Imm - Transplantation Flashcards

1
Q

Which is the most commonly transplanted organs

A

1st most common transplanted organs = KIDNEYS (average ½ life of a kidney is 12 years)
2nd most common = LIVER

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2
Q

What are the phases of immune response to a transplanted graft

A

Phase 1: recognition of foreign antigens
Phase 2: activation of antigen specific lymphocytes
Phase 3: effector phase of graft rejection (cells cause injury to graft)

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3
Q

Which protein variations are most important for matching in transplantation

A
  1. HLA (Chr 6 by MHC) - DR > B > A
  2. ABO groups
  3. Others
    (minor histocompatibility genes)
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4
Q

What are the two major pathways of rejection and how do you tell between them

A

T cell or antibody mediated

Can only tell them apart with biopsy (both are acute with raised creatinine/CK)
T cell = responds well to treatment
Antibody - more difficult to treat

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5
Q

What are the number of HLA mismatches between family members

A

Parents/child: ≥3 always matched (all on one chromosome - can’t be <3)
Siblings: 25% 6MM, 50% 3MM, 25% 0MM

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6
Q

Describe T-cell mediated transplant rejection

A
  1. Presentation of the foreign HLA in MHC by APCs (BOTH donor and host APCs) in the lymph nodes
  2. Co-stimulatory signals → effector phase → inflammation → raised CK
  3. Proliferation and activation of CD4/8 → cytokine release (IL-2) → autocrine activation of T cells
  4. T cells tether, roll and arrest on the endothelial cell surface → migrates through the interstitium → tubular epithelium attack
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7
Q

What are the histological features of T-cell mediated rejection

A

Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubilitis (inflammatory cells within the tubular epithelium)
Macrophages
Creatinine rise

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8
Q

Describe antibody-mediated transplant rejection

A
  1. B cell exposure to foreign antigen
  2. Proliferation and maturation of B cells with Ab production
  3. Abs bind to HLA on the graft endothelium (capillaries of glomerulus and around the tubules) → INTRA-VASCULAR inflammation
    - Endothelial cell lysis
    - Inflammatory cell recruitment
    - CAPILLARITIS (mononuclear, NK and neutrophils in the capillaries)
  4. Pro-coagulation tendencies and closure of the microcirculation → graft fibrosis
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9
Q

What is the histology of antibody-mediated transplant rejection

A

Inflammatory cell infiltrate
Capillaritis (inflammatory cells in the microcirculation – a cardinal feature of antibody mediated rejection) - inflammatory cells seen within the vasculature, not in tubules
Immunohistochemistry: fixation of complement fragments on endothelial cell surfaces

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10
Q

How is HLA screened for transplantation

A

Before, at the time of, and after transplantation

HLA typing via PCR DNA sequencing (esp. for BM and kidney)
Anti-HLA Ab screening:
- Cytotoxicity assay: recipients serum against donor lymphocytes (+ve = cell lysis)
- Flow cytometry: recipients serum binds to donor lymphocytes
- Solid phase assay: recipient serum mixed with beads and labelled to determine with HLA epitopes the Abs bind to (highly sensitised = lots of Abs)

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11
Q

How is transplant rejection treated

A

T cell: steroids (IV 3x then oral) / OKT3/ATG
Antibody-mediated: IVIVg, Plasma exchange, anti-C5, anti-CD20 (Rituximab)

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12
Q

What is the immunosuppression regime for transplantation

A
  1. Induction of immnosuppression:
    - Anti-CD52 (alentuzumab)
    - Anti-CD25 (basiliximab)
    - OKT3/ATG
  2. Baseline immunsuppresssion:
    - Tacrolimus or ciclosporin
    - Steoirs
    - Azathioprine /mycophenolate mofetil
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13
Q

What are the types of time-dependent transplant reactions and what is the histology

A

Hyperacute = mins-hours (pre-formed Abs) → necrosis, thrombosis
Acute = < 6 months → cellular infiltrates (Cellular), vasculitis and C4 deficiency (Ab)
Chronic = >6 months → fibrosis, glomerulonephropathy, vasculopathy, Bronchiolitis obliterans (BOOP)

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