Transplant Immunology Flashcards

1
Q

Two types of tests to perform before transplantation?

A

Compatibility (HLA)

Pathogens (HIV, Hep, Herpes, Syph)

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2
Q

What is an autograft?

A

Transplantation of self tissues to a different site on the body

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3
Q

What is a syngeneic transplant?

A

Transplant between genetically identical individuals

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4
Q

What is an allogenic transplant?

A

Transplant btw two genetically different individuals

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5
Q

What is a xenograft

A

Transplantation between different species

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6
Q

Cause of Allogenic immune responses?

A

Genetic Differences between how and recipient

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7
Q

Describe what happens in a hyperacute (immediate) reaction

A

Preexisting Abs to A/B antigen or MHC I/II in recipients bind endothelial cells of transplanted organs. Rejection.

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8
Q

What would cause a hyperacute reaction to MHC I/II?

A

Pregnancy, Blood Transfusion, or previous transplantation

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9
Q

A type A antigen ends in….

A type B antigen ends in…

A
A = GalNAc
B = Gal
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10
Q

Name for the three rhesus factors we discussed?

A

C, D, E

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11
Q

Acute Rejection is…

A

Within Weeks
Effector CD4 TH1 Cells or CD8
Response to HLA differences between donor/recipient

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12
Q

How can acute rejection be prevented?

A

Immunosuppressive Drugs

anti-T cell antibodies

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13
Q

How does accelerated acute rejection (within days) happen?

A

Sensitized (memory) T cells from previous grafts/exposure

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14
Q

How does cross-reactive recognition for alloreactivity happen?

A

T cell recognizes an allogenic MHC molecule whose structure resembles the self MHC-foreign peptide complex.

Acute response to graft

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15
Q

Describe the process of T cell mediated graft rejection.

A

Donor Dendritic cells to the spleen
Activate recipient T cells
Graft Rejection

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16
Q

Describe the MLR (Mixed Lymphocyte Reaction) Test

A

Co-culture blood from donor and recipient. If theres a lot of proliferation or T cell mediated toxicity – its not a great match.

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17
Q

Describe chronic rejection

A

Months or Years after transplant
Thickening of BV walls –> Ischemia

Unclear Mech, Maybe Chronic DTH

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18
Q

In kidney transplant, it is especially important to match…

A

HLA A, B, DR

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19
Q

Describe the role of Minor Histocompatibility antigens in immune response

A

Minor HC are peptides are deriver from non-HLA I or II bodies. These are normally digested by the proteasome.

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20
Q

What three things must be true for GVHD to occur?

A

Graft must contain immunocompetent cells (T cells)
MHC Mismatch
The recipient must be incapable of rejecting the graft

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21
Q

How does GVHD happen?

A

Allogenic bone marrow transplant with mature T cells is transferred in. T cells circulate in the blood to secondary lymphoid tissues, where alloreactive T cells interact/proliferate. Effector CD4 and CD8 T cells enter tissues inflamed by the conditioning regimen.

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22
Q

Three potential cons of GVHD

A
  1. Donor-derived lymphocytes attack host tissues
  2. Non-functional T cells due to MHC mismatch
  3. Failed reconstitution
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23
Q

Alternative BMT sources to minimize GVHD.

A

Autologous BMT: Use self marrow obtained before radiation
Umbilical cord blood cells (w/ hematopoetic stem cells)
Isolated stem cells free of T cells

24
Q

Explain how NK cells can mediate a graft versus leukemia response

A

Haploid transplant in which one of the two HLA-C ligands matches. Donor hematopoetic cells safe from NK cells, but recipient cells (including any spare leukemia) are killed by NK.

25
Q

What happens at the stages of GVHD progress

A

Increasing macropapular rash, eventually erythroderma, and blistering.
Increasing serum bilirubin
Increasing Diarrhea and abdominal pain

26
Q

Problems with xenotransplantation (3)

A
  1. Humans have Ab to pig endothelial carbohydrates
  2. Pig cells are attacked by complement
  3. Zoonosis
27
Q

Potential solutions to xenotransplant problems.

