Chapter 16: Transplantation Immunology

Question 1

Major histocompatibility complex (MHC)

Answer 1

○ Closely linked genes on chromosome 6
○ Highly polymorphic and induce strong graft rejection

Question 2

Class I proteins

Answer 2

○ Includes HLA-A, HLA-B, HLA-C
○ Expressed on all nucleated cells

Question 3

Class II proteins

Answer 3

○ Includes HLA-D (DR, DQ, DP)
○ Expressed on antigen-presenting cells (APCs)

Question 4

HLA genes are linked and inherited in what way?

Answer 4

○ Mendelian fashion as haplotypes
○ One paternal (a or b) and one maternal (c or d) haplotype is passed to each offspring
○ Four different combinations of haplotypes are possible in offspring

Question 5

What are the possible ways for people to inherit HLA halotype?

Answer 5

○ 25% chance two siblings will inherit the same two haplotypes
○ 50% chance two siblings will be HLA haploidentical, share one of two HLA haplotypes
○ 25% chance two siblings being HLA nonidentical, share neither haplotype

Question 6

Classification of Grafts

Answer 6

○ Autograft
○ Syngeneic (Iso) graft
○ Allograft
○ Xenograft

Question 7

Autograft

Answer 7

○ Tissue transfer in the same individual
○ saphenous vein in cardiac bypass

Question 8

Syngeneic (Iso) graft

Answer 8

○ Transfer of cells or tissues to a genetically identical individual
○ transplant between identical twins

Question 9

Allograft

Answer 9

○ Graft between genetically nonidentical individuals of the same species
○ graft from an unrelated cadaver donor

Question 10

Xenograft

Answer 10

○ Transplant between members of different species
○ transplant of pig valve into human heart

Question 11

Direct Allorecognition

Answer 11

○ Cytotoxic T cells from the recipient bind directly to foreign HLA antigens on cells of the allograft and release cytotoxic factors

Question 12

Indirect Allorecognition

Answer 12

Host APCs present foreign MHC antigens on graft cells to recipient Th cells

Question 13

Types of Graft Rejection

Answer 13

○ Hyperacute
○ Accelerated
○ Acute
○ Chronic

Question 14

Hyperacute

Answer 14

Graft Rejection that occurs minutes to hours after the transplant

Question 15

Accelerated

Answer 15

Graft Rejection that occurs several days after the transplant

Question 16

Acute

Answer 16

Graft Rejection that occurs days to months after the transplant

Question 17

Chronic

Answer 17

Rejection 1 year or more after the transplant

Question 18

Graft-Versus-Host Disease (GVHD)

Answer 18

○ Lymphoid cells in graft mount immune response against recipient’s histocompatibility antigens
○ Caused by immune response of T cells in donor HSC, lung, or liver transplants

Question 19

Immunosuppressive Agents

Answer 19

○ Corticosteroids- Anti-inflammatory
○ Antimetabolites- Interfere with lymphocyte maturation and division
○ Calcineurin inhibitors- Block cytokine synthesis in T cells
○ Monoclonal antibodies- Interfere with T-cell or B-cell function by binding to lymphocyte surface molecules
○ Polyclonal antibodies- Animal-derived antibodies against human cells that deplete thymocytes or lymphocytes

Question 20

HLA Typing

Answer 20

Identification of HLA antigens or genes in transplant candidate or donor

Question 21

How is HLA typing done?

Answer 21

HLA antigens identified by their reactivity with panels of antisera

Question 22

HLA Genotyping

Answer 22

Identification of HLA alleles

Question 23

What is the advantage of HLA Genotyping over CDC?

Answer 23

○ Higher resolution
○ Reagent quality
○ High throughput

Question 24

HLA antibodies may develop in response to what?

Answer 24

○ multiple blood transfusions
○ prior organ transplants
○ paternally derived fetal antigens by pregnant women

Question 25

What can HLA antibodies lead to?

Answer 25

cause hyperacute graft rejection

Question 26

HLA typing by CDC method

Answer 26

○ Patient serum incubated with panels of lymphocytes
○ Anti-human Ig can increase test sensitivity
○ % panel reactive antibody (%PRA) reported