Nelson- Transplant Rejection

Question 1

Define autograft

Answer 1

self to self

skin graft

Question 2

Define isograft

Answer 2

syngenic b/t 2 identical twins

Question 3

define allograft

Answer 3

Between genetically different individuals of the same species

Question 4

Define xenograft

Answer 4

between 2 species

porcine heart valve to human

Question 5

Using one word, state the major barrier to successful transplantation.

Answer 5

REJECTION

recipient’s IS recognizes the graft as being foreign and attacks it
cell mediated or Ab mediated

Question 6

State the two groups of antigens that are most important in determining the likelihood of transplant rejection.

Answer 6

ABO and HLA compatible grafts have better chance of avoiding rejection

ABO-endothelial cells
HLA- MHCI (all nucleated cells), MHC II (APCs)

*most impt are HLA-A, B, C, minor importance DR

Question 7

What is cellular rejection? How does it vary?

Answer 7

T cell mediated graft rejection

Destruction of donated graft cells by recipient CD8 T cells
Delayed hypersensitivity rxns triggered by activated recipient CD4 T helper lymphocytes

**Rejection depends on differences in highly pleomorphic HLA alleles

Question 8

What are the two pathways by which recepient’s T cells recognize the donor alloantigens?

Answer 8

Direct

Indirect

Question 9

Explain direct cellular rejection.

Answer 9

1. Donor MHC I and II antigens on APCs are recognized by host CD8 and CD4 T cells
2. CD4 T cells> proliferate> produce IFNy> local delayed hypersensitivity reaction
3. CD8T cells> CTLS> kill graft cells

Question 10

Explain indirect cellular rejection and how does it relate to humoral rejection.

Answer 10

1. Graft antigens are picked up and displayed by host APC.
2. CD4 T cells are activated> proliferate> produce IFNy> local delayed hypersensitivity
3. CD4 T cells stimulate B lymphocytes > produce Ab (humoral rejection

Question 11

What are the major types of pre-formed alloantibodies?

Answer 11

Abs to ABO blood group antigens (naturally occurring

Preformed anti-HLA Abs (pregnancy, previous transfusion, prevoius transplant)

Question 12

What type of rejection reaction is possible if preformed Abs are present?

Answer 12

Hyperactue rejection reaction

Question 13

What is the rationale for pre-transplant testing?

Answer 13

Key immonological factors affect graft survival:
ABO compatibility
close matching of HLA loci
absence of preformed anti-HLA Abs

Question 14

What does pretransplant testing include?

Answer 14

ABO compatibilty testing of donor and recipient
HLA typing of donor and recipient
detection of pre-formed anti-HLA ab in recipients serum
Lymphocyte cross match- react recipient serum against donor lymphocytes

Question 15

What is the difference in terms of timing of hyperacute, actue and chronic rejection?

Answer 15

hyperacute- begins suddnely w/ in minutes-hrs of transplant

acute- days to wks

chronic- months/yrs

Question 16

What is the immunological mechanism of hyperacute rejection? What type of sensitivity is this?

Answer 16

Incompatible ABO Ab or preformed anti HLA Ab bind endothelial Ag>
complement activation>
vessel thrombi and ischemic necrosis

Type II hypersensitivity

Question 17

What is the immunological mechanism of acute rejection? What type of sensitivity is this?

Answer 17

Cell mediated hypersensitivity- host CD4 T cells release cytokines, activating host macrophages and CD8 T cells

Ab mediated hypersensitivity rxns- host CD4 T cells release cytokines which promote B cells to differentiatie into plasma cells> produce anti-HLA Abs that bind endothelial Ag

Question 18

What is the immunological mechanism of chornic rejection? What type of sensitivity is this?

Answer 18

Often secondary to vascular injury

result of both cell-mediated and ab-mediated hypersensitivity rxns

Question 19

Which type of rejection is the most common cause of renal graft failure?

Answer 19

Chronic rejection

Question 20

What is seen pathologically w/ all three rejections? W/ which one is the deposition of C4d seen?

Answer 20

Hyperacute: vascular thrombosis> acute fibrinoid necrosis

Acute cell mediated: inflammatory cells in interstitium and b/t endothelial cells

Actue humoral: inflammatory cells and proliferating smooth muscle cells in blood vessel> vasculitis> thrombosis> fibrosis/narrowing> ischemic injury *C4d

Chronic: graft atherosclerosis (vascular lumen repleaced by cells)

Question 21

What are the major complications associated w/ immunosuppresssive therapy in the transplant setting?

Answer 21

1. Increased susceptibility to opportunistic infections/ common community required disease
2. Increased risk of malignancies (EBV, SCC, KS)

Question 22

What is a hematopoietic cell transplant? What is it used to treat? What are the two types?

Answer 22

Administration of hematopoietic cells from source to reconstitute BM

Malignancies, aplastic anemias, thalassemias, some immunodeficiencies

Autologous
allogenic

Question 23

What is an autologous HCT?

Answer 23

HPC derived from individual w/ disorder

Question 24

What is an allogenic HCT?

Answer 24

HPCs from someone else

Question 25

What is GVHD?

Answer 25

Immunologically competent donor T cells recognize the recipients HLA antigens as foreign and react against them

Host is unable to mount IR against grafted lymphocytes
Allows graft lymphocytes to attack host

Question 26

What is used to prevent GVHD and when is their no risk of GVHD?

Answer 26

HLA typing for allogenic HCT donor

Autologous HCT

Question 27

What causes acute GVHD?

Answer 27

Occurs cytokines > cell injury

Question 28

What organs are involved w/ acute GVHD?

Answer 28

skin- severe dermatitis
liver- destruction of bile ducts> jaundice
GI tract- mucosal ulceration > bloody diarrhea

Question 29

What organs are involved in chronic GVHD?

Answer 29

> 100 days following allogenic HCT

skin-loss of appendages w/ dermal fibrosis
liver- chronic liver disease > cholestatic jaundice
GI tract- fibrous structures, malabsorption, chronic diarrhea
lungs- obliterative bronchiolitis