Transplant Rejection

Question 1

Define autograft and give an example

Answer 1

self to self donation - like a skin graft

Question 2

definte isograft

Answer 2

syngeneic between identical twins

Question 3

define allograft

Answer 3

a transplant between genetically different individuals of the same species

Question 4

define xenograft

Answer 4

a transplant between two species - like a pig heart valve to humans

Question 5

What’s the major barrier to successful transplantation?

Answer 5

rejection

Question 6

Is rejection a cell-mediated or antibody-mediated issue?

Answer 6

both can be involved

Question 7

What two groups of antigens are most important in determining the likelihood of transplant rejection?

Answer 7

ABO antigens and MHC (HLA typing)

Question 8

What are the four HLA loci that are most involved in transplant rejection?

Answer 8

HLA-A, HLA-B, HLA-C, HLA-DR

Question 9

Describe the process of direct cellular rejection.

Answer 9

DONOR nor class 1 and 2 MHC antigens on APCs in the graft are recognized by host CD8+ cytotoxic T cells and CD4 T cells.

The CD4 cells produce cytokines which induce tissue damage by a delayed hypersensitivity reaction

the CD8 cells kill the graft cells

(so donor antigen is presented by donor APCs to host cells)

Question 10

Describe the process of indirect cellular rejection

Answer 10

Graft antigens are picked up, processed and displayed on HOST APCs to activate CD4 T cells, which damage the graft by local delayed HSR and stimulate B lymphocytes to produce antibodies

(so donor antigen is presented by host APCs to host cells)

Question 11

What are the major types of pre-formed alloantibodies

Answer 11

antibodies to ABO blood group antigens (naturally occurring)

pre-formed anti-HLA antibodies (after pregnancy, previous transfusion or previous transplant)

Question 12

What type of rejection reaction occurs if there are preformed antibodies present?

Answer 12

hyperacute rejection reaction

Question 13

Antibody-dependent acute humoral rejection is usually manifested in what?

Answer 13

afftects the vasculature and results in rejection vasculitis

Question 14

What does pretransplant testing include?

Answer 14

1. ABO compatability of donor and recipient
2. HLA typing of donor and recipient
3. Detection of pre-formed anti-HLA antibodies in recipient’s serum
4. Performance of a lymphocyte cross-match (recipients serum with donor lymphocytes)

Question 15

What are the three types of rejection?

Answer 15

hyperacute, acute and chronic

Question 16

What happens in hyperacute rejection?

Answer 16

immediately type II antibody-mediated hypersensitivity reaction with preformed anti-HLA antibodies or ABO incompatibility

you get vessel thrombi and ischemic necrosis within minutes to hours

(almost never happens - clerical error)

Question 17

What happens in acute rejection?

Answer 17

It’s a cell-mediated hypersensitivity reaction with host CD4 cells releasing cytokines, activation host macrophages and CD8 cells or from antibody-mediated hypersensitivity reactions

Occurs over days to weeks

Question 18

What happens in chronic rejection?

Answer 18

it’s both cell-mediated and antibody-mediated HSRs that occurs over months and years

Question 19

What is the most common type of rejection in the US and why?

Answer 19

chronic - because immunosuppression mainly controls acute rejection

Question 20

What are the two major complications of immunosuppressive therapy in the transplant setting?

Answer 20

increased susceptibility for opportunistic infections (and community acquired infections diseases too)

Increased risk of malignancies (squamous cell carcinoma of skin, kaposi sarcoma, etc.)

Question 21

What is an autologous hematopoietic cell transplantation?

Answer 21

you use hemaotpoietic progenitor cells derived from the individual with the disorder - you use their own cells

Question 22

What is an allogeneic hematopoietic cell transplantation?

Answer 22

you use the projenitor cells from someone else

Question 23

What’s the main risk in doing an allogeneic hematopoietic cell transplantaiton?

Answer 23

graft vs host disease: the immunocompetent T cells from the DONOR may recognize host cells as foriegn and attack the new host

Question 24

How can GVHD be avoided?

Answer 24

Do appropriate HLA typing and irradiate the blood before transfusion

Question 25

Describe what happens in acute GVHD? WHat organs are usually affected?

Answer 25

Arbitrarily occurs in the first 100 days

direct cytotoxicity by CD8 cells as well as injury from cytokines released by CD4 cells - typically skin, liver and GI tract epithelium most affected

Question 26

Describe what happens in chronic GVHD? What organs are usually affected?

Answer 26

Arbitrarily occurs after the first 100 days - either a continuation of acute or a new onset

you get dermal fibrosis, chronic liver disease with jaundice and fibrous structures in the GI tract - malabsorption and chronic diarrhea. lungs may show obliterative bronchiolitis

Question 27

Why is immunodeficiency a complication of hematopoietic cell transplantaiton?

Answer 27

1. can occur because of the prior treatment
2. prior myeloablative therapy in prep for the fragt
3. delay in repopulation of the recipient’s immune system