Rejection

Question 1

Hyperacute rejection

Answer 1

mins to hours
Because of humeral response- pre-formed Ab
causes thrombosis and prevents revasc of graft

Question 2

Acute rejection

Answer 2

Days to weeks
Cell and humeral mediated
CD8 kill donor cells directly because of their MHC1
CD4 cells release CK
plasma cells make Ab against the donor cell vessel wall

Question 3

Chronic rejection

Answer 3

Cell and humeral
narrowing of graft vessels due to intimal wall proliferation

lungs- bronchiolitis obliterans
liver-vanishing bile duct
kidney- chronic allograft nephropathy
heart- accelerated atherosclerosis

Question 4

WHERE ARE MHC?

Answer 4

short arm chromosome 6

Question 5

When does HLA Dr have the most impact? HLA B? HLA A>

Answer 5

DR- first 6 months
B- 24 months
A- over 2 years

Question 6

If cold ischaemia time over 36 hours….

Answer 6

No effect/benefit HLA matching

Question 7

HLA DP, DR, DQ polymorphic or not?

Answer 7

DP and DQ are alpha and beta polymorphic

DR dimers have invariant alpha but beta is polymorphic

Question 8

Treat Ab mediated rejection

Answer 8

Plasma exchange
IVIg
Anti-C20 - depletes B cells but not memory cells
Proteosome inhibitors- Bortezomib

Question 9

Tac compared with cyclosporine

Answer 9

More diabetes
Less gum hypertrophy
Less hirsutism
Less hypertension and hyperlipidaemia

Question 10

best way to detect HLA Ab?

Answer 10

The luminex method

Question 11

What complement marker is a mediator of Ab mediated rejection?

Answer 11

Cd4

Question 12

What role do the dendritic cells transplanted play?

Answer 12

These stimulate “alloreactive” host T cells which are 10%!!! of host T cells breaking the rules of MHC restriction by responding to non self MHC plus peptide.

Question 13

Briefly describe direct and indirect pathways of allorecognition in renal

Answer 13

Direct

• allorecognition
• donor MCH1 stim host CD8–>direct kill
• donor MHC2 stim host CD4–>Th1 and Th17 responses

Indirect

• Donor DC replaced by host DC over weeks to months- normal presentation to CD4 cells (not CD8)
• then Ab formation and Th1 and 17 response

Note in GVHD - the host dendritic cells soon after transplant provide the direct effect and transplanted donor cells provide the indirect effect later on.

Question 14

Why has acute rejection decreased over the years?

Answer 14

CycA

Question 15

What immuno drugs are not that myelosupressive?

Answer 15

Tac and CycA

Question 16

Glucocorticoids work how?

Answer 16

Inhibit AP-1 and NFkB binding to DNA

also destabilises mRNA for CK production

Question 17

What is Basiliximab?

Answer 17

CD25 monclonal= the alpha chain of the IL-2 receptor
Expressed by activated T cells but not resting

given at induction at renal transplant
but the downside is that CD 25 is also a marker of T reg cells