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Immunology > 3. Transplantation > Flashcards

3. Transplantation Flashcards

1
Q

When is a ‘life enhancing’ transplantation done?

A

Occur in organs where other-life support methods aren’t as good e.g. dialysis

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2
Q 
Why do the following organs fail:
• Cornea
• Skin
• Bone marrow
• Kidney
• Liver
• Heart
• Lungs
• Pancreas
• Small bowel
A
  • Cornea - degenerative disease, infection, trauma
  • Skin - burn, trauma, tumour
  • Bone marrow - tumour, hereditary disease
  • Kidney - diabetes, HT, glomerulonephritis
  • Liver - cirrhosis
  • Heart - CAD, cardiomyopathy, congenital defects
  • Lungs - COPD, CF, pulmonary HT
  • Pancreas - T1DM
  • Small bowel - hereditary conditions or related to prematurity
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3
Q

What is an autograft?

A

Transplantation within the same individual

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4
Q

What is an isograft?

A

Transplantation between genetically identical individuals of the same species

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5
Q

What is an allograft?

A

Transplantation between different individuals of the same species

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6
Q

What is an xenograft?

A

Transplantation between different species (e.g. heart valves and surgical skin plasters)

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7
Q

What is a prosthetic graft?

A

Using plastic or metal

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8
Q

Give examples of future autograft surgery

A
  • Using stem cells to make full organs
  • At the moment they can be transferred into various cell lineages - hard to organise them into 3D structures
  • Can use scaffolds to form 3D structures
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9
Q 
Give examples of the following types of allografts:
• Free cells
• Temporary
• Privileged sites
• Framework
• Composite
A
  • Free cells - bone marrow, pancreas islets
  • Temporary - blood
  • Privileged sites - cornea
  • Framework - cartilage, nerves
  • Composite - hands, face, larynx
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10
Q

What is a composite graft?

A

A graft involving several tissues e.g. face transplant involve skeletal muscle, skin and blood vessels

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11
Q

What is an orthotopic and heterotopic transplant?

A
  • Orthotopic - organ placed where it should be e.g. liver

* Heterotopic - organs placed elsewhere in the body e.g. kidneys and pancreas

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12
Q

Where are transplanted kidneys often placed?

A
  • In the iliac fossa

* Attached to the iliac vessels

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13
Q

What is the pancreas plumbed onto and transplanted with?

A
  • Plumbed onto the iliac arteries

* Transplanted with a segment of bowel

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14
Q

What type of organ can be transplanted from a living donor?

A
  • Bone marrow
  • Kidney
  • Liver
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15
Q

Describe the 2 main types of deceased donation

A
  • DBD (donor after brain death) - need to confirm brain death, mainly road accident and cerebral haemorrhage, harvest organs and cool
  • DCD (donor after cardiac death) - suitable for kidney transplant, long period of warm ischaemia time can cause damage
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16
Q

What potentially reversible things can cause apnoeic coma?

A
  • Depressant drugs
  • Metabolic or endocrine disturbance
  • Hypothermia
  • Neuromuscular blockers
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17
Q

How can a lack of brain stem function be demonstrated?

A
  • Pupils both fixed to light
  • Corneal reflex absent
  • No eye movements with cold caloric test
  • No cranial nerve motor responses
  • No gag reflex
  • No respiratory movements on disconnection (with PaCO2 > 50 mmHg)
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18
Q

What has to be excluded before using a DBD/DCD patient before transplantation?

A
  • Viral infection e.g. HIV, HBV
  • Malignancy
  • Drug abuse
  • Overdose
  • Poison
  • Disease of the organ to be transplanted
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19
Q

What is the absolute maximum and ideal cold ischaemia time for the kidney?

A

60 hours (ideally <24h)

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20
Q

What does transplant selection and allocation refer to?

A
  • Selection - access to waiting list

* Allocation - access to organ

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21
Q

What are the contraindications to being placed on the transplant selection list?

A
  • Too early - still has some organ function
  • Co-morbidity - medical, psychiatric, surgical e.g. CV disease, malignancy, compliance
  • Patient does not want a transplant
22
Q

What is considered in transplant allocation?

A

Equity
• What is fair?
• Time on waiting list
• Urgent? imminent death

Efficiency
• What is the best use for the organ in terms of survival

23
Q

What does it mean by kidney transplants being highly sensitised?

A

Likely to develop rejection if they receive a transplant

24
Q

How many tiers are there in kidney allocation and what do they depend on?

A
  • 5 tiers

* Depends on age and sensitivity

25
Q

What are the 7 elements for receiving a donation?

A
  • Waiting time
  • HLA match and age combined
  • Donor-recipient age difference
  • Location of patient, relative to donor
  • HLA-DR homozygosity
  • HLA-B homozygosity
  • Blood group match
26
Q

What is the main obstacle to donation?

