Type II Hypersensitivity: Examples

00:00 The good example of this is Goodpasture's disease, which is shown here.

00:05 In that case, the host who has developed Goodpasture's has developed auto antibodies that recognise components of the basement membrane in both lungs and in the kidney glomeruli.

00:18 And that's what we're looking at.

00:19 We're basically looking at a capillary loop on the left hand side, and a basement membrane to which antibodies have bound.

00:27 You can see them there, the little green guys.

00:29 And we are going to now recruit neutrophils, recruit complement, recruits macrophages, that will try to eat that and all they're going to end up doing is destroying the basement membrane.

00:41 And then we will have a filtration process that doesn't work.

00:44 That's Goodpasture's disease.

00:46 The figure on the right hand side is just demonstrating an immunofluorescence pattern for bound antibody, in that glomerulus.

00:57 So all those little tiny loops and things like that, we're just highlighting the capillaries that the antibody has bound to.

01:04 And you can see that there would be substantial damage, and why now that would destroy the filtration process in the kidney.

01:11 That's Goodpasture's disease.

01:14 Another example of antibody against fixed tissue antigen, this time on the heart.

01:19 And this is a good example.

01:20 This is acute rheumatic fever.

01:22 So if you've had a strep throat, streptococcal pharyngitis.

01:27 You elaborate antibodies against the group A streptococci.

01:31 That's what's being shown and that's an appropriate response.

01:35 Unfortunately, in some of the cases, the antibodies that are formed against the streptococcal antigens, cross react with similar not identical, but similar protein confirmations on the surface of the myocytes and on the valves.

01:53 Oh, my goodness.

01:54 Now I have antibodies bound to myocardium or bound valves, and it's predictable what's going to happen.

02:02 We're going to recruit and activate neutrophils and macrophages and Fc receptors, we're going to have complement activation, we're going to be punching holes, we're going to get major damage.

02:12 And that's exactly what happens in acute rheumatic fever.

02:15 In a small set of sub subset of patients who develop these antibodies, they do happen to cross react with self antigens.

02:22 And this is just showing you an example of what this looks like.

02:25 So we have now antibody that's bound to the myocardium and it is causing the recruitment and activation of T cells and macrophages to form a so called Aschoff nodule.

02:38 So the larger pinker cells in the panel on the left are macrophages that have bound up.

02:45 And all this is happening because of cross reactivity between the streptococcal organism and antigens present on the heart.

02:55 When it happens on the valves, we will cause inflammation, damage, and destruction.

03:01 As that heals, we'll get scarring.

03:04 And you can see on the left hand side, thickening of the mitral valve in a patient who had multiple bouts of rheumatic fever over the lifetime.

03:13 As a result, it have damaged that valve to the point where it's no longer pliable, and soft, but rather fibrotic and scarred, and doesn't function very well as a valve.

03:23 Again, Type 2 hypersensitivity response.

03:28 Another way to have a type two hypersensitivity response, in this case, without much associated inflammation or damage is shown here with Pemphigus Vulgaris.

03:40 These in people who have this disorder, they have auto antibodies that recognise desmosomal components.

03:48 So the dark black things in the middle panel are desmosomes that hold the keratinocytes together.

03:56 You can develop antibodies to those desmosomal proteins.

04:02 And when that happens, and you bind and crosslink them, you induce the production of urokinase plasminogen activator, that will cause a breakdown of those desmosomal proteins.

04:15 And you will therefore get separation of the keratinocytes.

04:20 And you get a characteristic blistering that happens at a certain level within the skin.

04:28 And this is just showing you that pattern.

04:30 The characteristic area for pemphigus vulgaris is at the cells at the basal layer.

04:37 So it's a very specific region with specific desmosomes that are being recognised and you get one basal layer stuck to the dermis, and then you have a blister above that because we broken all the desmosomes that connected the basil layer to the next layer up.

04:53 And it's not happening because of complement activation.

04:58 It's not happening because of macrophages and neutrophils coming in.

05:02 It's happening because of the activation of the plasminogen activator.

05:08 So you see the blister on the right hand side in the upper corner, you're also seeing the immunoglobulin deposition pattern.

05:15 So you get a lace like deposition of immunoglobulin on this immunofluorescence panel on the lower right, that shows where the antibody is being bound.

05:24 Grossly, what does this look like, areas of ulceration and blistering.

05:32 You can also have antibodies that bind to fixed antigen that don't drive any form of injury.

05:39 That in fact, act like stimulating molecules, or blocking molecules.

05:46 In this particular case, on the left hand side, we're showing antibodies that are directed against the thyroid stimulating hormone receptor, the TSH receptor.

05:55 Those antibodies when they buy the TSH receptor, stimulate the thyroidal cells.

06:01 So the patient, or the thyroid in this case, thinks it's been stimulated with a bunch of TSH when in fact, it's an antibody that just happens to recognise the receptor.

06:10 So we're going to get massive activation of the thyroid.

06:14 This is Grave's disease, a thyrotoxicosis related to too much stimulation driven by the antibody.

06:21 There's no damage here.

06:22 There's no complement activation.

06:24 The antibody type is such that we're not getting any phagocytosis, we're not getting opsonization, we're not getting complement activation.

06:33 Another example, is on the right hand side.

06:37 In this particular case, the patient has developed antibodies to the acetylcholine receptor.

06:41 Acetylcholine receptor, as you'll recall, is what allows the neuromuscular junction to transmit a signal.

06:47 Nerve signal comes along from the nerve.

06:50 You then get to the terminus, you release acetylcholine into the synapse between the nerve and muscle, you get muscle contraction via the interaction of acetylcholine with its receptor.

07:02 If you make an antibody that blocks that receptor, the neurons firing all at once and the muscles not responding because it can't.

07:09 The antibody has blocked the ability of the acetylcholine to get to its receptor.

07:16 There's no damage here.

07:17 The isotype again is not going to activate much compliment.

07:21 It's not going to recruit Fc receptor bearing cells but it's going to block the movement.

07:27 This disease is Myasthenia gravis.