Transplant Rejection and MHC's

[desiree]

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HI
I have a burning question about Transplant Rejection and it's association with MHC.
According to First Aid it says: "Class II are the main determinants of organ rejection."

But I have come across information in TWO books that seem to contradict this.
According to Hi yield BRS Path: Type IV Cell Mediated Reactions (1. delayed hypersensitivity and 2. T cell mediated cytotoxity)

it says that " T Cell mediated cytotoxity is mediated by CD8 cytotoxic lymphocytes. (we know that CD8 interacts with MHC I )
Clinical Examples: Transplant Rejection

So according to HI yield it says that transplant rejection are associated to MHC I (not MHC II which is stated in FirstAID)

The second source i've found that supports MHC I is from BRS PATH (under HLA SYStems) it says: "Class I antigens are the principal antigens involved in tissue graft rejection"

SO first of all, Is tissue graft rejection the same as organ transplant rejection?
Secondly, is MHC I or II involved in transplant rejection?

The contradicting statements from these 3 sources are wrecking with my brain
Can anyone please shed some light in this matter?
Thanks

 

[mpp]

I would think both MHC Class I and II can be involved. Transplant (or tissue graft) rejection rejection has three phases

Hyperacute, acute, and chronic.

The hyperacute is complement/neutrophil mediated and occurs within 24 hours. This would occure for any antigen encountered by the recipient's humoral immune system and MHC Class I would be the most notable antigen encountered.

The acute phase is mediated both by CD4 and CD8 cells and therefore is involved with both MHC I and II. This can be both cytotoxicic or a delayed hypersensitivity reaction.

Less is known about chronic rejection and I don't think it is important to your question.

 

[desiree]

Thanks for your reply.
So would you say FIRSt AID is wrong in stating that only MHC II is involved in transplant rejection?

 

[1Neuro1]

First Aid is correct but for complex reasons, here is the breakdown:

1. MHC I and II are both important for rejection. They are not as important as ABO blood type however, this applies to organ transplants obviously. ABO mismatch is basically intolerable, modern transplants are allowed to have various degrees of MHC mismatches.

2. The MHC I pathway is indeed the mediator of CD8 cytotoxic rejection, a cell mediated pathway which also involves CD4 helper cells.

3. MHC I mismatches will invoke the CD8/CD4 response and cause rejection.

4. MHCII mismatches will invoke not only the CD8/CD4 pathway, but will also stimulate many more host immune effector cells because foreign MHC II cells will attempt to present foreign Antigens in the context of foreign MHC II to host CD4 cells. This is a "double hit" of foreign Ag which is similar to the lymphocyte proliferation assay. Much more stimulation is provided DIRECTLY to CD4 cells which will further augment the CD 8 pathway. This goes beyond the pure MHC I mismatch pathway and more cytokines are secreted, more lymphs will proliferate. Thus two systems are in place to reject MHC II mismatches: CD8/CD4 as well as the augmented CD4 antigen presentation pathway.

5. To clarify another post, dont automatically assume that any cell mediated immune process is a DTH reaction. Type IV hypersensitivity doesn not always involve granulomas and macrophages!! CD8 cytotoxicity is a Type IV reaction.


I know the above seems very convoluted, to ease your mind, the only immuno I had on Step 1 was much MUCH more basic than this topic. I think I had two questions on very simple immuno in total.

 

[mpp]

I wouldn't say it is wrong since MHC CLass II is probably the main determinant of organ rejection since hyperacute rejection is pretty much a non-issue since donors and recipients would be HLA matched. Therefore, except for chronic rejection of which little is known about mediators, MHC Class II is the main determinant of rejection (i.e., even with matching MHC Class II you can still have organ rejection since other proteins may be antigenic and are presented by allogenic MHC Class II).

 

[desiree]

thanks guys for having taken the time to answer my question.
it was very helpful.