Transplantation

Question 1

What situation leads to a transplant?

Answer 1

“Tissue/organ undergone an Irreversible Pathological Process which either Threatens Patient’s Life or Significantly Hampers QoL

Question 2

What are the 4 major types of graft?

Answer 2

Xenograft - From an animal
Allograft - From another person
Isograft - From someone genetically identical
Autograft - From yourself

Question 3

Define Histocompatibility?

Answer 3

State in which the donor and recipient share the same (or sufficiently similar) alleles of HLA genes that they express the same MHC proteins and so would not attack the graft

Question 4

Where are HLA alleles found?

Answer 4

on chromosome 6

Each person has 2 sets of alleles and they are co-dominantly expressed

Question 5

How are HLA alleles inherited

Answer 5

As Haplotypes (meaning 2 half sets, one from each parent)

Hence each person is 1/2 identical to each parent and so has a 1/4 chance of being identical to a sibling

Question 6

What are the major requirements for tissue typing?

Answer 6

HLA match, particularly:
- HLA-A
- HLA-B
- HLA-DR

And ABO blood group

Question 7

What do HLA-A & HLA-B code for?

Answer 7

MHC 1
Found on all nucleated cells, present intracellular antigens and recognised by CD8+ T cells

Question 8

What does HLA-DR code for?

Answer 8

MHC 2
Found on APCs, presents extracellular antigens and recognised by CD4+ T cells

Question 9

What are privileged sites?

Answer 9

Places with little to no blood flow and so no immunity. They don’t require tissue matching or immunosuppression

E.g. Cornea

Question 10

What are the major causes of rejection?

Answer 10

HLA/ABO incompatible
Pre-formed immunity (sensitized to donor antigen)
Failed Immunosuppression (incl non-compliance)
Infections or environmental triggers

Question 11

How do we categorize rejection?

Answer 11

Immediate
Acute
Chronic

Question 12

What causes an immediate rejection?

Answer 12

HLA/ABO antibodies
They activate complement leading to inflammation and thrombosis

Happens in minutes

Question 13

Acute rejection occurs within 6 months. What happens?

Answer 13

Cell & Ab mediated

The graft is infiltrated by cells (T, B, NK & macrophages ) –> Endothelial damage and parenchymal cell damage

Question 14

What happens in chronic rejection?

Answer 14

Ab mediated & innate immunity

This is the most common kind

Chronic inflammation in blood vessels- -> smooth muscle proliferation –> Vessel occlusion and eventually organ failure

Question 15

How can you treat someone who’s rejecting their organ?

Answer 15

CCS
Anti-thymocyte Globulin
Plasmapharesis

Question 16

how do you prevent someone rejecting an organ?

Answer 16

ABO matching
Tissue Typing (HLA)
Prophylactic Immunosuppresants

Question 17

Other than rejection what else can go wrong in a transplant?

Answer 17

Infection
Neoplasia
Drug SEs
Recurrence of disease
Surgical complications

Question 18

What are the types of immunosuppresants used in organ transplant?

Answer 18

CCS
Calcineurin inhibitors (Tacrolimus) - inhibits IL-2 gene transcription
Anti-proliferatives (Azathioprine) - inhibit lymphocyte proliferation

Question 19

What’s the difference between graft rejection and Graftvshost disease?

Answer 19

In rejection the host attacks the graft

In GvH, white cells in the donated tissue attack the host’s body

Question 20

So what is required for GvH disease?

Answer 20

Graft must contain immunocompetent cells

Recipient must have defective immunity (pretty likely since you’re smacking them with immunosuppresants)

HLA mismatch

Question 21

What can we do to prevent GvH?

Answer 21

Tissue Typing (HLA)

Can do Donor Marrow T cell Depletion

Question 22

What kind of donors are associated with the longest life, least rejection and best health?

Answer 22

1) Living Donors (Related or unrelated)
2) Living donors altruistic
3) Brain Death Donors (DBD)
4) Cadaveric Death Donors (DCD)

So 4 are the least healthy transplants and 1 the most

Question 23

What causes hyperacute rejection in unmodified xenografts?

Answer 23

Natural IgM Human Anti-Swine Abs