transplantation and tolerance

Question 1

role of MHC/HLA proteins in transplant tolerance

Answer 1

• MHC proteins encoded by HLA genes (MHC I = HLA-A, B, C and MHC II = HLA-D)
• codominant = proteins encoded by genes from both parents are expressed; inherit haplotype from each parent
• highly polymorphic and alloantigenic (different between members of the same species)
• matching HLA proteins (6/6 or 10/10) minimizes immune response to transplant
• still possibility for immune response from minor antigens => immune suppression required for all non-syngeneic transplants

Question 2

hyperacute rejection

Answer 2

• antibody (and complement) mediated
• occurs in minutes
• preformed anti-ABO anitbodies in host bind to ABO antigens in graft endothelium => complement activation (type II HR)
• almost always avoidable

Question 3

acute rejection

Answer 3

• CD8+ mediated (with CD4 and antibodies)
• occurs in weeks
• donor MHC recognized as non-self via direct or indirect pathways => direct killing of donor cells and development of antibodies
• direct non-self MHC recognition: host T cell TCR binds donor MHC and recognizes it as foreign => attack
• indirect non-self MHC recognition: phagocytosis of donor cells by APC’s and presentation of donor MHC peptide in contect of self MHC

Question 4

mixed lymphocyte reaction

Answer 4

• measures recognition of donor MHC by host T cells

- if host recognizes donor MHC => T cell activation and proliferation (CD4+ drive CD8+)

Question 5

chronic rejection

Answer 5

• CD4+/macrophage mediated (with antibodies and CD8)
• occurs in months/years
• APC’s present donor peptides => CD4+ T cells develop immune response against host (type IV HR) and donor specific antibodies can develop (type II HR)
• chronic inflammation => tissue damage and fibrosis

Question 6

GVHD

Answer 6

• immunocompetent donor T cells expand in recipient, recognize minor antigens, and destroy “non-self” recipient cells
• severe organ dysfunction, rash, diarrhea, jaundice
• most caused by stem cell and liver transplants
• can be beneficial in killing leukemia/lymphma!

Question 7

purpose and methods of immunosuppression

Answer 7

• reduce T cells

- drugs and antibodies (corticosteroids, anti-proliferative drugs, calcineurin inhibitors, mTOR inhibitor, antibodies)

Question 8

risks of immunosuppression

Answer 8

• increased susceptibility to infection and cancer

- common infections: legionella, nocardia, salmonella, CMV, fungi, parasites, mycobacteria