A

Familial consent

27
Q

What is a donor transplant coordinator?

A
  • Registered nurse with experience in critical care
  • Employment to shift from transplant centres to NHS BT (blood + transplant)
  • Potential donors a+e/ICU
  • Carry out family interviews - part of bereavement servicea
28
Q

What is the half life of a kidney from a deceased and living donor?

A
  • Deceased - 10 years

* Living - 13/14 years

29
Q

Does a transplant kidney last forever (lifetime)?

A

No, down to the immunology of transplantation

30
Q

HLA coded on which chromosome by HLA is relevant (in transplantation)?

A

Chr6

31
Q

Where are A and B carbohydrates found apart from red blood cells?

A

Endothelial lining of blood vessels in transplanted organs

32
Q

What happens if you transplant an organ from a donor that has a different blood type?

A
  • Recipients antibodies bind to the antigen on the endothelial cells of the donor organ
  • Activation of complement and thrombosis
  • Immediate, acute rejection
33
Q

How can we remove antibodies to prevent acute rejection by ABO-incompatible transplant?

A

Plasma exchange

34
Q

What does the recipient’s APC present in the context of a transplant and what cells does this activate?

A
  • APC presents donor’s HLA peptide

* T cell activation for T cells that are allo-specific

35
Q

What are the 6 different types of HLA?

A
  • Class I - A, B, C

* Class II - DP, DQ, DR

36
Q

Where are Class I and II HLA expressed?

A
  • Class I - all cells

* Class II - DR, DQ, DP - APCs but also upregulated on other cells

37
Q

How polymorphic is HLA?

A
  • Highly

* Lots of alleles for each locus

38
Q

How many types for each HLA molecule does each individual most often have?

A
  • 2 types for each HLA

* One maternal and one paternal

39
Q

Briefly describe the structure of HLA class I and II?

A
  • Class I - contains α (1, 2, 3) chain and β-microglobulin – the peptide binding grove is only comprised of α
  • Class II - contains α (1, 2) and β (1, 2) chain - peptide binding groove comprises both α and β
40
Q

Are all HLA antigens immunogenic?

A

No

41
Q

What range of HLA mismatches can you have with a potential donor?

A

0 to 6

42
Q

Describe T cell mediated rejection

A

• APCs take up fragments from the donated organ antigen
• Circulate to the lymph nodes and present antigen
• T cells that can mount an allo-specific response come into contact
- initially through CD4+
• CD4+ infiltrates the organ
• Recruit inflammatory cells - organ damage e.g. CD8+ and macrophages

(occurs in tubules and interstitium)

43
Q

Describe antibody-mediated rejection

A

• There are antibodies against graft HLA and AB antigen
• Antibodies can arise:
- pre-transplantation (sensitised) e.g. blood transfusions, previous grafts, pregnancy
- post-transplantation (de novo) i.e. most patients
• Endothelium is the main target

(intravascular process)

44
Q

What can be used for detecting a deteriorating graft function in:
• Kidney transplant
• Liver transplant
• Lung transplant

A
  • Kidney transplant - rise in creatinine, fluid retention, HT
  • Liver transplant - rise in LFTs, coagulopathy
  • Lung transplant - breathlessness, pulmonary infiltrate
45
Q

How can a heart transplant be monitored for rejection?

A

Regular biopsies

46
Q

What do immunosuppressive drugs target, with reference to transplant rejection?

A

• T cell and B cell activation and proliferation
- initial interaction between APC and T cell
- TCR interaction and co-stimulatory mechanisms
- nucleotide synthesis
• Cytokine production
• Antibody production

47
Q

What antibodies can be used before the organ is implanted to reduce the risk of rejection?

A
  • Anti-CD52 antibodies
  • Causes CD52 depletion
  • Kills off a lot of T-cells
  • Rituximab (anti-CD20)
  • Depletes B cells
  • Blocks the effect of complement
  • Bortezomib
  • Kills off plasma cells producing antibodies
48
Q

What immunosuppressants are used from time of implantation?

A
  • Signal transduction blockade - CNI inhibitor
  • Sometimes mTOR inhibitor
  • Antiproliferative agent
  • Corticosteroids
49
Q

What immunosuppressants can be used in episodes of acute rejection?

A
  • T-cell mediated: steroids, anti-T cell agents

* Antibody-mediated: IVIG, plasma exchange, anti-CD20, anti-complement

50
Q

Outline the changed risk of infection post-transplant?

A
  • Increased risk for conventional infections
  • Opportunistic infection - normally harmless e.g. CMV
  • Vulnerable to skin cancers
  • Post-transplant lymphoproliferative disorder - EBV driven
  • Other e.g. Kaposi’s sarcoma

Immunology (5 decks)

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