Question 1

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I)that best matches it.
-Can induce anergy in T cells through inhibition of costimulatory signaling

Accepted Answer

CTLA4-Ig is a fusion protein that binds to B7-1 and B7-2 and therefore blocks B7 binding to CD28.This is a method of blocking costimulation.If,at the time of transplantation,alloantigens provide signal 1 to alloreactive T cells,while signal 2 is blocked by CTLA4-Ig,the alloreactive T cells may become anergic.

Question 2

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I)that best matches it.
-Blocks calcineurin-dependent activation of NFAT

Accepted Answer

Cyclosporine is a cyclic fungal peptide that inhibits calcium-dependent calcineurin and thus prevents the dephosphorylation of NFAT.NFAT is an essential transcription factor for numerous T cell cytokine genes,including interleukin-2.

Question 3

For each of the descriptions in questions ,choose the blood group antigen (A-E)that best matches it.
-Nonglycosylated red cell membrane protein missing or mutated in 15% of humans

Accepted Answer

About 15% of individuals do not express the RhD protein,and therefore mount immune responses to RhD+ cells introduced by transfusion or during pregnancy.RhD is the major antigen associated with hemolytic disease of the newborn.

Question 4

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I)that best matches it.
-Inhibits a lymphocyte-specific isoform of inosine monophosphate dehydrogenase,an enzyme that is required for the synthesis of guanine nucleotides

Accepted Answer

Mycophenolate mofetil (MMF),like azathioprine,inhibits the maturation and proliferation of T cells.MMF is metabolized to mycophenolic acid,which blocks a lymphocyte-specific form of an enzyme required for the de novo synthesis of guanine nucleotides.

Question 5

For each of the descriptions in questions ,choose the blood group antigen (A-E)that best matches it.
-Blood group of a person whose red blood cells can only transfused to a person with the same blood group

Accepted Answer

AB blood can only be transfused into people with no anti-A or anti-B antibodies,which are only type AB people.

Question 6

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I)that best matches it.
-Inhibits mTOR,and thereby inhibits IL-2 driven cell cycle progression in T cells

Accepted Answer

Rapamycin is an antibiotic that binds to FK506 binding protein (FKBP)and inhibits T cell proliferation.The rapamycin-FKBP complex does this by binding another cellular protein,the mammalian target of rapamycin (MTOR),which has been observed to regulate cell cycle progression by modulating the expression of certain cyclins.Note that FK506,another immunosuppressive drug,also binds FKBP,and the complex binds and inhibits calcineurin,as does cyclosporine.

Question 7

Which type of molecules are the most frequent target of allogeneic immune responses against transplanted organs and why?

Accepted Answer

The genes encoding HLA molecules,which include class I and class II major histocompatibility complex (MHC)proteins are the most polymorphic genes in the genome,with thousands of different alleles.Therefore,allogeneic responses against HLA proteins are more likely to occur than any against other type of molecules,including endothelial adhesion molecules or cytosolic proteins.Since HLA molecules are present on graft endothelial cell membranes,they are also easily seen by recipient antibodies and T cells.Differences in blood group antigens between donor and recipient are screened for and transplantation between blood group incompatible individuals is rarely performed.

Question 8

Allogeneic immune responses lead to graft rejection.Which of the following best defines an allogeneic immune response in human-to-human transplantation?

Accepted Answer

Allogeneic immune responses are against molecules that are different between graft donor and graft recipient.Within species,molecular differences are largely due to genetic differences,i.e.polymorphisms of genes encoding the same molecules.Other than identical twins,all humans,including other family members,have many different versions,i.e.alleles,of genes encoding the same proteins.These differences are detected by the adaptive immune system in graft recipients,and stimulate allogeneic immune responses.The innate immune system does not recognize allogeneic differences.

Question 9

For each of the descriptions in questions ,choose the blood group antigen (A-E)that best matches it.
-Antibodies specific for this blood group found in a person with type A blood.

