Immuno 17: Transplant Immunology

Question 1

What is an alloantigen?

Answer 1

antigen which varies between members of the same species

Question 2

What are alloreactions?

Answer 2

immune responses directed against alloantigens

Question 3

What are immunogenetics?

Answer 3

a subfield of immunology devoted to the genetics of alloantigens

Question 4

What is an autograft?

Answer 4

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

Question 5

What is a syngeneic graft or isograft?

Answer 5

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

Question 6

What is an 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

Describe transplant rejection.

Answer 7

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

Question 8

What is a graft vs. host (GVH) reaction?

Answer 8

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

Question 9

In the process of transplantation, how is it possible for the recipient to tolerate an allogeneic graft?

Answer 9

systemic suppression of immune response must be elicited

Question 10

What is the basis for immune responses mounted by a recipient that are directed at transplanted tissues?

Answer 10

genetic differences between the donor and recipient, including polymorphic gene expression, for example, of MHC molecules–most important being MHC Class I

Question 11

Is a blood transfusion a type of tissue transplantation?

Answer 11

Yes - it’s the easiest and most commonly used tissue transplantation procedure

Question 12

How long are transfused blood components needed by the recipient?

Answer 12

a short time until the donor’s bone marrow can replenish the blood lost during surgery or trauma

Question 13

Why are the alloantigens that normally cause most rejections not a problem in blood transfusions?

Answer 13

RBCs don’t express mHC class I or class II molecules, therefore there are no alloantigens to cause a problem

Question 14

What is the basis of life-threatening reactions that can result from blood transfusions?

Answer 14

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

Question 15

Why do many people produce antibodies to the blood group antigens that are different from their own?

Answer 15

Because blood group antigens are similar to surface carbs found on many bacteria that most people have been infected with at one point

Question 16

Why should a person with type O blood not receive Type A or B blood?

Answer 16

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

Question 17

What does the commonly used term “Rh factor” really refer to?

Answer 17

the RhD factor, antigen present on the surface of RBCs; this factor is very important with respect to blood transfusions

Question 18

True or False: A person with RhD- blood can receive RhD+ blood, but a person with RhD+ blood cannot receive RhD- blood.

Answer 18

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.

Question 19

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?

Answer 19

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.

Question 20

What is hyperacute transplant rejection?

Answer 20

very rapid graft rejection (12-48hrs)

Question 21

In addition to the surface of RBCs, A/B/O antigens are expressed where? (which is important to consider in transplanting organs)

Answer 21

vascular endothelium; because vessels run through organs

Question 22

What is a panel-reactive antibody, or PRA?

Answer 22

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

Question 23

Preformed antibodies specific for allogeneic HLA antigens can also mediate ____ ____ ____.

Answer 23

hyperacute graft rejection

Question 24

What mediates acute graft rejection, and what is the time frame?

Answer 24

effector T cells; 11-15 days

Question 25

What is a major difference between the hyperacute graft rejection and the acute graft rejection in terms of immune response?

Answer 25

hyperacute is mediated by preformed antibodies, whereas acute is mediated by effector T cells that must be initiated

Question 26

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

Answer 26

1. direct pathway | 2. indirect pathway

Question 27

Describe the direct pathway by which HLA molecules can stimulate acquired immune responses.

Answer 27

naive T cells of the recipient recognize donor-self-peptides loaded onto donor HLA molecules on donor APCs

Question 28

Describe the indirect pathway by which HLA molecules can stimulate acquired immune responses.

Answer 28

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

Question 29

What type of T cells are activated by the indirect pathway?

Answer 29

CD4+ T cells; they participate in the acute rejection and also go on to mediate the chronic rejection response

Question 30

The ____-specific antibody response mediates chronic transplant rejection.

Answer 30

alloantigen

Question 31

In what time frame does chronic rejection occur?

Answer 31

months or years after transplantatoin

Question 32

What blood vessel changes characterize chronic rejection?

Answer 32

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

Question 33

Antibodies to which MHC class molecules seem to be most responsible for mediating chronic rejection?

Answer 33

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

Question 34

To improve transplantation outcomes, what 2 things can be done?

Answer 34

1. HLA matching | 2. immune suppression

Question 35

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.

Answer 35

True :(

Question 36

What two types of immunosuppressive drugs are useful for reducing the recipient's immune reactivity to allogeneic tissue grafts?

Answer 36

corticosteroids and cytotoxic drugs

Question 37

In what two tissues is HLA matching not necessary?

Answer 37

- cornea - because it's avascular and unavailable to immune effectors - liver - hepatocytes don't really produce HLA class I or II

Question 38

Unlike solid organ transplants, where alloreactions are limited to _________, alloreactions following bone marrow transplantation are ____.

Answer 38

the transplanted organ; systemic

Question 39

What are the primary targets for graft vs. host disease?

Answer 39

skin, intestines, liver

Question 40

GVHD is mediated by what?

Answer 40

mature T cells in the donor tissue that reacts to antigens of the recipient’s tissues

Question 41

How can GVH disease be prevented?

Answer 41

by depleting mature T cells from the bone marrow prior to grafting; drug treatment can also help to control the incidence and severity