Transplant Rejection Flashcards
Hyperacute Rejection
Mediated by: pre-formed antibodies that are specific for alloantigens that are expressed on the grafted tissue.
Most common cause: transplantation of tissue from a donor whose blood type is not compatible from recipient’s blood type.
Effector molecules: complement and phagocytes
Time: 48 hours
Process: vascular endothelium expresses the same antigens that are present on RBCs. A donor’s tissue will therefore come with the same antigens the patient’s blood had. If blood types are not compatible, then the recipient’s antibodies will bind to the antigens expressed on the vascular endothelium of the donated tissue, initiating complement cascade and phagocyte influx into the donated tissue. The phagocytes produce inflammatory mediators, causing platelets to bind as well to the activated endothelium. Occlusion of vessels results, and the grafted tissue is destroyed/killed within 48 hours of reception.
Acute Transplant Rejection
Mediated by: CTLs that have specificity for alloantigens (usually the highly polymorphic MHC Class I or II molecules) of the grafted tissue.
Time: 11-15 days
Process: The recipient will have no pre-formed immune responses (unlike in hyperacute rejection) to the antigens on the donor tissue; therefore, it will take 11-15 days for the recipient to mount a response against the HLA genes/proteins if no drug treatment is provided.
Notes: Mouse experiments show that rejection time is 11-15 days upon first transplant, but that if another transplant is done between same donor and recipient, rejection time is dramatically reduced to 4-7 days due to the recipient now having a pre-formed immune response.
Two mechanisms for priming acute graft (transplant) rejection
1) Antigen-presenting cells from the DONOR migrate to secondary lymphoid tissues. These APCs will be presenting peptides largely through the MHC Class I pathway to naive T-cells, who will not recognize the peptides as self, but rather, as foreign. They will prime a CTL response to the donated tissue.
2) RECIPIENT antigen-presenting cells can also collect pieces of dead, grafted cells and present them to naive T-cells in secondary lymphoid tissues, again stimulating them to prime a CTL response.
How can you vastly increase the success of a transplant? How do you go about it?
1) Match up the MCH Class I and II haplotypes between donor and recipient (AKA: HLA matching).
2) Perform serological studies and DNA testing to ensure match.
Degree of matching between donor and recipient HLA should be closest at which loci?
HLA-A, HLA-B, and HLA-DR loci
Is it possible for grafted tissue to have identical MHC haplotypes and STILL be rejected? If so, why?
There are these other rather polymorphic dudes called minor histocompatability antigens that are encoded in the MHC locus of genes. The recipient can mount a response against them.
Rejection caused by minor histocompatability antigen: Mediators and time scale?
Mediated by CTLs
Takes 30-60 days without drug treatment
Tell me about liver and corneal transplants. Do they follow the same rules?
1) Liver transplants do not require HLA matching between donor and recipient. BUT you best make sure blood types match.
2) Corneal transplants do not require HLA matching, and no drugs are needed, either. The cornea is not vascularized, so the CTLs couldn’t get there if they wanted to.
Is pregnancy fuckin weird?
Yes.
Pregnancy and immune response
There is not one. Possible reasons include: 1) the placenta is fetal tissue and lacks MHC Class I and II molecules; 2) The placenta and uterine epithelium produce TH2 cytokines that down-regulate cell-mediated immune response.
What are Rh antigens?
Why are they important for tissue transplantations?
They are a set of antigens that can be expressed on red blood cells.
They affect donor/recipient match-ups when it comes to blood transfusions. For example, A Rh+ can only donate to A Rh+ and AB Rh+, whereas A RH- can donate to A and AB Rh+ and -.
RhD is most important because 15% of people do not express and are therefore not tolerant to it. RhD(-) recipients of blood or tissue can develop immune responses against donor tissue if it has RhD.
Are Rh antigens important to address with pregnant women?
If they are, what do we do about them?
Yes. If an RhD(-) woman is carrying an RhD (+) child, but they both have the same blood type, this could be problematic for her next pregnancy:
1) During childbirth, fetal RBCs get into the mother’s circulation, and the mother primes a B-cell immune response to their RhD+ factor. If her next kid happens to be RhD+, then the IgGs she created in response to the first kid will cross the placenta and attack the RBCs of the baby, causing erythroblastosis fetalis. (The same pattern of events could occur if the mother is injured prior to childbirth and fetal RBCs enter her circulation.)
2) Give her RhoGAM! It’ll bind to the RhD+ RBCs that enter her bloodstream and kill them before the mum’s immune system can respond.
Erythroblastosis fetalis
Caused when an RhD- mother is carrying her second RhD+ child and not receiving RhoGAM.
Anemia, immune complex deposition (all of the released antigens from the destroyed RBCs), enlargement of spleen and liver, petechial lesions due to low platelet count
Is RhoGAM needed for mums and chillens with different blood types?
No. The mum already has an immune response for blood antigens different from hers, so if a fetal RBC sneaks into her circulation, her pre-existing immune response will take care of it. There will be no new creation of an immune response that can possibly attack a future fetus.
Graft vs. Host Disease (GVHD): What is it, what are the three main problems that arise, and what are the three main symptoms?
1) Cause: Mature T-cells from the donor tissue travel to the secondary lymphoid tissue and start sampling MHC Complexes. They might recognize a peptide that the host doesn’t (as the host has undergone positive and negative selection and gotten rid of many self-reactive T-cells) and mount a response. Unfortunately, this peptide could be expressed all over the body, so the effector T-cells can attack anywhere.
2) The three main problems that arise are inflammation of the skin, bile duct inflammation in the liver, and damage to the intestinal tract
3) The three main symptoms are maculopapular skin rash, high serum levels of bilirubin, and diarrhea.
