Deck 15: Transplantation of Tissues and Organs

Question 1

_____ describes the process by which transplanted pluripotent stem cells find their way to the bone marrow spaces in the bones of the body and begin to produce new blood cells.

A)Myeloablation
B)Engraftment
C)Relapse
D)Graft-vesus-leukemia
E)Chemotherapy.

Answer 1

B

Question 2

routine blood transfusions,which of the following must be matched correctly? (Select all that apply.)

A)A and B antigens
B)O antigens
C)Rhesus D antigen
D)MHC class I molecules
E)MHC class II molecules.

Answer 2

A,C

Question 3

For the patient's new immune system to function effectively in bone marrow recipients,some HLA allotypes must be shared because _____.(Select all that apply.)

A)professional antigen-presenting cells are host-derived
B)professional antigen-presenting cells are donor-derived
C)otherwise an autoimmune disease would develop
D)newly generated T cells are positively selected on the recipient's thymic epithelium
E)if all HLA molecules were mismatched,acute rejection of the grafted cells would occur.

Answer 3

B,D

Question 4

Which of the following exerts its effect by inhibiting the activation of calcineurin by calcium and thereby interferes with nuclear translocation of NFAT? (Select all that apply.)

A)tacrolimus (FK506)
B)mycophenolic acid
C)cyclophosphamide
D)belatacept
E)cyclosporin A.

Question 5

_____ is a monoclonal antibody administered to transplant patients before and after transplantation in order to induce lymphopenia.

A)Rabbit antithymocyte globulin (rATG)
B)Tacrolimus
C)Alemtuzumab
D)Belatacept
E)Basiliximab.

Question 6

Alloantibodies to blood-vessel endothelium on solid organ grafts _____.

A)are specific for HLA class I and class II antigens
B)cause hyperacute rejection
C)cause acute rejection
D)target endothelium for attack by NK cells
E)are IgA and do not fix complement.

Question 7

In the context of allogeneic transplantation,identify the mismatched pair.

A)inhibition of inflammation: prednisone
B)inhibition of co-stimulation: daclizumab
C)inhibition of cytokine signaling: basiliximab
D)inhibition of calcineurin: tacrolimus (FK506)
E)inhibition of T-cell proliferation: azathioprine.

Question 8

All of the following culminate in complement fixation and removal of T cells by phagocytes except _____ which instead causes the T-cell receptors to be internalized and unavailable for antigen recognition.

A)alemtuzumab
B)OKT3
C)rabbit antithymocyte globulin (rATG).

Question 9

The direct pathway of allorecognition involves interaction of _____,whereas the indirect pathway of alloreaction involves interaction of _____.

A)donor T cells with allogeneic HLA molecule on recipient dendritic cells; recipient T cells with allogeneic HLA molecules on donor dendritic cells
B)recipient T cells with allogeneic HLA molecules on donor dendritic cells; donor T cells with allogeneic HLA molecule on recipient dendritic cells
C)recipient T cells with allogeneic HLA molecules on donor dendritic cells; recipient T cells with peptides of allogeneic HLA molecules on recipient dendritic cells
D)recipient T cells with peptides of allogeneic HLA molecules on recipient dendritic cells; donor T cells with peptides of allogeneic HLA molecules on donor dendritic cells.

Question 10

of the following are commonly used sources of hematopoietic stem cells except ____.

A)skin cells
B)bone marrow
C)umbilical cord blood
D)peripheral blood.

Question 11

_____ results from alloreactions mediated by donor T cells in the graft subsequent to hematopoietic stem-cell transplantation.

A)Acute rejection
B)Chronic rejection
C)Graft-versus-host disease (GVHD)
D)Serum sickness
E)Hyperacute rejection.

Question 12

Which of the following is a permissible match between a blood donor and a recipient (donor: recipient)? (Select all that apply.)

A)O -: AB +
B)O +: AB -
C)AB +: O -
D)A -: A +
E)AB -: O +.

Question 13

The risk of _____ is the primary complication in bone marrow transplants.

