CSIM 1.30 - Transplantation

Question 1

How are naive T-cells activated?

Answer 1

Binding to specific Ag presented by APC alongside a conjugate MHC molecule and co-stimulatory signals

Question 2

Where are MHC-class 1 molecules expressed?

Answer 2

T-cells
B-cells
Dendritic cells
Macrophages
Thymic corticle epithelial cells
ALL nucleated cells

Question 3

Where are MHC-class 2 molecules expressed?

Answer 3

Activate T-cells
B-cells
Macrophages
Thymic corticle epithelial cells

Question 4

Name the two MHC molecules properties?

Answer 4

Polygenic - several different MHC class 1/2 genes exist
Polymorphic - multiple variants of each gene (HLA-A1 - A303)

Question 5

Name the different polygenic forms of MHC-class 1?

Answer 5

HLA-A
HLA-B
HLA-C
Each person inherits one of each from either parent (x6)

Question 6

Name the different polygenic forms of MHC-class 2?

Answer 6

HLA-DR
HLA-DQ
HLA-DP
Each person inherits one of each from either parent (x6)

Question 7

In terms of the MHC polymorphic properties describe how MHC-restriction occurs?

Answer 7

A T-cell receptor activated by Influenza Ag in association with HLA-A1 will NOT recognise the same Ag in association with HLA-A2

Question 8

Describe direct allorecognition?

Answer 8

DONOR APC (from transplanted organ) migrates to recipient lymph node where recipient’s naive T-cells recognise the specific Ag and donor MHC molecule and secondary signal obtained (T-cell activation) - migrates to graft and rejects it

Question 9

What type of rejection is initiated by direct allorecognition?

Answer 9

Acute rejection via direct CD8 T-cytotoxic response

Question 10

Describe In-direct allorecognition?

Answer 10

RECIPIENT APC processes the Ag from the graft and presents this to recipient naive T-cell (recognition of specific Ag + self MHC + co-stimulatory signals) - T-cell activation - migrates to graft and rejects

Question 11

What type of rejection is initiated by In-direct allorecognition?

Answer 11

Chronic rejection as fewer T-cells are activated

Question 12

Describe hyperacute rejection and give an example?

Answer 12

Rejection within minutes
Recipient carries pre-existing antibodies against the Ag
ABO mismatch

Question 13

Describe acute rejection?

Answer 13

Graft accepted on average 13 days
T-cell mediated rejection occurs via CD8 T-cytotoxic cells/macrophages/NK-cells
Second graft from same donor = rejected more rapidly as alloreactive T-cells are now pre-formed

Question 14

Describe chronic rejection?

Answer 14

Concentration arteriosclerosis accumulating over a number of months/years
Infiltrative fibrosis is associated with ischaemia re-perfusion injury of transplant and alloreactive T-cells secrete CCL5 attracting more macrophages - Increased inflammation

Question 15

Describe graft vs Host disease?

Answer 15

Transplant bone marrow (new immune system) perceives the host as ‘foreign’ and attacks

Question 16

What criteria is used to diagnose graft vs Host disease?

Answer 16

Billingham criteria

Question 17

Describe the three phases involved in graft vs Host disease pathology?

Answer 17

Phase 1 - Tissue damage leads to inflammatory cytokine release
Phase 2 - Donor T-cell activation by up-regulated APC
Phase 3 - Expanded CD8 T-cytotoxic cell and NK-cell attack host tissues

Question 18

What is special about a corneal transplant?

Answer 18

Cornea is immune privileged (via BBB) therefore rarely rejected

Question 19

What is critical for a successful solid organ transplant and under what circumstances might this not be needed?

Answer 19

Blood group matching

Not required in infants

Question 20

What is critical for a successful bone-marrow transplant?

Answer 20

HLA matching