lecture 32 - transplantation

Question 1

What kinds of grafts can take place

Answer 1

Autograft: within self
Isograft: syngenic, twin → twin
allograft : human → human
Xenograft: transgenic, human → other species

Question 2

What role doe sMHC/ play in graft rejection?

Answer 2

Grafts tolerated with same haplotype
Rejection with different haplotype
Due to T cell mediated responses → IFN-gamma
Memory can be induced

Question 3

Describe the most common mechanism of graft rejection

Answer 3

Allorecognition in graft recognition

Recipient T cells recognize incompatible HLA antigens by the donor APC

Question 4

What is MHC testing?

Answer 4

Identifies donor recipient painting with lowest risk of complications
PCR
MLR for class II mismatching, mixed lymphocyte reaction
Mix MHC cells and irradiated MHC non T cells as antigen presenting cells → measure T cell proliferation by incorporation of 3H-thymidine → proliferation depends on differences in class II alleles
Take s2-3 days
Bad sign if T cells expand
Minor histocompatibility antigens
Even if MHC is identical, rejection can be caused by minor H antigen mediated
Ie slower rejection from male to female due to HY antigen coded on the Y chromosome

Question 5

What is the role of T cells in rejection

Answer 5

T cells recognize foreign HLA
Inactivation reduces graft rejection → immunosuppression results
Helper CD4 T cells produce cytokines which stimulate CD8, inflammation ndf antibody production
Rapoamycin blocks lymphocyte proliferation
Corticosteroids antiinflammatory and suppress immune function

Question 6

Describe the role of antibodies in rejection

Answer 6

Hyper-acure rejection if recipient has preformed antibodies against donor antigens
Immune complex formation
Formation of membrane attack complex by complement cascade
Ab bidn to vascular endothelium in graft → active complement → inflammation and obstruction of blood vessels → graft engorged and dies

Question 7

Summarize the pattern of allograft rejection

Answer 7

Hyperacute: within 24 hours, preformed antibodies
Acute: 10 days to a few weeks, humoral and cell mediated immunity
Chronic: several months to years,minor H antigen humoural and cell mediated

Question 8

What is graft vs host reaction

Answer 8

Donor’s immune cells completely replace those of the recipient, with bone marrow transplants
Donor’s T cells deplete T cells with depletion antibodies that bind CD3
Strong response can be fatal