two, three and four hypersensitivity, and you will find a second lecture 00:30:43.374 --> 00:30:47.478 outline and handouts to go along with that presentation. 00:30:48.079 --> 00:30:49.047 Again thank you.