Immunology 3 - Transplantation Flashcards

(30 cards)

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 (Ch6 HLA)
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3
Q

On which type of cell is HLA class I (A/B/C) expressed?

A

All cells

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4
Q

On which type of cell is HLA class II (DR/DQ/DP) expressed?

A

Antigen-presenting cells

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5
Q

Which types of HLA fall into each class?

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

Most impt - DR>B>A

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6
Q

Which part of the HLA molecule is highly variable?

A

peptide binding grove - allows us to present variety of Ag to immune cells

HLA I - ⍺1+⍺2

HLA II - ⍺1

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7
Q

In T cell-mediated transplant reaction, how are alloreactive T cells activated (phase 1)?

A
  1. Presentation of foreign HLA antigens in MHC by APCs (both DONOR and HOST APC cells are involved)

Direct - donor APC present Ag to T cells (mainly acute rejection)

Indirect - recipient APC presents donor Ag to T cells (mainly chronic)

  1. Costimulatory signals

occurs in lymph nodes

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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

How does T cell mediated rejection result in graft damage

A

Cytotoxic T cells: granzyme B, perforin, Fas-ligand

Macrophages: phagocytosis, proteolytic enzymes, cytokines, O2/N2 radicals

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10
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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11
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 tubular epithelium)

Macrophages, recruited by T cells

arteritis

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12
Q

What are some examples of drugs targeting T cell rejection?

A
  • Steroids
  • Inhibitors of cell signalling / Calcineurin inhibitors (i.e. Tacrolimus, Cyclosporine)
  • Anti-proliferative agents (i.e. Mycophenolate mofetil, Azathioprine)
  • Inhibitors of cell surface receptors (i.e. Anti-CD3 antibody (OKT3), ATG / Anti-thymocyte globulin)
  • Alemtuzumab: anti-CD52 monoclonal antibody that causes lysis of T cells
  • Basiliximab: anti-CD25 monoclonal antibody which targets IL-2-R → less proliferation
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13
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 (intravascular disease)
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14
Q

Recall the process of antibody-mediated rejection phase 3

A

Abs bind HLA on graft vacular endothelium –> complement activation to form MAC and inflammatory cell recruitment

endothelial injury and inflammation (capillaritis)
Capillaritis is a cardinal feature of antibody-mediated rejection

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15
Q

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

A
  • Capillaritis = inflammatory cells in capillaries of the kidney → injury
  • also procoagulant tendencies and closure of microcirculation → graft fibrosis
  • Immunohistochemistry shows fixation or complement fragments on endothelial cell surfaces
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16
Q

What is the main difference between T cell and B cell mediated rejection?

A

T cells = interstitial damage, B cells = endothelial damage

17
Q

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

A

PCR-DNA sequencing

NOTE: mismatch positive transplantation CAN take place, but requires a lot of preparation (plasma exchange and IVIG)

18
Q

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

A
  1. Cytotoxicity assays - does recipient serum kill donor’s lymphocytes? (+ve crossmatch → cell lysis (i.e. +ve is bad)
  2. Flow cytometry - does recipient’s serum bind donor’s lymphocytes? looking for BOUND FLUORESCENTLY-LABELLED ANTIBODY
  3. Solid phase assays, beads contain all possible HLA phenotypes - fluorescent Ig to determine which HLA epitopes bind Abs
19
Q

What is the most reliable HLA test nowadays?

A

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

20
Q

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

A

Induction agent + baseline immunosuppression

21
Q

What are some examples of baseline immunosuppression for transplants?

A
  • Mycophenalate mofetil/azathioprine
  • Tacrolimus (calcineurin inhibitor)
  • +/-Prednisolone
  • (Pre-Transplant Meds = acronym)

(impt - come up)

22
Q

What are some examples of induction agents in transplant immunosuppression?

A

T cell depleting - OKT3/ATG, anti-CD52

anti- IL2 R

23
Q

How would you nonitor transplant function?

A

creatinine

if ↑creatinine - take biopsy and classify rejection

24
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

Corticosteroids - pred

ATG/OKT3

25
How would you treat Ab mediated acute rejection?
IVIG (reduce Ab prod -ve feedback, displaces troublesome Abs so they cannot exert harmful effect) plasma exchange anti-C5/CD20
26
Recall 3 pathologies that immunosuppresion increases risk of
Infection (BK) malignancy (PTLD, viral associated (EBV/HHV8 Kaposi/skin) drug toxicity (CNI, nephrotoxicity) recurrent glomerulonephritis
27
What is this showing and when can it occur?
arterial wall thickening post transplant needs BP control/vacular stent
28
What is the post-transplant risk of malignancy?
Viral-associated malignancies are much more common, such as: - Kaposi sarcoma (HHV8) - Lymphoproliferative disease (EBV) Skin cancer is 20x more common
29
how would you code these mismatches?
1:1:0 = 2MM (max 6)
30
Which HLA subtypes are most important to match?
DR \> B \> A