Accepted Answer

People make natural antibodies to blood groups they do not express.Type A people make anti-B,type B people make anti-A,type O people make both anti-A and anti-B,type AB people do not make either anti-A or anti-B.

Question 10

For each of the descriptions in questions ,choose the blood group antigen (A-E)that best matches it.
-The blood group of a red blood cell blood donor than can be transfused to any recipient.

Accepted Answer

Group O donors have neither A or B antigen on their red blood cells,and therefore,preformed anti-A or anti-B antibodies in any recipient will not bind to and cause lysis of the donor cells.

Question 11

Which of the following is a correct description of direct T cell recognition of allogeneic MHC molecules by graft recipients?

Accepted Answer

Many T cells in any individual can recognize and be activated by intact allogeneic MHC molecules,whether or not the peptides bound to the allogeneic MHC are polymorphic and different from self-peptides.This can be considered a cross-reaction of T cells that normally would recognize microbial peptides bound to self-MHC.The high frequency of T cell that can directly recognize allogeneic MHC is one reason why allogeneic T cell responses are so frequent and strong in graft recipients.Indirect allogeneic MHC recognition,described in choice B,also occurs in graft recipients.
Matching

Question 12

A kidney is transplanted into a patient with renal failure to diabetes,and within 15 minutes after the recipient blood supply to the graft is established,the graft becomes pale,and stops functioning.Microscopic analysis of the failed graft shows death of cells due to lack of blood flow ("ischemic necrosis").What is the most likely cause of this graft failure?

Accepted Answer

The rapid development of ischemic necrosis in the graft is diagnostic of hyperacute rejection,which is always caused by antibodies against graft endothelial antigens already circulating in the recipient before the transplantation.The preexisting antibodies may be natural anti-blood group antigens,if the donor and recipient are of incompatible blood types,or anti-HLA antibodies if the recipient has had previous pregnancies or received transfusions transplants in the past.Acute rejection requires the recipient T and B cells to be activated,over the course of several days.Chronic rejection takes months to develop.Damage to kidneys due to diabetes takes years to develop.

Question 13

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I)that best matches it.
-Inhibits macrophage cytokine secretion

Accepted Answer

Corticosteroids are potent anti-inflammatory agents that are thought to block the synthesis and secretion of cytokines,primarily tumor necrosis factor and interleukin-1,by macrophages.Inhibition of these cytokines results in reduced graft endothelial cell activation and inflammatory cell recruitment.Corticosteroids are also thought to block other effector functions of macrophages,such as the production of reactive oxygen intermediates and nitric oxide.

Quiz 19: Transplantation

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I) that best matches it. -Can induce anergy in T cells through inhibition of costimulatory signaling

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I) that best matches it. -Blocks calcineurin-dependent activation of NFAT

For each of the descriptions in questions ,choose the blood group antigen (A-E) that best matches it. -Nonglycosylated red cell membrane protein missing or mutated in 15% of humans

For each of the descriptions in questions ,choose the blood group antigen (A-E) that best matches it. -Blood group of a person whose red blood cells can only transfused to a person with the same blood group

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I) that best matches it. -Inhibits mTOR,and thereby inhibits IL-2 driven cell cycle progression in T cells

Which type of molecules are the most frequent target of allogeneic immune responses against transplanted organs and why?

Allogeneic immune responses lead to graft rejection.Which of the following best defines an allogeneic immune response in human-to-human transplantation?

For each of the descriptions in questions ,choose the blood group antigen (A-E) that best matches it. -Antibodies specific for this blood group found in a person with type A blood.

For each of the descriptions in questions ,choose the blood group antigen (A-E) that best matches it. -The blood group of a red blood cell blood donor than can be transfused to any recipient.

Which of the following is a correct description of direct T cell recognition of allogeneic MHC molecules by graft recipients?

For each of the descriptions in questions ,choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I) that best matches it. -Inhibits macrophage cytokine secretion