A

Make transgenic cells expressing human DAF

Germ free or antigen free Pigs

28
Q

Advantage of xenograft strategy?

A

MHC molecules of different species are so different from those of humans so that T cells can not recognize them

29
Q

Four types of Immunosuppresive drugs listed for transplant/autoimmune disease?

A

Corticosteroids
Cytotoxic drugs that kill prolif. lymphocytes
Microbial immunosuppresive products
Immunosuppresive antibodies

30
Q

What do you do with immunosuppressants as time passes with the graft.

A

As immune system accomodates the graft, the dose of drugs is reduced

31
Q

Target of Cyclosporin/Tacrolimus?

A

Calcineurin

32
Q

Use of anti-CD52?

A

IgG binds to leukocytes to deplete them before organ transplantation

33
Q

Effect of treatment with corticosteroids (prednisone)

A

Induces expression of anti-inflammatory genes

Includes IkB-alpha that inhibits NF-Kb

34
Q

Side effects of steroids

A

Fluid retention, weight gain, diabetes, loss of bone mineral, thinning of the skin

35
Q

Effect of steroids on Prostaglandins? Leukotrienes?

A

Decreases them

36
Q

Annexin/Lipocortins act to…

A

Suppress Phospholipase A2

37
Q

Action of Cyclosporine

A

A cyclic decapeptide from a soil fungus

Targets calcineurin and blocks NFAT activation

38
Q

Action of FK506

A

A macrolide isolated from a soil actinomycete

Targets calcineurin and blocks NFAT activation

39
Q

Significance of blocking NFAT activatyion

A

Suppresses T cell activity

40
Q

What does Rapamycin do?

A

It is a macrolid isolated from a soil bacterium

Blocks mTOR signal transduction required for proliferation.

41
Q

Overall Function of… Cyclosporine and FK506

A

Blocks T cell cytokine production by inhibiting activation of NFAT transcription factor

42
Q

Overall Function of…Rapamycin

A

Blocks lymphocyte proliferation by inhibiting IL2 signalling

43
Q

Overall Function of…Corticosteroids

A

Reduce inflammation by inhibiting macrophage cytokine signalling

44
Q

Overall Function of…anti-CD3 monoclonal antibody

A

Depletes T cells by binding to CD3 and promoting phagocytosis or complement-mediated lysis

45
Q

Anti-CD3 monoclonal antibody is commonly used to….

A

treat acute rejection

46
Q

What type of kinase activated Calcineurin?

A

Serine/Threonine Kinase

47
Q

NFAT is directly inhibited by

A

CsA-CyP or tacrolimus-FKBP

48
Q

Cyclosporine A and FK 506 are important in activation of…

A

T cells, B cells, and Granulocytes

49
Q

Three listen cytotoxic drugs?

A

Azathioprine
Cyclophosphamide
Methotrexate

50
Q

How does azathioprine work?

A

Inhibits DNA replication, kills not only lymphocytes but also all dividing cells in the body.

51
Q

How does cyclophosphamide work?

A

Cross-link DNA

Side Effect - Damage to Bladder

52
Q

How does Methotrexate work?

A

Prevents DNA replication by inhibiting thymidine synthesis

53
Q

Biggest problem with using cytotoxic drugs?

A

Specificity issues

54
Q

Limitations of the use of Antibodies against human T cells

A

Non-human antibodies can induce immune reactions that remove them

55
Q

Summary – Cause of….

Hyperacute, Accelerated Accute, Acute, Chronic Rejection

A

Hyperacute – preexisting antibodies to ABO and other antigens
Accelerated Acute – Preexisting Memory T cells
Acute – MHC compatability, T cells
Chronic – Blood vessel wall thickening

56
Q

What type of rejection is GVHD

A

Acute

57
Q

Immunosuppressive drugs suppress the _____ rejection process

A

Acute

but they also slow down the chronic