transplantation immunology Flashcards
alloantigens-
antigen which varies between members of the same species
alloreactions-
immune responses directed against alloantigens
immunogenetics-
a subfield of immunology devoted to the genetics of alloantigens
autograft:
graft of tissue from one site to another site on the same individual (no rejection results)
syngeneic graft or isograft:
graft of tissue from one individual to another individual that is genetically identical (no rejection results)
allograft or allogeneic transplant:
graft of tissue from one person to another person that is genetically different (rejection of tissue can result)
transplant rejection:
alloreactions developed by a recipient’s immune system that are specific for grafted tissue (tissue is killed)
graft vs. host (GVH) reaction:
reaction mounted by mature T cells contained in grafted tissue against tissues of the recipient
transplantation of tissues to replace damaged or worn-out organs required solutions to three basic problems:
1) transplant must be introduced into the recipient in a way that allows it to perform its basic function (relatively routine “plumbing”)
2) health of the donor and recipient must be maintained during the transplant surgery (relatively routine as well)
3) the immune system of the recipient must be prevented from mounting adaptive immune responses that destroy the grafted tissue (may never be considered routine)
What is the only way to tolerate an allogenic graft?
systemic suppression of immune responses must be elicited for a recipient to tolerate an allogeneic graft
What is the main reason of the immune response in transplanted tissues? What is the most important?
genetic differences between the donor and recipient
most important=> differential expression of HLA molecules (MHC class I)
What are the barriers to transplanting blood?
transfused blood components are usually only needed for a short time until the recipient’s bone marrow can resupply the blood components lost during surgery or trauma
since RBCs do not express MHC I or MHC II, alloantigens that cause most transplant rejections are not a problem
Life threatening alloreactions can result from blood transfusions. What are they based on? What is the primary difference?
structural polymorphisms in the carbohydrates on glycolipids of erythrocyte surface
primary difference=> A, B, O system of blood group antigens
What will happen if a person that has type O blood receiving a transfusion of type A or B blood?
anti-A or anti-B Abs will bind to the transfused RBCs
anti-A or anti-B Abs will bind to the transfused RBCs. What will be the result?
complement activation and rapid clearance of the transfused RBCs
(negates the purpose of the transfusion)
results =>
- fever, chills, shock, renal failure, death (symptoms similar to type II hypersensitivity)
What are the Rh factors? Which is the most important wrt blood transfusions?
50 defined Rh blood group antigens that are polymorphic wrt expression within the population
wrt blood transfusion compatibility is RhD factor
What is the a main difference of ABO antigens and RhD? What does this mean?
no structures on normal flora bacteria that are similar to RhD antigen
people that do not express RhD will not have Abs specific for RhD in their circulation
What would be the response to an RhD neg person receiving blood from an RhD positive person?
they will produce an RhD specific Ab response
any subsequent transfusion with RhD positive blood will cause an experience to be life threatening blood reaction
The fetus is essentially an allograft due to differences in MHC haplotype that can be tolerated. What are the possible mechanisms this can occur?
placenta may serve as a partial barrier to the mother’s T cells; the placenta is fetal tissue and lacks expression of MHC I
array of cytokines that are expressed by the trophoblast (placenta) and the uterine epithelium;
^ produces Th2 type cytokines that tend to promote Ab responses while supressing T cell mediated responsiveness
when an Rh negative mother carries an RhD+ child, is there a response?
NO immune response directed agaisnt the fetus
during birth, mother is exposed to a relatively large quantity of fetal blood so there will be an RhD+ immune response
A RhD- mother is pregnant with her second RhD+ child, what will occur? How?
the preformed RhD- specific immune response (RhD-specific IgG producing B cells) produced by the mother (after exposure in 1st pregnancy) will attack the new fetus
IgG can cross the placental barrier
How should the problem of an RhD- mother carrying her second RhD+ son be solved?
passive immunization with RhoGam
RhoGam is a preparation of Abs specific for RhD+ RBCs
When and to whom should you treat with RhoGam?
Treat the mother w/ RhoGam or Rho(D) Ig (IgG specific for RhD) immediately following the 1st birth to destroy all of the fetal RBCs that enter the mothers circulation
What does Tx with RhoGam prevent?
Tx prevents the mother from producing an Rh specific immune resonse by eliminating the antigen before the immune response can be initiated
No problems carrying second Rh+ child
Why is Rho Gam occasionally given during a pregnancy? When is it ok for this?
pregnant mother can have a minor accident that causes fetal blood to enter her circulation
RhoGam can be initiated during the 6th month of pregnancy for most RhD- mothers carrying and RhD+ fetus
What is the time frame of rejection if a person with type O blood receives an organ transplant from donor of type A? What type of rejection is this?
12-48hrs
hyperacute transplant rejection
Other than improper damage to hyperacute transplant rejection, What is another way for hyperacute graft rejection? How?
preformed Abs specific for allogeneic HLA antigens
anti-HLA Abs can be generated in a recipient as a result of immune responses to a previous pregnancy, blood transfusion or previous tissue graft
How should you find the degree of sensitization of a patient to potential donors?
assessed by testing their sera against a panel of individuals from the populations
results expressed as the percentage of positive reactions against the panel => panel-reactive Ab or PRA
What is the mediator of acute graft rejection?
by effector T cells that respond to HLA differences between the donor and the recipient
What is the result of acute graft rejection upon first interaction with different MHC? How long does it take?
newly formed acquired immune response that is initiated against alloantigens following the graft procedure
11-15 days
What is the result if a mouse has already received an allogenic transplant that was rejected, then given a second transplant from the same donor?
acute rejection in 6-8 days due to acquired immune response
What are the 2 pathways by which HLA molecules can stimulate acquired immune responses? decribe them
Direct => naive T cells of recipient recognize self peptides of donor loaded onto donor HLA molecules on donor APCs
Indirect=> peptides derived from donor HLA molecules are processed and presented by recipient APCs to naive T cells of the recipient
In the indirect pathway, What is the source of donor HLA molecules?
primarily donor APCs which migrate to 2nd lymphoid tisue of the recipient and undergo apoptoitic death
How do the APCs mediate chronic rejection of a tissue?
components of dead cells are phagocytosed/endocytosed by resident APCs and antigens are processed primarily via MHC II processing and presentation pathway
CD4 T cell effectors cause an alloantigen-specific Ab response that mediates chronic rejection
What are the primary effectors of the indirect pathway?
CD4 effectors
