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ABBEY MSII Unit 5 > Micro Transplants > Flashcards

Micro Transplants Flashcards

1
Q

what are the most critical antigens to match in transplantation?

A

blood groups

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2
Q

what are the three major classes of rejection

A

hyperacute, acute, chronic

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3
Q

what is a potential problem when bone marrow is transplanted?

A

graft T-cells react with host tissues (graft vs host disease) - need to remove T-cells from transplant

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4
Q

hyperacute rejection

A

most severe and immediate type of rejection caused by preformed antibodies that react to the transplanted organ - MC is blood group antigen
can also have pre-existing antibodies against HLA-antigens

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5
Q

what is a way that pre-existing antibodies against HLA-antigens can be formed already?

A

past blood transfusion - other person’s WBC could already be making those antibodies

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6
Q

graft rejection when blood group antigens don’t match

A

pre-existing antibodies against donor blood group antigens, antibodies bind vascular endothelium of graft, initiating an inflammatory response that occludes blood vessels -> graft becomes engorged and purple-colored because of hemorrhage causing graft failure

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7
Q

what is the panel reactive antibodies?

A

serum of a recipient is tested against a panel of leukocytes and determines the presence of antibodies to HLA - presented as a percentage from 0-100%

  • low value = antibody against a few individuals
  • high value = high likelihood that patient will have antibodies against potential donor tissue
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8
Q

antibodies to paternal HLA - problems for pregnancy

A

trauma of birth exposes maternal circulation to fetal cells and stimulates the production of antibodies against paternal HLA - future pregnancies at risk

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9
Q

acute rejection

A

T-cells from the recipient become reactive against the transplant - takes days to weeks

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10
Q

what are most rejections due to MHC focused on?

A

class I mismatches which lead to CD8+ cells killing transplanted cells

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11
Q

what are the two mechanisms of acute rejection?

A
  1. stronger response: response to donor cells expressing class II MHC
  2. activated CD8+ lymphocytes kill based on MHC class I mismatches
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12
Q

mechanism by which kidney graft destroyed by effector T cells

A

dendritic cells from kidney graft migrate tot eh spleen where the activate effector T cells, and then effector T cells migrate to graft via blood

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13
Q

HLA class I isotypes

A

HLA-A, B, C, E, F, G

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14
Q

HLA class II isotypes

A

HLA-DM, DO, DP, DQ, DR

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15
Q

what is direct allorecognition?

A

both CD4 and CD8 positive cells are stimulated at the same time

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16
Q

chronic rejection

A

takes months to years - the result of indirect recognition of the transplant (only CD4 or minor antigens)

17
Q

what is chronic rejection often associated with?

A

the presence of antibodies to HLA-class I antigens in the graft which act on the vasculature - increasing damage to vessels

18
Q

what testing is done to make transplants work?

A
  1. blood type (ABO)
  2. HLA I and II
  3. panel reactive antibody
  4. find match on computer net
  5. cross match on all positive sera from antibody screening
  6. mixed lymphocyte reaction
  7. molecular techniques
19
Q

what does the mixed lymphocyte reaction measure?

A

the ability of recipient cells to respond to donor MHC antigens (proliferation vs cytotoxicity)

20
Q

what gives rise to minor histocompatibility antigen differences between donor and recipient

A

polymorphic self proteins that differ in amino acid sequence between individuals

21
Q

how is rejection prevented?

A

induction of immunosuppression at time of transplant

  1. inducing sever immunosuppression at the time of transplant
  2. antilyphocyte globulin (ALG or ATG)
  3. monoclonal antibodies
  4. belatacept (CTLA4-IG)
22
Q

antilymphocyte (thymocyte) globulin (ALG or ATG)

A

a preparation that contains antibodies raised in rabbits or horses directed against T cells

23
Q

monoclonal antibodies used in prevention of rejection

A
  1. muromonab-CD3 - (anti-CD3) - bind CD3 molecule on surface of T cells and eliminates T cells
  2. daclizumab and basiliximab target IL-2 (CD25) inhibiting only activated T cells
24
Q

belatacept (CTLA4-IG)

A

a protein produced by recombinant DNA technology that combines the extracellular portion of CTLA4 - ligand for B7 - with the Fc region of the human IgG1 antibody, blocking co-stimulation of T-cells

25
Q

what are used for life long maintenance treatments?

A

maintenance drugs

  1. corticosteroids - interfere with transcription factor needed to turn on the genes for T cells to become activated - usually use prednisone and prednisolone
  2. cytotoxic drugs
  3. FK506 and cyclosporine
26
Q

cytotoxic drugs in life long maintenance treatments

A

interfere with DNA synthesis - interfere with the rapid cell proliferation needed for immune responses
-azathioprine (purine analog) - MC use mycophenolic acid

27
Q

FK506 and cyclosporine in life long maintenance treatments

A

naturla products isolated from microbial cultures - inhibit the calcineurin signaling pathway used by T cells to turn on their genes for activation (IL-2 secretion)

  • FK506 = prograf
  • cyclosporine = neoral
28
Q

grade I tissue reaction for graft vs host

A
  • maculopapular rash on less than 25% of body surface
  • serum bilirubin 2-3 mg
  • more than 500 ml diarrhea per day
29
Q

grade II tissue reaction for graft vs host

A
  • maculopapular rash on 25-50% body surface
  • serum bilirubin 3-6 mg
  • more than 1000 ml diarrhea per day
30
Q

grade III tissue reaction for graft vs host

A
  • generalized erythroderma
  • serum bilirubin 6-15 mg
  • more than 1500 ml diarrhea per day
31
Q

grade IV tissue reaction for graft vs host

A
  • generalized erythroderma with bullous formation and desquamation
  • serum bilirubin at 15 mg
  • severe abdominal pain with or without ileus
32
Q

graft vs host disease is most likely to happen with?

A

class I and II mismatch, and class II mismatch

33
Q

lowest survival long term is associated with what?

A

class I and II mismatch and multiple class I mismatch

ABBEY MSII Unit 5 (8 decks)

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