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

Corticosteroids
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

Corticosteroids
Cyclosporinfor solid organ graft transplantation (by interferring with T cell signalling)
Calcineurin inhibitors (Tacrolimus) - inhibits IL-2 gene transcription
RIpamycin - interacts with signalling downstream of the IL-2 receptor
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

Question 24

Define Autologous transplant

Answer 24

Tissue returning to same individual after period outside the body, usually frozen, stem cells, skin graft, ovaries etc

Question 25

Synergeneic transplant definition

Answer 25

Transplant between identical twins (isograft)

Question 26

Allogenic transplant definition

Answer 26

transplant between genetically nonidentical members of the same species providing a risk of rejection

Question 27

Cadaveric transplant definition

Answer 27

Uses organs from a dead donor

Question 28

Xenogenic transplant

Answer 28

Transplant between species, thus carrying a high risk of rejection

Question 29

How do we chose a recipient for an organ?

Answer 29

ABO compatibility
Negative serum cross match with Donor’s T-lymphocytes
HLA match

Question 30

What happens in autologous SCT?

Answer 30

Marrow is removed, frozen and reinfused after potent chemotherapy has been given

Question 31

What is wrong with allogenic SCT?

Answer 31

MUCH RISKIER

Mortality is as high as 20%

Question 32

When is allogenic SCT carried out?

Answer 32

SCID

Aplastic aneamia

Question 33

Stem cells sources

Answer 33

Bone marrow
Peripheral blood
Cord blood

Question 34

How do we condition the patient before stem cell therapy?

Answer 34

High dose Chemo
High dose radio
To destroy diseased/damaged stem cells already present

Question 35

What is GVHD and when does it occur?

Answer 35

Graft versus Host disease occurs when donor T cells from allogenic graft react to recipient antigens due to a mismatch in either minor or major histocompatibility antigens.
Can occur up to 4 weeks later
Multisystemic
Acute = 70% mortality
Minimise T cells in donation