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Year 2 - MCD Immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

Why do we do transplantations?

A

(1) Save life
• other life-support methods not fully developed
• other methods at the end of their lives

(2) Enhance life
• other methods less good e.g. dialysis
• organ is nor vital but enhances life e.g. cornea

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2
Q

Why do organs fail?

A

For variety of reasons:
• cornea - degenerative disease/infection/trauma
• skin/composite - burn/trauma/infection/trauma

  • kidney - diabetes/HBP/glomerulonephritis
  • liver - cirrhosis/ acute LF
  • heart - etc.
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3
Q

What organs can be transplated?

A 
Cornea
Skin
Bone marrow
Kidney
Liver
Heart
Lungs
Pancreas
Small bowel
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4
Q

Types of transplantations?

A
  1. Autografts
    • within same individual
    • e.g. coronary artery bypass
  2. Isografts
    • between genetically identical individuals of same species
  3. Allografts
    • between diff. individuals of the same species
  4. Xenografts
    • betw. individuals of diff. species
    • e.g. heart valves & skin
  5. Prosthetic graft
    • plastic, metal
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5
Q

Types of donors for allografts?

A

Deceased donor

vs.

Living donor

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6
Q

Explain deceased donors

A

DBD - Deceased Brain-Death
• heart is beating
• COOL DOWN to minimise ischaemic damage

DCD - Deceased Cardiac-Death
• heart NOT beating
• longer period of warm ischaemia time
• suitable for kidney transplant

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7
Q

What needs to excluded for deceased donors before they can be used?

A

Viral infection (HIV, HBV, HCV)

Malignancy

Drug abuse, OD, poison

Disease of the transplated organ

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8
Q

What happens to the organs after they are removed?

A

Rapidly cooled & perfused
• max. cold ischaemia for kidneys if 60hr (shorter for other organs)
• cornea exception @ 96hrs

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9
Q

Transplant selection?

A

For access to WAITING LIST

x Refer for assessment
x MDT asses eligibility
x NHS transplant list
x Inspect contraindications

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10
Q

Transplant allocation?

A

For ACCESS to an ORGAN

NHSBT montiors allocation
• uses national guidelines & algorithms

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11
Q

Explain organ allocation using kidneys as an example

A

Organ allocation – Kidney:

 5 tiers of patient – paediatric/adult, sensitised/not-sensitised

 7 elements:
 • Waiting time
 • HLA-matching + age
 • Donor-recipient age difference
 • Location
 • HLA-DR homozygosity
 • HLA-B homozygosity
 • ABO blood group matching
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12
Q

Difference in DBD vs. DCD kidney transplant?

A

DBD transplant
• patient assessed NATIONALLY

DCD transplant
• patient assessed LOCALLY

This is so the kidneys can be implanted with less warm ischaemia

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13
Q

Strategies to increase transplantation activity?

A
  1. Increased deceased donation
  2. Increased living donation
  3. Xenotransplantation & stem cell research opportunities
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14
Q

Half-life for kidney transplant?

A

10 YEARS

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15
Q

The I.S recognises someone else’s organ as foreign - what are the most important variations in clinical transplanation?

A

Most relevant PROTEIN variations in clinical transplantation:

(1) ABO blood group
(2) HLA coded on Chr6 by the MHC

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16
Q

Explain how the ABO blood groups poses an issue for transplation

A

A and B proteins are found on:
• RBCs & endothelial lining on blood vessels in the transplanted organ

 Circulating pre-formed anti-antibodies will bind to the donor endothelium and = antibody mediated rejection

17
Q

What makes up the ABO blood groups?

A

O+
• 1x fructose
• 1x n-acetyl-glucosamine
• 2x galactose

A+ 
 • 1x fructose
 • 1x n-acetyl-glucosamine
 • 2x galactose
 • 1x n-acetyl-galactosamine

B+
• 1x fructose
• 1x n-acetyl-glucosamine
• 3x galactose

18
Q

How can the ABO blood group issue be tackled?