A)acute host-versus-graft disease
B)hyperacute rejection
C)chronic rejection
D)acute graft-versus-host disease
E)cancer.

Question 14

_____ is/are a disease or genetic defect that can be treated by bone marrow transplantation.(Select all that apply.)

A)A leukocyte defect
B)Multiple myeloma
C)Hemoglobin defects
D)Celiac disease
E)Acquired immune deficiency syndrome (AIDS).

Question 15

underlying molecular basis for distinguishing blood-group antigens A,B and O is _____ at the erythrocyte surface.

A)the presence or absence of fucose in glycolipids
B)differences in the oligosaccharide attached to the lipid ceramide
C)structural polymorphisms in the Rhesus D antigen
D)the levels of MHC class I and class II molecules.

Question 16

_____ is not a drug that targets replication and proliferation of alloantigen-activated T cells.

A)Rapamycin
B)Methotrexate
C)Mycophenolate mofetil
D)Azathioprine
E)Cyclophosphamide.

Question 17

of the following are characteristics of blood donations and transfusions that enable their extensive use for transplantation purposes except _____.

A)individuals can donate on a regular basis without any deleterious effects
B)erythrocytes do not express MHC class I or class II molecules
C)the blood components only need to function for a few weeks
D)only the ABO antigens need to be compatible between donor and recipient
E)blood transfusion is a straight forward and inexpensive process.

Question 18

What explains the increased incidence of bone marrow graft failure and cancer relapse when mature T cells are depleted from donor bone marrow before engraftment?

Question 19

Blood transfusions mismatched for ABO and/or rhesus antigens are associated with _____.(Select all that apply.)

A)type III hypersensitivity reactions
B)alloreactive immune responses
C)lysis of recipient red blood cells
D)laboratory errors in the cross-matching procedure
E)activation of host complement and destruction of donor cells.

Question 20

Family members who donate their bone marrow to a transplant patient and who share one out of the two HLA haplotypes are providing a(n)_____ transplant.

A)autologous
B)HLA-matched
C)haploidentical
D)chimeric
E)cross-matched.

Question 21

A patient diagnosed with grade IV of graft-versus-host disease would most probably exhibit _____.(Select all that apply.)

A)serum bilirubin levels of 2-3mg/dl
B)jaundice
C)skin blistering and desquamation
D)severe abdominal pain
E)maculopapular rash on less than 25% of body surface.

Question 22

Residual leukemia cells persisting in a patient after they have received chemotherapy,irradiation,and a bone-marrow transplant are sometimes eliminated by a _____ effect which involves the action of _____.(Select all that apply.)

A)graft-versus-leukemia; alloreactive T cells
B)haploidentical; regulatory T cells
C)acute minor histocompatibility; recipient NK cells
D)myeloablation; mature T cells
E)graft-versus-leukemia; alloreactive NK cells.

Question 23

Despite a slower engraftment,cord blood as a source of transplanted hematopoietic stem cells is better than bone marrow or than stem cells derived from peripheral blood in that _____.(Select all that apply.)

A)the recipient does not need to undergo myeloablative therapy
B)there is a higher degree of tolerance for HLA disparity
C)there is a lower incidence of graft-versus-host disease
D)cord blood can be infused directly into the bone marrow of recipients
E)a larger number of stem cells express CD34.

Question 24

_____ from a bone marrow transplant facilitate alloreactive responses,causing the condition defined as acute graft-versus-host disease.

A)Natural killer cells
B)Mature T cells
C)Dendritic cells
D)Thymocytes
E)Mature B cells.

Question 25

Contrast acute rejection and chronic rejection.

Question 26

Males engrafted with HLA-identical bone marrow from their sisters develop graft-versus-host disease because _____.

A)T cells develop in the male thymus that are not tolerant to minor histocompatibility antigens expressed by the sister
B)mature T cells in the graft have specificity for male-specific minor histocompatibility antigens
C)there are differences between the sexes in how self proteins are modified post-translationally
D)NK-cell alloreactions occur
E)residual female hormones in the graft cause upregulation of HLA class I on male dendritic cells presenting minor histocompatibility antigens.

