Transplantation

Question 1

Autograft

Answer 1

(One person) from one organ to another

Question 2

Isograft

Answer 2

(Genetically idential) From one person to another

Question 3

Allograft

Answer 3

(Genetically different) One person to another of same species

Question 4

Xenograft

Answer 4

(Genetically different) one species to another

Question 5

Major molecular factor in graft rejection

Answer 5

MHC/HLA 1 and 2 found on short arm of chr. 6

Question 6

Differences between MHC 1 and 2 on the molecular level

Answer 6

MHC 1 has A,B,C where the alpha chain is variable and the B chain is invariable.
MHC 2 has DP, DQ, DR where both alpha and B chains are variable.

Question 7

T/F MHC 1 is present on all nucleated cells while MHC 2 is on specific ones

Answer 7

T

Question 8

T/F HLA antigens are inherited in a Mendelian dominant manner

Answer 8

T

Question 9

Direct presentation of alloantigens to MHC. What kind of graft rejection does this result in?

Answer 9

Allogenic APC (the donor) shows its MHC to the recepients T cells. Cellular rejection (CD4, CD8)

Question 10

Indirect presentation of alloantigens to MHC. What kind of graft rejection does this result in?

Answer 10

Recepient APC recognises foreign peptides and alerts self T cells. Humoral rejection (B cells produce antibodies and T cells proliferate)

Question 11

Types of host v graft rejections

Answer 11

Hyperacute: (7 min) when you have pre-existing abs to donor tissue
Acute: (8-11 days) CD4 and CD8 mediated
Chronic (aka delayed type hypersensitivity): (3 months to 10 years) Both CD4 and ab mediated
Xenograft: (7 min) Pre-existing abs to donor tissue

Question 12

How does hyperacute rejection occur?

Answer 12

preformed ab are present in recepient (could be due to prev platelet transfusions or Haploidentical transplantation)
complement system activates:
- For solid organ transplants: inflammation, thrombosis formation, neutrophil margination
- For HSCT: innate immune cell activation and CD34 cells

Question 13

Immunosuppresives and how they decrease likelihood of GVHD

Answer 13

• interrupt lymphocyte division (cyclosporin, mycophenolate, tacrolimus)
• Deplete lymphocytes (antithymoglobulin, steroids)
• Interfere with lymphocyte maturation (cyclosporin, ruxolitinib)
• Interfere with immune cell co-stimulation (anti-ctla4, anti-CCR5)
• Facilitate induction of tolerance (sirolimus)
• Adoptive Tcell therapy (Treg)

Question 14

Indications for allo-HSCT

Answer 14

AML, MDS, NHL, ALL

Question 15

Factors affecting outcome of Allo-HSCT

Answer 15

conditioning
graft source
GVHD prophylaxis (mainly calcineurin inhibitors like cyclosporine and tacrolimus, along with additions like antimetabolites MTX/MCP. Post transplant cyclophosphamide is given)
Donor

Question 16

T/F ATG is more immunosuppressive that PT-Cy and is associated with higher chance of CMV and EBV reactivation

Answer 16

T

Question 17

Side effects of allogenic transplant

Answer 17

GVHD
endothelial complications: veno-occlusive disease, thrombotic microangiopathy
-cytokine release syndrome, macrophage activation syndrome
- infections

Question 18

RF for chronic GVHD

Answer 18

age >18
gvhd prophylaxis
previous acute GVHD

Question 19

RF for acute GVHD

Answer 19

HLA disparity
Donor was CMV+
Allo immunized donor
Intensity of conditioning

Question 20

GVHD treatments

Answer 20

first: steroids
second: ruxolitinib
third: chose any from ATG, ECP, MMF, fecal transplant, anti-TNF