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Pathology by week > W15 - Transplantation > Flashcards

W15 - Transplantation Flashcards

1
Q

What is the range of half-life for adult kidney transplants?

List the following from highest to lowest half life:

  • Living donor (1-year conditional survival)
  • Living donor
  • Deceased donor (1-year conditional survival)
  • Deceased donor
A

Half life ranges from 10-15 years

Living donor (1-year conditional survival) > living donor > deceased donor (1-year conditional survival) > deceased donor

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2
Q

Name 3 ways to improve transplant outcome?

A
  1. Improved surgical technique
  2. Improved pre- and post-transplant patient management
    - Drug levels, infections, CVS disease, diabetes, etc.
  3. Better understanding of transplant immunology
    - Prevention, diagnosis + treatment of graft rejection

END RESULT => improved patient survival and graft survival!

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3
Q

Describe phase 1 to phase 3 of immune response to transplanted graft

A

Phase 1 = recognition of foreign antigens

Phase 2 = activation of antigen-specific lymphocytes

Phase 3 = effector phase of graft rejection

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4
Q

What are the 2 protein variations in clinical transplantations that are important?

A
  1. ABO blood group
  2. HLA (Human Leukocyte Antigens)
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5
Q

What are the 2 major components to organ rejection?

A
  1. T cell-mediated rejection
  2. Antibody-mediated rejection (B cells)
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6
Q

Describe HLA class I and II - where are they expressed?

A

HLA class I (A, B, C) => on ALL cells

HLA class II (DR, DQ, DP) => on APCs, but can also be upregulated on other cells under stress

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7
Q

HLA classes are highly _________, meaning that there are hundreds of _____ for each locus.

A

HLA classes are highly polymorphic, meaning that there are hundreds of alelles for each locus.

ex: A1, A2, A3 => A372 and up

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8
Q

What is the important interaction in T cell mediated rejection?

A

T cell TCR interacts with highly vairable HLA with its antigen => interaction => T cell becomes ACTIVATED!

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9
Q

Which 3 HLA are used for matching donor and recipients in organ transplantation?

A

HLA-A

HLA-B

HLA-DR

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10
Q

How are HLA mismatches written?

What is the max # of HLA mismatches?

A

For example: 1:1:0

(in the order of HLA-A, HLA-B, HLA-DR)

max 6 mismatches

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11
Q

Minimising HLA differences between donor and recipient improves transplant outcome - T or F? explain

A

True - The more mismatches you have the worse the outcome

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12
Q

In terms of HLA matching for organ transplantation, explain chances of MM for A) parent to child and B) sibling to sibling

A

A) Parent to child

>=3/6 MATCHED

B) Sibling to sibling

25% - 6 MM

50% - 3MM

25% - 0MM

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13
Q

How does HLA disparity cause rejection?

A
  1. T cell mediated
  2. Antibody mediated
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14
Q

A lot of the immunosuppressive medications developed to use for transplanted organs target T cell activation. Name 4 targets for these drugs. Give drug names for each.

A
  1. block calcineurin involved in downstream signalling of TCR = calcineurin inhibitors (tacrolimus)
  2. block MTOR signalling = Siromilus or steroids
  3. block cytokine signalling = anti-CD25 antibodies
  4. blocks TCR = OKT3 (used in acute rejection!)
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15
Q

Describe the 3 steps to T cell mediated rejection

A
  1. T cell - APC interaction
  2. T cell activation, inflammatory cell recruitment
  3. effector phase (organ damage) = cytotoxic T cells and monocyte/macrophages will tether, roll, arrest, and diapedesis into the endothelium of the graft = interstitial inflammation = tubulitis
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16
Q

Describe the 3 phases of antibody-mediated rejection

A

Phase 1 - B cells recognise foreign HLA

Phase 2 - Proliferation and maturation of B cells with anti-HLA abs production

Phase 3 - Effector phase; antibodies bind to graft endothelium = INTRA-VASCULAR DISEASE

17
Q

What does this histo slide show in terms of rejection in transplanted solid organ?

