Tissue Reaction to Foreign Bodies

00:01 Let's talk here and turn our attention to how we respond to so called inert foreign body.

00:06 So as we get clever and clever about putting in various devices, we are also learning that the body doesn't necessarily leave Teflon alone that in fact, there is a response to so called inert foreign bodies.

00:22 So how is this happening? Because they don't express antigens in the way that we normally would think about.

00:27 So first off, there's surgical trauma.

00:29 If we implant something and this is, the slide is showing here, a suture a non resolvable suture that is in the tissue.

00:37 So there's trauma the surgeon is magical. Yes, they are.

00:40 They have great hands, but they are not godlike.

00:42 They cannot just insert things without having an incision.

00:45 That incision causes local trauma, local injury and cell death that will elicit as part of the normal healing process acute and then chronic inflammation.

00:56 We will also have thrombosis, haemorrhage and thrombosis related to the fact that vessels are being cut.

01:02 And the components of the thrombotic pathway will also elicit an inflammatory response.

01:10 So we are calling the in the cells as part of the normal healing process due to the surgical incision and the haemorrhage and thrombosis.

01:19 And we're going to activate these cells in that location, they're going to be doing their job.

01:26 There will be on the surface of whatever we insert, denature proteins, so denature proteins from a thrombus, denature proteins from the tissue that's been damaged, and just proteins that absorb and then unfold and are present there.

01:42 And between the fibrinogen, for example, coming from the circulation or denatured extracellular matrix proteins, that's what ECM is, we will get activation of the innate immune system.

01:55 Again potentially seen newly exposed peptide motifs, different parts of the protein that would normally be folded within the inside.

02:05 And we're getting a secondary now immunoresponse.

02:08 As though cells have denature proteins or has those tissues have denature proteins and the thrombotic pathway gets activated, we will also have complement components that get activated again, now, bringing in through complement receptors.

02:28 The other inflammatory cells.

02:31 They come in they attempt to remove the foreign body, whether it's suture, whether it's a breast implant or at brand new hip, and there is frustrated phagocytosis we've talked about that.

02:44 So the macrophages not specifically my name, for example, to a piece of suture can't get their pseudopod around it, they nevertheless still fuse their lysosomes with that surface, and will dump their contents containing proteases and reactive oxygen species (ROS) into that location.

03:03 There will also be as we have local tissue injury and destruction, growth factor release that's already in the extracellular matrix that will drive the proliferation and activation of fibroblasts.

03:15 And the inflammatory cells, it's not just the T cells that can make cytokines, macrophages and neutrophils and even the tissues cells within the tissue can make cytokines.

03:26 So all this is happening just as a response to in so called inert material.

03:33 A combination of the ongoing damage from the release of the proteases in reactive oxygen species.

03:39 Growth factor release, cytokine elaboration, all of that will lead to fibroblasts proliferation, and deposition extracellular matrix and will form a scar around it.

03:52 And then we can under the appropriate circumstances.

03:56 So with denatured proteins, we may be exposing cryptic motifs that weren't there previously or weren't accessible previously.

04:05 And so we can potentially in some cases, even when it's an inert foreign body, elicit an adaptive response to denatured or otherwise modified self antigens.

04:18 And so you can have them the adaptive immune response, T cells and B cells get involved.

04:23 So what's being shown here is a suture granuloma, the kind of refractometer in the middle is a suture around the outsider, a big zone of activated macrophages elaborating cytokines and causing all the things that we talked about including local scarring.

04:38 So in inert foreign body is not inert.

04:42 For all the reasons that we've just discussed.

04:44 The immune system gets involved.