Immunology 3 - Transplantation Flashcards

1
Q

Recall the 3 phases of immune response to a transplanted graft

A
  1. Recognition of foreign antigens
  2. Activation of antigen-specific lymphocytes
  3. Effector phase of grant rejection
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2
Q

What are the 2 most variant protein variants in clinical transplantation?

A

ABO blood group

HLA antigens

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3
Q

On which type of cell is HLA class I expressed?

A

All cells

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4
Q

On which type of cell is HLA class II expressed?

A

Antigen-presenting cells

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5
Q

Which part of the HLA molecule is highly variable?

A

Peptide binding groove in between the alpha subunits

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6
Q

In T cell-mediated transplant reaction, how are alloreactive T cells activated?

A
  1. Both donor and host APCs present foreign HLA in MHCs

2. Costimulatory signals

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7
Q

Which types of HLA fall into each class?

A
HLA-A, B, C = class 1
HLA-DR, DQ, DP =class 2
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8
Q

What are the actions of activated T cells in T cell-mediated transplant rejection?

A
  1. Proliferation
  2. Produce cytokines (especially IL2)
  3. ‘Help’ CD8+ cells
  4. ‘Help’ antibody production
  5. Recruit phagocytic cells
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9
Q

What test can be used to see if transplant rejection is occurring?

A

A biopsy - an inflammatory response will be seen

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10
Q

What are the key histological features of T cell-mediated transplant rejection?

A

Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubulitis (inflammatory cells within the tubular epithelium)
Macrophages, recruited by the T cells

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11
Q

Recall the 3 phases of antibody mediated rejection

A
  1. B cells recognise foreign HLA
  2. Proliferation and maturation of B cells with anti-HLA antibody production
  3. Effector phase: antibodies bind to graft ENDOTHELIUM
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12
Q

Recall the process of antibody-mediated rejection phase 3

A

Antibody binding to transplanted organ vessel endothelium –> complement activation to form MAC and monocyte/neutrophil recruitment via Fc receptor –> endothelial injury and inflammation (capillaritis)
Capillaritis is a cardinal feature of antibody-mediated rejection

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13
Q

What are the key histological features of antibody-mediated transplant rejection?

A
  1. Inflammatory cell infiltrate
  2. Capillaritis
  3. Immunohistochemistry shows fixation or complement fragments on endothelial cell surfaces
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14
Q

Describe the effector phase of T cell-mediated transplant rejection

A

The T cells will tether, roll and arrest on the endothelial cell surface
They will then crawl through into the interstitium and start attacking the tubular epithelium

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15
Q

What test is used to do HLA typing before a transplant?

A

PCR-DNA sequencing

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16
Q

What at the 3 methods of screening for anti-HLA antibodies?

A
  1. Cytotoxicity assays - inspects if recipient’s serum binds to the donor lymphocytes by looking for LYSIS
  2. Flow cytometry - inspects if recipient’s serum binds to the donor lymphocytes by looking for BOUND FLUORESCENTLY-LABELLED ANTIBODY
  3. Solid phase assays, ‘Luminex’ (uses a series of beads that contain all the possible HLA phenotypes) - fluorescently labelled immunoglobulin used to determine which HLA epitopes the antibodies bind to
17
Q

What is the most reliable HLA test nowadays?

A

Solid phase assays - uses beads that have different HLA epitopes and fluorescent colour

18
Q

Recall 2 treatments that all transplant recipients receive to prevent rejection?

A
Induction agent
Base-line immunosuppression 
Baseline immunosuppression is important to learn (has been in PPQ) = 
Mycophenalate mofetil
Tacrolimus (calcineurin inhibitor)
Prednisolone
(Pre-Transplant Meds = acronym)
19
Q

A pt has an episode of acute T cell-mediated rejection 2 months post-transplantation. What would be the most common drug administered?

A

Corticosteroid (prednisolone)

20
Q

Recall 3 pathologies that immunosuppresion increases risk of

A

Infection, malignancy and drug toxicity

21
Q

Recall some drugs used to manage T cell vs antibody-mediated transplant rejection

A

T cell rejection management:

  • Steroids (prevent general T cell activation)
  • Calcineurin inhibitors (prevent cell signalling)
  • Anti-proliferative agents (mycophenalate, azothioprine)
  • receptor inhibitors (eg anti-CD3)

Antibody rejection management:

  • Rutiximab (anti-CD20)
  • BAFF inhibitors
  • proteasome inhibitors (block antibody production by plasma cells)
  • complement inhibitors (block complement binding to endothelium)
22
Q

What is the main complication of HSCT?

A

GvHD

23
Q

What is the pathogenesis of GvHD in HSCT rejection?

A
  1. During SCT, the host immune system is eliminated (total body irradiation and drugs)
  2. Bone marrow then replaced (allogenic/autologous)
  3. Allogenic SCT leads to reaction of donor lymphocytes against host tissues (related to a degree of HLA-incompatibility)
  4. If there is a malignancy, the graft can help kill these cells (graft-versus-tumour)
24
Q

What are the 2 options for GvHD prophylaxis before HSCT?

A

Methotrexate

Cyclosporine

25
Q

How should GvHD following HSCT be treated?

A

Steroids

26
Q

What are the symptoms of GvHD following HSCT?

A

A bit like a slow anaphylaxis with jaundice:

  • Rash
  • Nausea and vomiting
  • Abdominal pain
  • Diarrhoea/bloody stool
  • Jaundice
27
Q

What is the post-transplant risk of malignancy?

A

Viral-associated malignancies are much more common, such as:
- Kaposi sarcoma (HHV8)
- Lymphoproliferative disease (EBV)
Skin cancer is 20x more common