Question 27

George Cunningham was diagnosed with Crohn's disease when 23 years old.He was experiencing acute abdominal pain,diarrhea,rectal bleeding,anemia and weight loss.He did not respond to conventional immunosuppressive therapies and was given a course of infliximab,an anti-TNF-α monoclonal antibody that suppresses inflammation by blocking TNF-α activity.On day 12 after receiving his first infusion,he developed a mild fever,generalized vasculitis,swollen lymph glands,swollen joints and joint pain.Traces of blood and protein were detected in his urine.Which of the following is the most likely cause of these recent symptoms?

A)Type I hypersensitivity involving anaphylaxis.
B)Type II hypersensitivity leading to hemolytic anemia.
C)Type III hypersensitivity caused by immune complex deposition in blood vessels.
D)Type IV hypersensitivity involving CD8 T-cell cytotoxicity.
E)Type II hypersensitivity leading to thrombocytopenia.

Question 28

Explain why an organ transplant made between a donor of blood group AB and a recipient of blood group O will always be rejected,even if it is perfectly HLA-matched and the recipient has been given immunosuppressant drugs.What is this type of rejection called?
B.Give another example of ABO incompatibility between donor and recipient that would lead to this type of rejection.
C.What other antigen incompatibilities,other than those of blood group,are most likely to provoke this type of rejection?
D.Which pre-surgical laboratory test should be performed to prevent this type of rejection?

Question 29

Identify three general classes of drug that are used to suppress acute transplant rejection,and provide examples of each class.
B.What side-effects and toxic effects are associated with each class of drug?

Question 30

The term _____ is used to describe polymorphic antigens that vary between individuals of the same species.

A)xenoantigens
B)immunoantigens
C)alloantigens
D)histoantigens
E)autoantigens.

Question 31

What is the term used to describe the condition of an individual who possesses two sets of hematopoietic cells,one derived from the individual's own bone marrow and one derived from a different source,for example,an organ transplant or blood transfusion that has not been rejected?

A)haploidentical
B)chimeric
C)cross-protected
D)dimorphic
E)mixed lymphocyte reaction.

Question 32

Autologous bone marrow transplantation used to treat cancer patients involves reinfusing a(n)_____-depleted stem-cell population into the patient after their cancer treatment has been completed.

A)mature T cell
B)antibody
C)tumor cell
D)dendritic cell
E)NK cell.

Question 33

Donors treated with _____ can donate bone marrow-derived stem cells from a less invasive peripheral blood draw instead of the more invasive bone marrow aspiration.(Select all that apply.)

A)anti-CD3
B)cyclophosphamide
C)anti-CD34
D)granulocyte colony-stimulating factor (G-CSF)
E)granulocyte-macrophage colony-stimulating factor (GM-CSF).

Question 34

Following a hematopoietic stem cell transplant,T-cell responses will be activated by dendritic cells of _____ origin.

A)donor
B)recipient
C)both donor and recipient.

Question 35

We learned in Chapter 5 that the benefit of having and expressing multiple MHC class I and class II genes is that it increases the number and variety of pathogen-derived peptide antigens that can potentially be presented to T cells.If more is better,then why has natural selection not favored the evolution of more than three genes each for MHC class I and MHC class II?

Question 36

Leukapheresis is used in hematopoietic stem-cell transplantation where stem cells from a suitable donor are fractionated on the basis of their expression of _____.

A)CD3
B)the same major histocompatibility antigens as the recipient
C)the same minor histocompatibility antigens as the recipient
D)the same inhibitory KIR receptors as the recipient
E)CD34.

Question 37

How do the clinical objectives of transplantation differ from those of vaccination?

Question 38

Explain why,in principle,an organ transplanted from any donor other than an identical twin is almost certain to be rejected in the absence of any other treatment.

