transplantation immunology

Question 1

alloantigens-

Answer 1

antigen which varies between members of the same species

Question 2

alloreactions-

Answer 2

immune responses directed against alloantigens

Question 3

immunogenetics-

Answer 3

a subfield of immunology devoted to the genetics of alloantigens

Question 4

autograft:

Answer 4

graft of tissue from one site to another site on the same individual (no rejection results)

Question 5

syngeneic graft or isograft:

Answer 5

graft of tissue from one individual to another individual that is genetically identical (no rejection results)

Question 6

allograft or allogeneic transplant:

Answer 6

graft of tissue from one person to another person that is genetically different (rejection of tissue can result)

Question 7

transplant rejection:

Answer 7

alloreactions developed by a recipient’s immune system that are specific for grafted tissue (tissue is killed)

Question 8

graft vs. host (GVH) reaction:

Answer 8

reaction mounted by mature T cells contained in grafted tissue against tissues of the recipient

Question 9

transplantation of tissues to replace damaged or worn-out organs required solutions to three basic problems:

Answer 9

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)

Question 10

What is the only way to tolerate an allogenic graft?

Answer 10

systemic suppression of immune responses must be elicited for a recipient to tolerate an allogeneic graft

Question 11

What is the main reason of the immune response in transplanted tissues? What is the most important?

Answer 11

genetic differences between the donor and recipient

most important=> differential expression of HLA molecules (MHC class I)

Question 12

What are the barriers to transplanting blood?

Answer 12

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

Question 13

Life threatening alloreactions can result from blood transfusions. What are they based on? What is the primary difference?

Answer 13

structural polymorphisms in the carbohydrates on glycolipids of erythrocyte surface

primary difference=> A, B, O system of blood group antigens

Question 14

What will happen if a person that has type O blood receiving a transfusion of type A or B blood?

Answer 14

anti-A or anti-B Abs will bind to the transfused RBCs

Question 15

anti-A or anti-B Abs will bind to the transfused RBCs. What will be the result?

Answer 15

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)

Question 16

What are the Rh factors? Which is the most important wrt blood transfusions?

Answer 16

50 defined Rh blood group antigens that are polymorphic wrt expression within the population

wrt blood transfusion compatibility is RhD factor

Question 17

What is the a main difference of ABO antigens and RhD? What does this mean?

Answer 17

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

Question 18

What would be the response to an RhD neg person receiving blood from an RhD positive person?

Answer 18

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

Question 19

The fetus is essentially an allograft due to differences in MHC haplotype that can be tolerated. What are the possible mechanisms this can occur?

Answer 19

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

Question 20

when an Rh negative mother carries an RhD+ child, is there a response?

Answer 20

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

Question 21

A RhD- mother is pregnant with her second RhD+ child, what will occur? How?

Answer 21

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

Question 22

How should the problem of an RhD- mother carrying her second RhD+ son be solved?

Answer 22

passive immunization with RhoGam

RhoGam is a preparation of Abs specific for RhD+ RBCs

Question 23

When and to whom should you treat with RhoGam?

Answer 23

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

Question 24

What does Tx with RhoGam prevent?

Answer 24

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

Question 25

Why is Rho Gam occasionally given during a pregnancy? When is it ok for this?

Answer 25

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

Question 26

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?

Answer 26

12-48hrs

hyperacute transplant rejection

Question 27

Other than improper damage to hyperacute transplant rejection, What is another way for hyperacute graft rejection? How?

Answer 27

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

Question 28

How should you find the degree of sensitization of a patient to potential donors?

Answer 28

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

Question 29

What is the mediator of acute graft rejection?

Answer 29

by effector T cells that respond to HLA differences between the donor and the recipient

Question 30

What is the result of acute graft rejection upon first interaction with different MHC? How long does it take?

Answer 30

newly formed acquired immune response that is initiated against alloantigens following the graft procedure

11-15 days

Question 31

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?

Answer 31

acute rejection in 6-8 days due to acquired immune response

Question 32

What are the 2 pathways by which HLA molecules can stimulate acquired immune responses? decribe them

Answer 32

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

Question 33

In the indirect pathway, What is the source of donor HLA molecules?

Answer 33

primarily donor APCs which migrate to 2nd lymphoid tisue of the recipient and undergo apoptoitic death

Question 34

How do the APCs mediate chronic rejection of a tissue?

Answer 34

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

Question 35

What are the primary effectors of the indirect pathway?

Answer 35

CD4 effectors