A

ABO-imcompatible transplantation can occur but:

  • remove Abs in recipient blood
  • often = good outcomes for KIDNEY, HEART, LIVER
19
Q

Explain why HLA can cause an issue with transplantations

A

These are highly variable cell surface markers of self

 HLA types:
 o Class 1 – A, B, C 
  – expressed on ALL cells
 o Class 2 – DR, DQ, DP 
  – expressed by APCs

 HLA molecules are highly pleomorphic with lots of alleles for each to be encoded with
• individuals most often have 2 types of each HLA molecule due to 2 chromosomes (mum and dad)

20
Q

Explain what is meant by MM

A

Number of mismatches!
• compared between HLA-A, B & DR

o 0-6 is acceptable
– more miss-match equals more chance of death later down the road
o Sibling –> sibling transplant = 25% chance of 0MM 6MM 50% chance of 3MM

(Onenote!!)

21
Q

What can an I.R cause due to the highly pleomorphic MHC molecules

A

Exposure to foreign HLA can result in I.R to the FOREIGN EPITOPES

Can cause:
• Immune graft damage & failure i.e. rejection

Diagnosis - histological examination

Treatment - immunosuppresive drugs

22
Q

Define Rejection

A

Can be either
• T-cell mediated
OR
• Ab-mediated

It can also either be:
• hyperacute / acute / chronic

23
Q

Explain T-cell mediated rejection

A

Lymphocytes infiltrate the interstitial area
• they rupture the tubular BM = cause tublitis = local organ damage

The graft can be infiltrate by allo-reactive CD4+ cells
• CTLs can release granzyme B, perforin & FasL
• Macrophages can phagocytose, release proteases, produce cytokines & radicals

24
Q

Explain Ab-mediated rejection

A

Abs against:
• graft HLA & AB antigens

Abs arise:
• pre-transplantation (‘sensitised’) - patient already exposes in pregnancy or previous transplantation

• post-transplantation (‘de novo’)

May see features of BOTH forms of rejection in graft rejected patients

25
Q

How to monitor transplantation?

A

Watch for deteriorating graft function

E.g.
• Kidney, - reduced GFR, rise if creatinine, fluid retention

  • Liver - rise if LFTs, coagulopathy
  • Lungs - breathlessness, pulmonary infiltrate
26
Q

How to prevent rejection?

A
  1. Maximise HLA compatibility

2. Life-ling immunosuppressive drugs

27
Q

Treatment for rejection?

A

Immunosuppressive drugs!!

28
Q

How do immunosuppressive drugs work?

A

(1) Target T-cell activation and proliferation
• Anti-CD3 ABs, JAK3 inhibitors, Azathioprine, cyclosporine

(1) Target B-cell activation, proliferation and antibody production
• Splenectomy, anti-CD20 ABs, Bortezomib (proteasome inhibitor), anti-C5, intravenous immunoglobulin plasma exchange (IVIG).

29
Q

What is the standard immunosuppressive regime?

A

(1) Pre-transplantation
– Induction agent (T-cell depletion or cytokine blockade)

(2) From implantation
– base-line immunosuppression:
 Signal transduction blockade – CNI inhibitors – e.g. Cyclosporine.
 Anti-proliferative agents – Azathioprine
 Corticosteroids

(3) If needed
– treatment of acute rejection.
 T-cell mediated – steroids, anti-T agents.
 Antibody dependant – IVIG, plasma exchange, anti-CD20, anti-complement

30
Q

Post-transplant infections?

A

Post-transplant on Immunosuppressives gives you a higher chance of conventional infections

o Opportunistic infections
– cytomegalovirus, BK virus, Pneumocytis carinii, Murcormycosis, CMV

31
Q

What are the post-transplantation malignancy?

A

o Skin cancer
o Post-transplant lymphoproliferative disorder (EBV driven)
o Other i.e. Kaposi’s Sarcoma

Year 2 - MCD Immunology (6 decks)

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