Introduction to Type III Hypersensitivity

00:01 That's been a flavour of type two hypersensitivity.

00:06 We're going to now kind of go into type three hypersensitivity which will continue in the next lecture as well.

00:12 So this is immune complex disease related to antigen antibody complex formation.

00:19 I'm showing you an example of administering a particular antigen at a very high level.

00:27 Then this could be in an experimental animal, it could be giving them a foreign albumin.

00:34 In humans, we actually did this back in the day when we were administering horse serum that contained antibodies against the theria.

00:43 And we were trying to cure patients of having diptheria toxin induce cellular death.

00:51 And we would give those antibodies, and that would block the dip there and it worked great.

00:54 It was a neutralizing antibodies.

00:56 But in that horse serum that we were administering to the patients to save their lives from diptheria, there are a lot of other horse proteins in particular horse serum albumin.

01:07 So we would give a large dose to the patients.

01:10 And we would notice it pretty reliably after we did that.

01:14 Usually on the second dose, seven to 10 days later, we got a profound joint inflammatory response, a skin rash, patients could have even had difficulty breathing.

01:26 And it turns out, it's all due to the formation of immune complexes.

01:30 So here at times, here, we've administered a very large dose of a particular antigen, let's say horse serum albumin, and it has a long circulating half life and will eventually be of various mechanisms, including filtration, destruction, and formation of immune complexes go away.

01:49 So at times zero, we administer the antigen.

01:53 Fairly reliably because the immune system is working, we are developing antibodies to that antigen.

01:59 And we will begin formulating immune complexes by about day six to seven.

02:05 The formation of those immune complexes means we have less than less than less of the free antigen circulating and eventually everything goes away at 14 days.

02:12 And obviously, the immune complex is due too.

02:15 Kind of midway at that point as we're forming immune complexes about they can or so.

02:20 If we were measuring it, we would see that the complement level in this patient who received this massive dose of an antigen, the complement level is beginning to diminish.

02:30 That's because it's being consumed due to the formation of immune complexes that are activating the complement cascade.

02:40 At about 14 days, we have lots and lots of free antibody, but there's no more antigen around.

02:47 So that's why we have free antibody and all the antigen has gone away.

02:52 But what was noticed, and what happens pretty reliably is about between a date days, eight and 14 before all the complexes go away, we started getting all these immune manifestations.

03:03 We get a rash, we get joint pain, we have a variety of inflammatory things.

03:09 That's due to immune complex deposition.

03:12 So as we form immune complexes, they're depositing in various vascular beds, activating complement, recruiting FC receptor bearing cells.

03:20 Again, in a predictable way.

03:24 The reason that we're starting to see a lot of disease at this point is because we are in a zone where we have a lot of small immune complexes.

03:34 Those small immune complexes are not very easily cleared, but they will induce complement activation when they deposit.

03:40 They will activate FC receptor bearing cells as they deposit.

03:46 So with that, we've set the stage to talk about immune complex mediated disease, which will be part of the next session.