Lecture #13

Question 1

Graft

Answer 1

Transplanted tissue/ organ

Question 2

Ortotopic transplantation

Answer 2

The graft is placed in its normal anatomical position

Question 3

Heterotrophic tranplantation

Answer 3

The graft is placed not in its normal anatomic position

Question 4

Isograft/ syngraft

Answer 4

The donor and the recipient are homozygotic tweens

Question 5

Autograft

Answer 5

The donor and the recipient are the same person

Question 6

Allograft

Answer 6

The donor and the recipient are different persons

Question 7

Xenograft

Answer 7

The donor is an animal

Question 8

Primary rejection of an allograft Ex skin allograft

Answer 8

10-14 days

The tissue establishes blood supply (angiogenesis) - immune cells are infiltrated - thrombosis - ischemia - necrosis

Question 9

Secondary rejection of an allograft Ex skin allograft

Answer 9

5-6 days
The tissue already has blood supply therefore infiltration of immune cells is rapid so does thrombus - ischemia and necrosis

Question 10

Critical matching criteria between donor and recipient

Answer 10

1. Major histocompetability complex
   mainly HLD-A HLA-B HLA-DR
2. Minor histocompetability molecules
   H-Y on the Y chromosome, HA1-HA5 autosomal peptideson HSC
3. ABO Rh blood groups, VEC vascular endothelial cells antigen system, SK Skjelbred antigen

Question 11

Liver transplantation survival rates

Answer 11

1y survival over 75%

5y survival 70%

Question 12

Heart transplantation

Answer 12

We preform heart transplant only if the patient has more then 50% to die in the present year
5y survival is 80% after 5y CHD will develope

Question 13

Pancreas transplantation

Answer 13

1y survival 72% but improves along with kidney transplantation

Question 14

Cornea transplantation

Answer 14

60-70% acceptance

HLA matching is not prerequisite

Question 15

Direct alloreactivity

Answer 15

1. Sensitization - the donor’s APCs will go to the lymph nodes and present their self antigen to T cells
2. Rejection - activated lymphocytes (all types) will reach the organ via blood circulation and attack it (humoral and cytotoxic)

ACUTE and intense

Question 16

Indirect alloreactivity

Answer 16

1. Sensitization - the recipient’s APCs will engolf antigns from the transplanted tissue and present them to T cells in the lymph nodes
2. Rejection - activated lymphocytes (mainly Th1 and B cells) will reach the organ via blood circulation and produce Ab against the antigens (humoral mainly)

CHRONIC and mild

Question 17

3 types of HVG reactions (in solid organs)

Answer 17

1. Hyperacute - Preformed Ab against antigens of the donor due to previous exposure to ABO, HLA, VEC antigens
   Ex: pregnancy, abortion, blood transfusion, previous organtransplantation
   The mechanism of rejection is humoral (vasculitis)
2. Acute - Can be humoral (vasculitis) or cellular (parenchymal damage)
3. Chronic - mediated by Th1 and macrophages - granuloma formation - fibrosis - loss of activitiy of the organ

Question 18

How do we prevent transplantation rejection?

Answer 18

1. Donor selection
2. In vitro graft manipulation - elimination of the donor’s immunocompetent cells by steroid infusion/ tolerance induction/ anti CD28/ anti CD4/ anti MHCII…
3. Immunosuppression of the recipient by anti IL2R, anti TCR, abatacept, GCS (inhibit cytokine production)

Question 19

What are the conditions to development of GVHR?

Answer 19

1. Presence of immunocompetent cells in the graft
   (bone marrow, thymus, spleen, neonatal blood transfusion but also liver, lung, gut)
2. Impaired imune defense of the recipient
3. Different HLA genes or minor histocompetability molecules

Question 20

In GVHR the damage to the recipient cells is via

Answer 20

Apoptosis

Fas-FasL , TNF, granzymes and perforins