Flashcards in Immuno 17: Transplant Immunology Deck (41):
What is an alloantigen?
antigen which varies between members of the same species
What are alloreactions?
immune responses directed against alloantigens
What are immunogenetics?
a subfield of immunology devoted to the genetics of alloantigens
What is an autograft?
graft of tissue from one site to another site on the same individual (no rejection results)
What is a syngeneic graft or isograft?
graft of tissue from one individual to another individual that is genetically identical (no rejection results)
What is an allograft or allogeneic transplant?
graft of tissue from one person to another person that is genetically different (rejection of tissue can result)
Describe transplant rejection.
alloreaction developed by a recipient’s immune system that are specific for grafted tissue (tissue is killed)
What is a graft vs. host (GVH) reaction?
reaction mounted by mature T cells contained in grafted tissue against tissues of the recipient
In the process of transplantation, how is it possible for the recipient to tolerate an allogeneic graft?
systemic suppression of immune response must be elicited
What is the basis for immune responses mounted by a recipient that are directed at transplanted tissues?
genetic differences between the donor and recipient, including polymorphic gene expression, for example, of MHC molecules--most important being MHC Class I
Is a blood transfusion a type of tissue transplantation?
Yes - it's the easiest and most commonly used tissue transplantation procedure
How long are transfused blood components needed by the recipient?
a short time until the donor's bone marrow can replenish the blood lost during surgery or trauma
Why are the alloantigens that normally cause most rejections not a problem in blood transfusions?
RBCs don't express mHC class I or class II molecules, therefore there are no alloantigens to cause a problem
What is the basis of life-threatening reactions that can result from blood transfusions?
alloreactions based on structural polymorphisms in the carbohydates on glycolipids of the RBC surface; these primary differences are known as A/B/O system of the blood group antigens
Why do many people produce antibodies to the blood group antigens that are different from their own?
Because blood group antigens are similar to surface carbs found on many bacteria that most people have been infected with at one point
Why should a person with type O blood not receive Type A or B blood?
their antibodies will react to the RBCs and clear them, which defeats the purpose of the transfusion; may also elicit symptoms resembling a type II hypersensitivity reaction: fever, chills, shock, renal failure, maybe death
What does the commonly used term "Rh factor" really refer to?
the RhD factor, antigen present on the surface of RBCs; this factor is very important with respect to blood transfusions
True or False: A person with RhD- blood can receive RhD+ blood, but a person with RhD+ blood cannot receive RhD- blood.
False - A person with RhD- blood would recognize RhD+ as foreign and would therefore have antibodies to it. People with RhD+ blood can receive either RhD+ or RhD- blood and be fine.
What about mothers who are RhD- carrying an RhD+ fetus--is there an immune response directed against the fetus? If so, what treatment is available?
It depends - if this is the first RhD+ pregnancy then no there's no antibody response; however during childbirth the mother may be exposed to the enough fetal blood and create an antibody response. Then if she carries another RhD- fetus her immune system will attack the fetus this time. The treatment would be to administer RhoGam immediately after giving birth to prevent an antibody response against the fetal RBCs' RhD+ antigen.
What is hyperacute transplant rejection?
very rapid graft rejection (12-48hrs)
In addition to the surface of RBCs, A/B/O antigens are expressed where? (which is important to consider in transplanting organs)
vascular endothelium; because vessels run through organs
What is a panel-reactive antibody, or PRA?
the degree to which a patient seeking a transplant has been sensitized to potential donors is assessed by testing their
sera against a panel of individuals from the population; the results are expressed as the percentage of positive reactions against the panel: this is the PRA
Preformed antibodies specific for allogeneic HLA antigens can also mediate ____ ____ ____.
hyperacute graft rejection
What mediates acute graft rejection, and what is the time frame?
effector T cells; 11-15 days
What is a major difference between the hyperacute graft rejection and the acute graft rejection in terms of immune response?
hyperacute is mediated by preformed antibodies, whereas acute is mediated by effector T cells that must be initiated
What are the 2 pathways by which HLA molecules can stimulate acquired immune responses?
1. direct pathway
2. indirect pathway
Describe the direct pathway by which HLA molecules can stimulate acquired immune responses.
naive T cells of the recipient recognize donor-self-peptides loaded onto donor HLA molecules on donor APCs
Describe the indirect pathway by which HLA molecules can stimulate acquired immune responses.
naive T cells of the recipient recognize donor-self-peptides loaded onto recipient HLA molecules on recipient APCs; picked up from donor APCs that migrated to recipient lymphoid tissue and apoptosed
What type of T cells are activated by the indirect pathway?
CD4+ T cells; they participate in the acute rejection and also go on to mediate the chronic rejection response
The ____-specific antibody response mediates chronic transplant rejection.
In what time frame does chronic rejection occur?
months or years after transplantatoin
What blood vessel changes characterize chronic rejection?
thickening of the vessel walls and narrowing of the lumina, gradually blood supply is reduced to the point that function of the grafted tissue is lost
Antibodies to which MHC class molecules seem to be most responsible for mediating chronic rejection?
MHC Class I-specific antibodies, that bind to vascular endothelium of grafted tissue and attract Fc receptor bearing cells which cause chronic inflammation and subsequent damage/death of the grafted tissue
To improve transplantation outcomes, what 2 things can be done?
1. HLA matching
2. immune suppression
True or False: suppression of the immune system to allow tolerance to grafted tissue prevents the immune system from reacting normally to pathogens that the host encounters.
What two types of immunosuppressive drugs are useful for reducing the recipient's immune reactivity to allogeneic tissue grafts?
corticosteroids and cytotoxic drugs
In what two tissues is HLA matching not necessary?
- cornea - because it's avascular and unavailable to immune effectors
- liver - hepatocytes don't really produce HLA class I or II
Unlike solid organ transplants, where alloreactions are limited to _________, alloreactions following bone
marrow transplantation are ____.
the transplanted organ; systemic
What are the primary targets for graft vs. host disease?
skin, intestines, liver
GVHD is mediated by what?
mature T cells in the donor tissue that reacts to antigens of the recipient’s tissues