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Leila's Yr 5 Pathology > Immunology 5 - Transplantation > Flashcards

Immunology 5 - Transplantation Flashcards

1
Q

Average half life of a donated kidney

A

9-14 years (12)

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2
Q

The most relevant protein variations in clinical transplantation are…

A

ABO blood group

HLA

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3
Q

Which chromosome is HLA coded on?

A

Chromosome 6

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4
Q

The two major forms/components of rejection

A

T-cell mediated and antibody-mediated rejection

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5
Q

3 phases ofimmune response to transplanted graft

A

Phase 1 = recognition of foreign antigens
phase 2 = activation of antigen-specific T lymphocytes
Phase 3 = effector phase of graft rejection

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6
Q

In transplant, which HLA alleles are most important to match?

A

DR > B > A

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7
Q

What is a major determinant of the risk of rejection

A

The number of HLA mismatches

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8
Q

Number of alleles shared between parent: child and siblings

A

Parent to child: 50% alleles shared

Siblings: 25-50%

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9
Q

Phase 1 of T-cell mediated rejection

A

1) Presentation of foreign HLA antigens in MHC by APCs (both DONOR - direct and HOST - indirect) - aPC:TCR reaction
2) Co-stimulation
3) Amplification and activation through cytokine release

These actions occur in the lymph nodes

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10
Q

Phase 2 of T-cell mediated rejection (actions of activated T cells)

A 
Proliferation
Production of cytokines (IL-2 important)
Provide help to CD8+ T Cells
provide help for antibody production
recruit phagocytic cells
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11
Q

Phase 3 (effector phase) of T-cell rejection

A

The T cells will tether, roll and arrest on the endothelial cell surface
THey will then transmigrate through the interstitium and start attacking the TUBULAR EPITHELIUM

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12
Q

Effect of cytotoxic T cells inside the transplanted organ

A

Granzyme b, perforin, Fas ligand

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13
Q

Histological features of T cell mediated rejection

A

Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubulitis
(can also get arteritis if the inflammatory cells attack the blood vessels)

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14
Q

A fail in graft function is not always due to rejection, what else could it be caused by?

A

Immunosuppressants given post transplant can be nephrotoxic, just need to adjust dose

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15
Q

Which type of recognition in acute rejection and chronic rejection, respsectively

A

Acute: direct (donor APC presenting antigen to recipient T cells)
Chronic: indirect (Recipient APC presenting antigen to recipient T cells)

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16
Q

Cardinal feature of antibody mediated rejection

A

CAPILLARITIS = inflammatory cells in the capillaries of the kidneys

17
Q

Phase 3 - effector phase of antibody mediated rejection

A

Antibodies bind to graft endothelium

18
Q

Are anti-HLA anitbodies naturally occuring?

A

No

19
Q

How can anti-HLA antibodies be formed?

A

Pre-formed: pregnancy, transplant, transfusion

Post-formed

20
Q

What does antibody mediated rejection eventually result in?

A

Graft fibrosis

21
Q

How can you tell if graft is being rejected?

A

Raising creatinine and biopsy

22
Q

Methods to prevent graft rejection

A

HLA typing via PCR DNA sequencing

Screening for anti-HLA antibodies before, during and after transplant

23
Q

3 assays to screen for anti-HLA antibodies

A 
Cytotoxic assays (cdc)
Flow cytometry (Facs)
Solid phase assays (luminex - series of beads containing all the possible HLA epitopes)
24
Q

There are 3 signals to activate T cells and they can all be targeted as immunosuppresion

A

APC MHC to TCR
APC CD80/86 to T cell CD28 (Costimulation)
CYtokines IL-2 to T cell CD25

25
Q

A drug commonly given to prevent T-cell mediated rejection

A

Steroid

26
Q

Inhibitor of cell signalling

A

Calcineurin inhibitor e.g. tacrolimus

27
Q

Anti-proliferative agents

A

Mycophenolate mofetil, azathioprine

28
Q

Inhibitors of cell surface receptors

A

anti-CD3 antibody (OKT3), ATG

29
Q

Alemtuzumab, function

A

anti CD52 mab –> T cell lysis

30
Q

Basiliximab and daclizumab, function

A

anti-CD25 mab which targets IL2R –> less T cell proliferation

31
Q

Baseline immunosuppression regimen

A

CNI + MMF/Aza +/- steroids

32
Q

Induction agents

A

OXT3/ATG (AntiCD3)/ Anti-CD52, Anti-CD25 (gievn at time of or just before transplant to prepare)

33
Q

Mx of acute cellular rejection

A

steroids, OKT3/ATG

34
Q

Mx of acute Ab-mediated rejection

A

IVIG, plasma exchange, anti-C5, anti-CD20

35
Q

Drug targets of antibdoy mediated rejection

A 
Rituximab (antiCD20)
BAFF inhibitors (target cytokines that promote B cell growth)
Proteasome inhibitors (bortezomib) block antibody production by plasma cells
36
Q

GVHD symptoms (Days-weeks)

A 
Nause+vomiting
Rash
abdo pain
diarrhoea/bloody
jaundice

Leila's Yr 5 Pathology (100 decks)

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