What is up with this?

[Guest]

One of my buddies in FL is taking an immunology class and recently had this bit of discussion online with the professor....

My buddy's post:
In the book [Basic Immunology: Functions and Disorders of the Immune System], on page 190, it says that allogenic and xenogenic grafts are always rejected. "Allogeneic and xenogeneic grafts, also called allografts and xenografts, are always rejected." That can't be correct, can it? If so, that leaves no basis for organ donation. And I know that pig's cardio-pulmonary parts have seen some time in people. A friend of mine actually has a pig's valves in his heart. Been about 8 months now, and no rejection... And also, like 2 lines down, the book says "In the clinical situation, transplants are usually exchanged among allogenic individuals, who are members of an outbred species who
differ drom one another (except, of course, for identical twins)." What is going on there?

His professor's response:
The allogeneic grafts [implants from the same species...i.e. human to human] are always rejected unless they are matched and/or medication to stop the immune reaction is given. Prior to matching and immunosupressive therapy, grafts were not successful. Xenogeneic grafts [implants from different species...i.e. pig to human] will survive for short periods of time
if sufficient immunosupression is provided. The more important problem with xenogeneic transplants is hyperacte rejection caused by exisiting antibodies in the recipient against the membranes to the foreign cells resulting in complement activation and cell lysis. Research to develop transgenic pig grafts that have
similar cell membrane properties along with inibiting the complement system activation is being done.

My reponse:
As far as I know, I have a pig's valve in me...LOL...but, the book and the professor seem to be saying that that isn't possible...that xenogenic grafts (i.e. implants from another species) are always rejected. AFAIK, I have not had any problems with rejection with any of the pig valves I've had in me....and, as far as I know, I'm not on any immunosupressive drugs.....

Need your expertise/knowledge:
So, how do I/we respond to this? I'm giving my buddy the link to this thread so he can keep track of it and report back to his professor....

I just hope it don't turn out that I'm completely nuts . ROFLOL!

Peace...always,
Cort S, pig's valve & pacemaker-enhanced 29/swm
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[ShadowLvr400]

I'm the friend in the class. Figured I could help define some of the language used, and also update on the professor's response when I get one.

Hyperaccute reaction: An antibody reaction, powered by antibodies and the complement system. Basically, chemicals floating in the blood that can instantly react to foreign particles. This reaction is very fast, and very obvious, with inflammation, and rapid damage to the foreign particles. Would be noticed within minutes. An allergic reaction would be a good example.

Some immunosuppressive drugs:

Cyclosporine-blocks the cytokine production (chemical directions/orders) of T-cells (your commanding officers as it were)

Mycophenolate mofetil-Blocks white blood cell production

Rapamycin-Blocks white blood cell production

Corticosteroids-Reduces inflammation caused by macrophages (Macrophages "eat" foreign chemicals/bacteria etc)

Anti_CD3-monoclonal antibody-Depletes T cells by binding to CD3 (one of the initial attacking chemicals) and promoting phagocytosis (eating) or complement-mediated lysis (the chemical attack)

Anti_IL2-receptor antibody-Inhibits T Cell production

CTLA4_Ig-inhibits T cell activation

Anti_CD40 ligand-Inhibits macrophage and endothelial (thin layer of flat epithelial cells that lines serous cavities, lymph vessels, and blood vessels) activation

So if anyone's on any of the above drugs, you are indeed on a form of immunosuppressive therapy. (lowers your resistance to sickness)

 

[Ross]

I know of no one taking any type of anti rejection drugs for Porcine or Bovine valves or Homograft for that matter. This should be an interesting thread.

Here is a partial answer:

Tissue Valves
A tissue valve, also known as a xenograft, is a natural tissue or biological valve that has been taken from an animal heart. After the valve is removed, it is treated to make the tissue stronger and prevent the recipient from rejecting the tissue.

 

[Nancy]

Maybe in the past it was a problem

Maybe in the past it was a problem

I believe that's why these valve materials are now treated to eliminate the possibility of rejection.

Having said that, Joe had his first aortic valve replacement in 1977. He was due to get a porcine valve, but testing was done on him and it was found that this valve tissue could not be used because there was some kind of reaction when they did testing. What testing that might be, I have know idea. It was a long time ago. Sounds like it might have been a rejection type of thing???

His surgeon then, told him it would have to be a mechanical valve, and apologized to him, because there wasn't much data on the longevity of that particular mechanical or any others for that matter. Joe lucked out though, that old mechanical is still in there and working along.

So it's quite possible in the past there were rejection problems. I guess there could be with any foreign object. Not sure, not my field.