A

Arteritis

macrophages under the epithelial layer = likely T cell mediated rejection

19
Q

What do you see in this histo slide of a transplanted kidney?

A

right circle = lots of immune cells stuck in glomerulus = glomerulitis

left circle = lots of immune cells stuck there = capillaritis

=> ab-mediated rejection

20
Q

antibody mediated rejection of transplanted, solid organs happens _______

A

intravascularly

22
Q

anti-HLA antibodies are/are not naturally occuring, anti-A or anti-B antibodies are/are not naturally occuring?

A

anti-HLA antibodies ARE NOT naturally occuring, anti-A or anti-B antibodies ARE naturally occuring

23
Q

Pre-formed anti-HLA abs = give 3 examples where they arise from?

A
  1. Previous transplantation
  2. Pregnancy
  3. Transfusion
24
Q

A and B glycoproteins - where do you find them in donor organ?

A

Donor RBCs

endothelial lining of blood vessels in transplanted organ

25
Q

Group A

Group B

Group AB

Group O

What abs does each have in their plasma?

A

Group A = anti-B

Group B = anti-A

Group AB = none

Group O = Anti-A, anti-B

26
Q

Describe 3 times when screening for anti-HLA abs is done

A
  1. Before transplantation
  2. At time of transplantation
  3. After transplantation
27
Q

Name and briefly describe 3 types of assays used for screening for anti-HLA abs

A
  1. Cytotoxicity assays = does recipient serum kill donor lymphocyte in prescent of complement = lymphocytes remain viable if NO ab binding
  2. Flow cytometry = does recipient serum bind to donor lymphocyte (using IF labelled anti-human Ig)
  3. Solid phase assays = does the recipient serum bind to recombinant single LA molecules attached to a solid support such as beads?
28
Q

Give a few drugs that inhibit ab-mediated rejection of transplanted organs

A
  1. Remove abs with plasma exchange
  2. Intravenous Ig
  3. Anti-CD40/anti-CD20
  4. BAFF inhibitors
  5. Proteosome inhibitors
29
Q

How do you detect rejection in kideny transplant?

A
  1. Monitor transplant function (creatinine) => if creatinine becomes elevated, take biopsy to cofnirm and classify rejection
  2. screen for antibodies
30
Q

Describe treatments for T cell and ab-mediated kidney rejection

A

T cell => steroids (methylprednisolone), OKT3/ATG

ab-mediated => IVIG, plasma exchange, anti-CD20

31
Q

What agents are used as induction agents (3) and baseline immunosuppression (3) for kidney transplant

A

Induction agent

  1. OKT3/ATG
  2. anti-CD52
  3. anti-CD25 (anti-IL2R)

Baseline immunosuppression

  1. CNI inhibitor +
  2. MMF or Aza
  3. with or without steroids
32
Q

The most important antigenic determinant of rejection in current clinical practice for kidney transplantation is…

A) ABO blood group

B) Human Leukocyte Antigen/Major Histocompatibility Complex

C) Minor Histocompatibility Complex

A

B) Human Leukocyte Antigen/Major Histocompatibility Complex

33
Q

A potential donor is described as being 1:1:0 MM. What does this mean?

A

1 MM A locus; 1 MM B locus; 0 MM DR locus

34
Q

The main effector cells (2) in T cell mediated rejection are…

A

T cells (mainly cytotoxic) and monocyte/macrophages

35
Q

A patient has an episode of acute T cell mediated rejection 2 months post-transplantation. What additional drug would most commonly be administered?

A

Steroids - methylprednisolone

36
Q

Whih cell is injured in the effector phase of ab-mediated rejection of transplanted kidney?

A

Endothelial cells

(Remember, it’s INTRAVASCULAR damage)

Pathology by week (70 decks)

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