Question 39

Forty-four-year old Danielle Bouvier is on the waiting list for a kidney transplant and is receiving weekly dialysis.Her HLA type is: HLA-A: 0101/0301; HLA-B: 0702/0801; HLA-DRB1: 0301/0701.Today,Danielle's physician informed her that several potential kidney donors are available.Which of the following would be the most suitable?
a.A: 0301/0201; B: 4402/0801; DRB1: 0301/0403
b.A: 0301/2902; B: 1801/0801; DRB1: 0301/0701
c.A: 2902/0201; B: 0702/0801; DRB1: 0301/13011
d.A: 0101/0101; B: 5701/0801; DRB1: 0701/0701
e.A: 0101/0301; B: 0702/5701; DRBA: 0403/0301.

Question 40

(A)What is a cross-match test? (B)Why is it carried out? (C)How is it carried out?

Question 41

Explain how cyclosporin A acts as an immunosuppressant drug.

Question 42

Richard French,53 years old,was diagnosed with chronic myelogenous leukemia.His elder brother Don is HLA-haploidentical and will donate bone marrow.Richard's oncologist has recommended him to a medical center that favors using bone marrow depleted of mature T cells prior to infusion.The most likely rationale for employing the practice of T-cell depletion is that _____.
a.T-cell depletion will remove alloreactive T cells from the donor and prevent the potential for graft-versus-host disease (GVHD)
b.mature T-cell chimerism is required to establish long-term tolerance
c.because Don is HLA-haploidentical and male,there is no risk of alloreactivity toward major or minor histocompatibility antigens
d.because of Don's age,the expected bone marrow harvest is already marginal for successful engraftment,and depletion measures would compromise the yield of stem cells
e.the benefit of using a cocktail of immunosuppressive drugs outweighs the risk of contaminating the bone marrow during T-cell depletion.

Question 43

In the context of organ transplantation,what is the increased risk associated with an individual's having received previous blood transfusions on multiple occasions?

Question 44

Which of the following are correctly matched? (Select all that apply.)

A)allograft: same person
B)autograft: to treat damage caused by autoimmune processes
C)isograft: syngeneic
D)antithymocyte globulin: xenogeneic
E)same species: allogeneic.

Question 45

What is the name of the clinical test used to determine the compatibility between a donor and recipient requiring a blood transfusion?

A)desensitization
B)cross-match test
C)Arthus reaction
D)HLA typing
E)delayed-type hypersensitivity reaction

Question 46

Graft-versus-host disease (GVHD)is a consequence of _____.

A)mature T lymphocytes from the donor mounting an immune response against tissue of the recipient
B)mature T lymphocytes from the recipient mounting an immune response against tissue of the donor
C)mismatching A,B,and O antigens between donor and recipient
D)mismatching Rhesus antigen between donor and recipient
E)antibodies of the donor stimulating NK cell antibody-dependent cell-mediated cytotoxicity (ADCC)of tissues of the recipient.

Question 47

When an individual receives a kidney transplant,the main concern will be to control the development of _____.

A)graft-versus-host disease
B)transplant rejection
C)xenorecognition
D)allergic reactions
E)lymphoproliferative disorders.

Question 48

Which of the following best explains why a bone marrow donor needs to be HLA-matched to the recipient?

A)The bone marrow transplant contains enough mature T cells to reconstitute the recipient and the recipient provides the antigen-presenting cells.
B)The recipient's MHC molecules mediate positive selection of thymocytes in the thymus that interact with donor-derived MHC molecules in the periphery.
C)Reconstituted T cells are restricted by donor,not recipient,HLA allotypes.
D)Without an HLA match,the donor-derived thymocytes undergo negative selection.
E)If the donor is not HLA matched,the reconstituted T cells will be autoreactive.

Question 49

Alloantibodies specific for HLA class I molecules can mediate hyperacute rejection of kidney transplants.Explain under what conditions an individual would possess preexisting antibodies against HLA class I polymorphisms.

Question 50

Explain why a boy with leukemia who receives a bone marrow transplant from his sister that is perfectly matched for MHC class I and class II is still likely to get graft-versus-host disease.
B.Which effector T cells are usually involved in this reaction,and why?

