Transplantation

Question 1

Is HLA matching important for solid organ transplants?

Answer 1

Before cyclosporine and other immune suppressive drugs it was but now it’s not considered necessary for many types of organ transplants.

However, MHC matching is still important for HSCT.

Question 2

What is an alloantigen?

Answer 2

genetically determined to be in some individuals of a species

Question 3

When recipient T cells directly see alloantigens on donor APC

Answer 3

Direct recognition

Responsible for acute graft rejection

Question 4

When donor alloantigens are taken up and processed by recipient APC and presented to recipient T cells

Answer 4

Indirect recognition

Responsible for later stages of allograft rejection

Question 5

Autologous

Answer 5

Self

Question 6

Allogeneic

Answer 6

Another individual of the same species

Question 7

Xenogeneic

Answer 7

Different species

Question 8

Chimerism

Answer 8

Mixture of donor and recipient cells

Question 9

Hyperacute rejection

Answer 9

Major barrier to xenotransplantation, occurs within minutes

Complement activation, endothelial damage, inflammation and thrombosis

Question 10

Acute rejection

Answer 10

Can be cellular or humoral in nature; typically occurs within days to weeks in non-immune suppressed individuals or months-years in immune suppressed.
Parenchymal cell damage, interstitial inflammation

Question 11

Chronic rejection

Answer 11

Major cause of graft failure (b/c of improvements in treatment for acute)
Occurs within months to years, vascular changes, interstitial fibrosis, loss of renal parenchyma; get renal ischemia due to loss of glomeruli, interstitial fibrosis and tubular atrophy.
Chronic inflammatory reaction in vessel wall, intimal smooth muscle cell proliferation, vessel occlusion.

Question 12

Name some drugs that help prevent graft rejection.

Answer 12

Cyclosporine
Mycophenolate mofetil 
Rapamycin 
Corticosteroids
Anti-IL-2 receptor antibody

Question 13

What must a patient undergo before HSCT?

Answer 13

Chemotherapy and/or irradiation to eliminate malignant cells and make space for incoming cells

Question 14

What are minor histocompatibility antigens (miHA)?

Answer 14

Less potent at inducing graft rejection; Cleaved and processed endogenous proteins that occupy the binding groove of MHC class-1 and class-2 molecules
Contain genetic polymorphism– usually due to SNPs. Can be either MHC class-1 or class-2 restricted.

Question 15

What is the mixed lymphocyte reaction?

Answer 15

A way in culture to measure alloreactivity and mimics what happens in vivo

Question 16

Explain acute GVHD.

Answer 16

Results from reactivity of donor T cells against histocompatibility antigens of the recipient. In acute GVHD, mature T cells in donor graft recognize and react against host antigens, creating a potentially fatal immune response.

Question 17

Explain chronic GVHD.

Answer 17

Late complication (>100d) with autoimmune-like features; thought to be from cytokine and T cell dysregulation.

Question 18

Explain graft vs tumor effect.

Answer 18

Graft contains donor T lymphocytes that are beneficial for recipient because they eliminate residual host T cells or tumors. Develops after recognizing tumor-specific or recipient-specific alloantigens.

Question 19

What is the main difference between direct and indirect alloantigen recognition??

Answer 19

The source of the APC.
Direct the APC is donor.
Indirect the APC Is recipient.