Joint Lecture: Transplantation immunology & rejection

Question 1

What is the definition of transplantation?

Answer 1

Transplantation is the transfer of cells, tissues or organs from one part of the body to another or from one individual to another.

Question 2

What are the types of grafts?

Answer 2

Autograft
Isograft
Allograft
Xenografts

Question 3

What is each of the following?

autograft
Isograft
Allograft
Xenograft

Answer 3

autograft: Graft between 2 sites within the same individual.

Isograft: Graft between 2 genetically identical individuals.

Allograft: Graft between 2 genetically dissimilar animals of the same species.

xenograft: Graft between 2 animals of different species.

Question 4

what are the genes coding for histocompatibility Antigens divided into?

Answer 4

• MHC where incompatibility leads to rapid rejection.

- Minor transplantation antigens: incompatibility leads to slow rejection.

Question 5

What are the main complications of organ transplantation?

Answer 5

1) Problems with the preservation and reperfusion of the donor organ.
2) Technical/surgical complications.
3) Rejection.
4) Complications of immunosuppressive therapy.
5) Recurrence of the original disease for which transplantation was carried out

Question 6

What are the types of rejection?

Answer 6

1) Hyperacute graft rejection
2) Acute rejection
3) Chronic (long term) rejection

Question 7

When does hyperacute graft rejection take place?

Answer 7

Occurs few hours after transplantation.

Question 8

What is the cause of hyperacute graft rejection?

Answer 8

• It is due to preformed antibodies, either natural antibodies to blood type antigens or anti-MHC antibodies formed in response to blood transfusions or previous transplants, or developed during pregnancy to the baby’s paternal MHC antigens.

Question 9

What are the effectors of hyperacute graft rejection and what is the result?

Answer 9

• Antibodies react with antigens on vascular endothelial cells and activate complement inducing its pathway.
• The resulting damage blocks blood vessels and damages the transplanted organ.

Question 10

What is a Pathology of hyperacute rejection?

Answer 10

Grossly: The kidney rapidly becomes cyanotic, mottled, and flaccid.

Microscopically: Immunoglobulin and complement are deposited in the vessel wall, causing:
1- Endothelial injury and fibrin-platelet thrombi.
2- Neutrophils accumulate within arterioles, glomeruli,
andperitubular capillaries.
3- As these changes become diffuse and intense, the glomeruli undergo thrombotic occlusion of the capillaries, and fibrinoid necrosis occurs in arterial walls.

Question 11

Where do much of our understanding of the pathological aspects Solid organ transplantation come from?

Answer 11

Much of our understanding of the pathologic aspects of solid-organ transplantation is based on studies of renal allografts due to that the kidneys were the first transplanted solid organ and transplanted more than any other organ.

Question 12

When does acute rejection take place?

Answer 12

• Occurs in few days, weeks or month following transplantation.

Question 13

What are the characteristics of acute Rejection?

Answer 13

• Cellular or humoral immune mechanisms may predominate.

- Cellular is the most commonly seen.

Question 14

What causes acute rejection?

Answer 14

As grafts contain donor antigen presenting cells that travel to the draining lymph nodes of the recipient and activate recipient T cells.

Question 15

What are the effectors in acute rejection?

Answer 15

• primarily cytotoxic T lymphocytes.

- These cells migrate to all tissues including the graft causing tissue damage.

Question 16

What controls acute rejection?

Answer 16

has been significantly controlled by immunosuppressive therapy.

Question 17

What is a Pathology of Acute cellular rejection?

Answer 17

Microscopically, there may be

1- Extensive interstitial inflammatory cell infiltration and edema as well as mild interstitial hemorrhage.

2- Glomerular and peritubular capillaries contain large numbers of inflammatory cells that may also invade the tubules, causing focal tubular necrosis.

3- In addition to causing tubular damage, CD8+ T cells may injure vascular endothelial cells, causing a so-called endothelitis.

• The affected vessels have swollen endothelial cells.

Question 18

What is the Pathology of Acute humoral rejection (rejection vasculitis)?

Answer 18

This may take the form of:

1- Necrotizing vasculitis with endothelial cell necrosis, neutrophilic infiltration, complement, and fibrin, and thrombosis.

2- Such lesions are associated with extensive necrosis of the renal parenchyma.

Question 19

When does chronic rejection take place?

Answer 19

after months or years.

Question 20

What causes chronic rejection?

Answer 20

• Due to uptake of graft antigens by recipient APC.
• Then, peptides from both MHC and minor histocompatibility antigens are presented by recipient antigen presenting cells.

Question 21

What are the effectors in chronic rejection?

Answer 21

Th1 cells that activate macrophages to cause chronic inflammation that leads to tissue injury and scarring.

Question 22

What is the Pathology of chronic rejection?

Answer 22

Chronic rejection is dominated by:

1- Vascular changes, interstitial fibrosis, and tubular atrophy with loss of renal parenchyma.

 The vascular changes consist of dense, intimal fibrosis, principally in the cortical arteries.

2- These vascular lesions result in renal ischemia, manifested by glomerular loss, interstitial fibrosis and tubular atrophy, and shrinkage of the renal parenchyma.

3- The glomeruli may show scarring, with duplication of basement membranes; this appearance is sometimes called chronic transplant glomerulopathy.

4- Chronically rejecting kidneys usually have interstitial mononuclear cell infiltrates of plasma cells and numerous eosinophils.

Question 23

Where does graft versus host disease occur?

Answer 23

bone marrow transplantation

Question 24

What causes graft versus host disease?

Answer 24

 The host possesses histocompatibility antigens that the graft lacks (occur to both MHC and minor H antigens).

 The graft contains immunologically competent cells.

Question 25

What are the symptoms of GVHD?

Answer 25

include rashes, diarrhea, and pneumonitis.

Question 26

Mention the procedures done to enhance graft survival.

Answer 26

Donor selection
Recipient preparation
Immuno-suppression

Question 27

How are donors selected in graft transplantation?

Answer 27

 The most important in donor selection is the MHC identity with the recipient; an identical twin is the ideal donor.

 Grafts from an HLA-matched sibling have 95-100% chance of success.

 Organs from a two or one DR matched cadaver have been used also with some success.

 In every case, ABO compatibility is essential.

Question 28

How is the recipient prepared in transplantation?

Answer 28

• Immune suppression increases the risk of infection so protect the recipient by isolation and prophylactic antibiotics.

Question 29

how does immunosuppression take place in transplantation?

Answer 29

 Anti-inflammatory agents: Corticosteroids.

 Cytotoxic drugs:

• They block DNA synthesis and affect rapidly dividing cells.
• Azathioprine and cyclophosphamide are the most commonly used.

 Others: Cyclosporin A and tacrolimus