Question 51

What type of hypersensitivity reaction would result from a mismatched blood transfusion?

A)Type I
B)Type II
C)Type III
D)Type IV

Question 52

Explain how mouse monoclonal antibodies (MoAbs)can be used to suppress acute graft rejection.
B.What feature of these mouse antibodies compromises their effectiveness in vivo and limits their use?

Question 53

From a clinical perspective explain how the logistics of organ transplantation differ from those for a bone marrow transplant.

Question 54

Are the criteria for selecting suitable donors the same for liver and bone marrow transplants?
B.Why or why not?

Question 55

In general the higher the patient's panel reactive antibody (PRA),_____.

A)the higher the number of suitable transplant donors
B)the less likely it is that a hyperacute reaction will occur
C)the higher the risk of developing hemolytic disease of the newborn
D)the more limited the number of suitable transplant donors
E)the higher the risk of developing autoimmunity.

Question 56

Explain why it is necessary to match at least some of the HLA allotypes between donor and recipient in a bone marrow transplant given to remedy SCID.

Question 57

Corticosteroids interfere with chemotaxis of leukocytes by _____.

A)decreasing the production of GM-CSF and IL-1
B)inducing apoptosis
C)inhibiting the expression of adhesion molecules on endothelial vessels
D)suppressing the activity of phospholipase A₂
E)reducing nitrogen oxide synthase (NOS)activity.

Question 58

As time progresses following an organ transplant,the alloreactive T-cell response shifts from a(n)_____ pathway to a(n)_____ pathway of allorecognition.

A)exogenous; endogenous
B)inflammatory; cytotoxic
C)hyperacute; suppressive
D)autologous; heterologous
E)direct; indirect.

Question 59

Which of the following are correctly matched? (Select all that apply.)

A)prednisone: pro-drug
B)rapamycin: calcineurin
C)azathioprine: cytotoxicity
D)methotrexate:
E)cyclophosphamide: microbial products.

Question 60

If _____ occurs in an organ to be transplanted,endothelial activation,leukocyte infiltration,inflammatory cytokine production,and complement activation may occur.

A)a mixed lymphocyte reaction
B)the transfusion effect
C)kidney dialysis
D)ischemia
E)myeloablative therapy.

Question 61

Which of the following are correctly matched? (Select all that apply.)

A)hyperacute rejection: preexisting antibodies against cell-surface antigens
B)acute rejection: anti-HLA antibodies
C)chronic rejection: alloreactive T-cell clones specific for HLA allotypes of donor
D)acute rejection: direct pathway of allorecognition
E)transfusion effect: indirect pathway of allorecognition.

Question 62

Alloantibody production after organ transplantation involves _____.

A)a mixed lymphocyte reaction
B)the indirect pathway of allorecognition by CD4 T cells
C)activation of regulatory CD4 T cells
D)the transfusion effect
E)a switch from a chronic to an acute state of organ rejection.

Question 63

Prednisone is a steroid used in transplantation that _____.(Select all that apply.)

A)binds to a cell-surface receptor and inhibits the function of
B)is combined with cytotoxic drugs to improve its efficacy
C)decreases the synthesis of
D)causes a decrease in production of inflammatory cytokines
E)can lead to bone demineralization as an unwanted side-effect.

Question 65

The extent to which an individual's T cells respond to allogeneic HLA expressed on irradiated donor cells can be measured in vitro using _____.

A)a cross-match test
B)a superantigen recognition test
C)the mixed lymphocyte reaction
D)the transfusion effect assay
E)the panel reactive antibody test.

Question 66

The outcome of organ transplantation improves when _____.(Select all that apply.)

A)the patient has been transfused with blood sharing HLA allotypes with the transplanted organ
B)HLA-A,HLA-B and HLA-DR are matched
C)a thymectomy is performed at the time of transplantation
D)plasmapheresis is carried out before transplantation
E)immunosuppressive drugs are used to prevent the activation and proliferation of T cells.

Question 67

Effector mechanisms of _____ rejection resemble those responsible for type IV hypersensitivity reactions.

