Fetal/Transplant Immunology Flashcards
What is the major barrier to transplantation?
MHC
Why are allogenic tissues antigenic?
Accidental resemblance causes massive T-cell response
The allo-MHC + self-peptide is recognized by a T-cell that normally recognizes self-MHC:antigen.
What is the “direct” mechanism of rejection?
Activation of the immune system by the foreign MHC marker itself without any form of MHC processing or presentation (Allo-MHC presentation of self-peptide)
- Direct method is known as “heresy” as it doesn’t follow the MHC restriction concept of Ag presentation in the context of one’s own MHC but the phenomenon has ben reatedly observed experimentally
What is the “indirect” mechanism of rejection?
Standard recognition- alloantigens are phagocytized, processed and represented in context of class II MHC antigens by APCs to CD4 T cells
What are two things to test for when determining donor/recipient compatibility?
1) Use ELISA/flow to look for recipient antibodies that might cause rejection of a transplanted organ
2) Use DNA sequencing to determine if MHC loci match
Which is the most important loci for MHC matching?
MCH Class 2 (DR) matches are more strongly predictive of graft survival
Hyperacute rejections of a transplant are generally mediated by what immune effector?
Antibodies.
Hyperacute rejection is defined as accelerated rejection, usually within the first 48 hours after transplantation. This type of rejection is mediated by recipient alloantibody directed against donor antigens that were present prior to transplantation
Define an acute rejection.
Acute rejection is defined by the sudden appearance of anti-donor organ immune effector cells in the first 10-90 days after grafting. The rejection sequence is initiated when host recipient CD4 T-cells react with alloantigens, either directly or indirectly, and mediate an TMMI-type response
What is chronic rejection?
Chronic rejection is a slow process of graft attrition caused by immunologic mechanisms that are probably distinct from those of acute rejection. The hallmark of chronic rejection is diffuse, widespread arteriolar narrowing caused by intimal thickening of the vessel.
Chronic rejection is the leading cause of re-transplantation of hearts and gradually loss of transplanted lung and kidney function
What is graft vs host disease?
Inadvertent transfusion of immunocompetent cells into an immunodeficient host.
This is unique to bone marrow transplanation
How do we treat GVHD?
GVHD is untreatable
What are two methods of achieving immunological tolerance to a transplanted organ?
1) Provide inhibitory second signals (CTLA-4 or IL-10/TGFbeta) to override Th1 and CD8 responses
2) Induce specific tolerance to the organ through induction of Tregs
How does the fetal immune system respond in the opposite manner to the adult immune system?
They acquire tolerance against incoming antigens instead of immunity
This causes rapid growth of infecting agents
Describe the local maternal/fetal strategies for the prevention of rejection.
Trophoblastic tissue does NOT display the “classic” HLA-A, HLA-B, HLA-C fetal molecules because the MHC at the maternal/fetal interface is down-regulated.
Instead, trophoblastic tissue displays only a “non-classical” HLA system, HLA-G that has an inhibitory motif for maternal NK cells
Where are HLA-G molecules displayed?
Wherever trophoblastic tissues invade the uterine wall to establish and maintain pregnancy
