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Flashcards in Transplantation Deck (35)
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1

What situation leads to a transplant?

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

2

What are the 4 major types of graft?

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

3

Define Histocompatibility?

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

4

Where are HLA alleles found?

on chromosome 6

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

5

How are HLA alleles inherited

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

6

What are the major requirements for tissue typing?

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

And ABO blood group

7

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

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

8

What does HLA-DR code for?

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

9

What are privileged sites?

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

E.g. Cornea

10

What are the major causes of rejection?

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

11

How do we categorize rejection?

Immediate
Acute
Chronic

12

What causes an immediate rejection?

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

Happens in minutes

13

Acute rejection occurs within 6 months. What happens?

Cell & Ab mediated

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

14

What happens in chronic rejection?

Ab mediated & innate immunity

This is the most common kind

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

15

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

Corticosteroids
Anti-thymocyte Globulin
Plasmapharesis

16

how do you prevent someone rejecting an organ?

ABO matching
Tissue Typing (HLA)
Prophylactic Immunosuppresants

17

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

Infection
Neoplasia
Drug SEs
Recurrence of disease
Surgical complications

18

What are the types of immunosuppresants used in organ transplant?

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

19

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

In rejection the host attacks the graft

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

20

So what is required for GvH disease?

Graft must contain immunocompetent cells

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

HLA mismatch

21

What can we do to prevent GvH?

Tissue Typing (HLA)

Can do Donor Marrow T cell Depletion

22

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

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

23

What causes hyperacute rejection in unmodified xenografts?

Natural IgM Human Anti-Swine Abs

24

Define Autologous transplant

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

25

Synergeneic transplant definition

Transplant between identical twins (isograft)

26

Allogenic transplant definition

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

27

Cadaveric transplant definition

Uses organs from a dead donor

28

Xenogenic transplant

Transplant between species, thus carrying a high risk of rejection

29

How do we chose a recipient for an organ?

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

30

What happens in autologous SCT?

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