A)xenogeneic
B)acute
C)chronic
D)hyperacute
E)blood transfusion.

Question 68

Patients who have previously received a blood transfusion that has HLA-DR allotypes in common with their kidney transplant are _____.

A)less likely to reject the graft owing to the presence of regulatory CD4 T cells
B)more likely to reject the graft owing to the presence of HLA alloantibodies
C)less likely to reject the graft owing to negative selection of alloreactive T-cell clones
D)at risk of developing a hyperacute rejection
E)at risk of developing graft-versus-host disease.

Question 69

In a mixed lymphocyte reaction the donor cells are irradiated to ensure that they do not _____.

A)stimulate recipient cells
B)become anergic
C)alter their level of expression of HLA molecules
D)proliferate
E)undergo apoptosis.

Question 70

As the number of expressed MHC isoforms in the thymus increases beyond a certain value,the T-cell repertoire _____.

A)becomes smaller
B)becomes more diverse
C)is unaffected.

Question 71

Acute rejection of a kidney graft involves the activation of recipient T cells by _____ of _____ origin.

A)dendritic cells; recipient
B)B cells; recipient
C)dendritic cells; donor
D)macrophages; recipient
E)B cells; donor.

Question 72

_____ decreases the activity of the transcription factor NFAT by inhibiting calcineurin.(Select all that apply.)

A)Tacrolimus
B)Azathioprine
C)Mycophenolic acid
D)Cyclosporin A
E)Rapamycin.

Question 73

When donor MHC:donor self-peptide complexes activate recipient T cells,_____.

A)acute rejection of transplanted organs occurs
B)suppression occurs and transplanted organs are tolerated
C)hyperacute rejection of transplanted organs occurs
D)complement pathways are activated
E)an indirect pathway of allorecognition occurs.

Question 74

In chronic rejection,effector T cells respond to _____ complexes on _____-derived dendritic cells.

A)donor MHC class I:donor self peptide; donor
B)donor MHC class II:donor self peptide; donor
C)recipient MHC class I:donor MHC peptide; recipient
D)recipient MHC class II:donor MHC peptide; recipient
E)recipient MHC class II:donor MHC peptide; donor.

Question 75

_____ is a nitrogen mustard compound converted to a DNA-alkylating agent in the body that is used to inhibit cell proliferation after transplantation.

A)Methotrexate
B)Rapamycin
C)FK506
D)Cyclophosphamide
E)Mycophenolate mofetil.

Question 76

Steroid receptors are complexed with _____.

A)Hsp90 in the cytoplasm
B)Hsp90 on the cell surface
C)calcineurin in the cytoplasm
D)calcineurin in the nucleus
E)NFκB in the cytoplasm.

Question 77

Which of the following human molecules would be candidates for genetic modification of pigs to make these animals more suitable as organ donors for humans? (Select all that apply.)

A)membrane co-factor protein (MCP)
B)decay-accelerating factor (DAF)
C)HLA class II
D)HLA class I
E)CD59.

Question 78

A characteristic of the human eye that enables the cornea to be transplanted with a 90% success rate is that _____.(Select all that apply.)

A)antigen-presenting cells in the eye do not express the co-stimulatory molecule B7
B)the cornea is not vascularized
C)anterior-chamber-associated immune deviation (ACAID)establishes a state of tolerance in the eye
D)only regulatory T cells express the adhesion molecules necessary to enter the cornea
E)the aqueous humor of the anterior chamber contains TGF- $\beta$ ,which downregulates CD40 and inhibits IL-12 secretion.

Question 79

Which of the following is an effect of both tacrolimus and corticosteroids?

A)reduced T-cell proliferation
B)decreased production of nitric oxide
C)decreased production of IL-3,IL-4,GM-CSF,and TNF- $\alpha$
D)decreased activity of cyclo-oxygenase type 2
E)serum sickness.

Question 80

What is the probability that a sibling will be able to provide a HLA-haploidentical kidney for transplantation?

A)100%
B)75%
C)50%
D)25%
E)0%.