I hope the textbooks are up to date

 

[Yokena]

Valve Rejection

Valve Rejection

I think the textbook is talking about transplants of living tissue, such as organs. What we have is not living (so it does not need to "survive"). In addition, as someone pointed out, the porcine and bovine valves are both treated and coated before they go in. They have a mesh of some kind of material on them to increase their durability.

We could check out the web pages for the makers of the valve, too, and see what they have to say about this.

Interesting topic!

Joyce

 

[bvdr]

I do think if I had a pork allergy I would think twice about a porcine but I bet the issue of rejection has pretty much been dealt with because as already stated it is not living tissue.

Betty (bvdr)

 

[ShadowLvr400]

It's non-living tissue? Hmm wasn't aware of that. Though to the immune system, that doesn't change anything. Foreign cells, whether dead or alive, are still foreign to the immune system. The body would still destroy and dispose of the cells. As for mechanical valves, the body isn't very good at removing metals.

Basically there are two main sets of immune system. 1 is the cell mediated response, this is the attacker cells. It's slower, but it learns. It can only see protein fragments. All organic cells are based on this. And these fragments must be "displayed" in a certain fashion. MHC 1 and MHC 2 are the displayers. All cells with a nucleus have MHC 1. This is why blood transfusions aren't often rejected. No display MHCs. MHC 2 are on "professional" display cells. These take the intruder and hands it to the T-cells to be taken care of.
The other secton of the immune system (humoral) is more general. It's mostly anitbodies and chemicals that float in the plasma. These respond to lipids (fats), proteins, acids, sugars, shapes, just about everything. This part of the immune system is less specific. Analogy would be the cell mediated has the key to open 1 specific tpye of car, like Ford Taurus's. The humoral can open all Fords. But to get better, parts of the humoral must be "taught" by the cell mediated.

However most metals can't be recognized by either section. Tis why metal poisons like mercury are so deadly. But back to the point I might have had somewhere... Even dead tissue implanted would still trigger an immune response. The basis of many vaccines, is injecting a dead or weakened bacteria or virus to stimulate the cell mediated immune response. (the smart one)

The best overall analogy I've come up with, is the humoral immune system is a basic soldier. He sees a certain thing, he shoots it, no questions. But anything that requires any sort of planning or thought, the commander is the cell mediated response. Hehehe going over all of this will help me on my test this week too.

 

[Nancy]

I did a search on Google with the phrase:

"heart valves" rejection

and the phrase:

"heart valves" immune

Lots of hits.

Here are some that might be interesting: There are lots more

http://www.rds-online.org.uk/pages/page.asp?i_ToolbarID=3&i_PageID=125

http://www.me.utexas.edu/~uer/heartvalves/mechanics.html

http://www.mse.cornell.edu/courses/mse265/html/heart valves.html

http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=12324726&dopt=Abstract

http://www.hc-sc.gc.ca/hpfb-dgpsa/bgtd-dpbtg/xeno_fact_e.html

http://strategis.ic.gc.ca/epic/internet/inbac-bec.nsf/vwGeneratedInterE/h_bk00291e.html

 

[Nancy]

Here are a couple more that I found after doing a search using the word synergraft


http://www.thieme.de/thoracic/abstracts2003/daten/v203.html

http://www.islet.org/forum014/messages/10276.htm


You might want to read many of the Google hits on Synergraft. The concept is interesting and we do have a few members who have had synergraft implantations. I'll let them post about it, if they see this. You could search this site using synergraft also.

Synergraft (Cryolife) ran into some difficulties with the preservation process they use on some of their prosthetic items. I'm not sure the heart valves were included, can't remember, but you might want to search on that issue as well.

Do we have a budding biomedical engineer here?

 

[ShadowLvr400]

Posted by KATHY BLANEY (pcb3233) on Sunday, July 20, 2003 9:33pm
A discription of the valve you may be referring to can
be found on the internet. For a porcine heart valve to
not be rejected it is "depopulated of the antigenic
cells", much like bone and certain tissues that can be
"freeze-dried". The graft forms a basis of support for
the repopulation of the recipient's cells. Since the
graft is free of foreign antigen, it is not normally
rejected. The web site is WWW.cryolife.com






(Back to me now) So the fact that it is dead cells is a part of the aiding issue here. Basically, the porcine valves are stripped of their identifying flags so the immune system doesn't see them. And on a time crunch right now, so off to school.
Side note, not planning on biomedical engineering, it's a bit too research based for me. Planning on being a pain management specialist, but I like to know at least a bit about everything. But now I'm running late. *poof*

 

[bvdr]

Thanks Nancy. I see that on the Canandian sites the terms
"functional, living tissue" are used. They say that the valves are not considered "functional, living tissue" after their pre-treatment.

Maybe that is the bridge phrase here.
Thanks Shadow for the food for thought.

Betty(bvdr)