Chapter 16: Transplantation Immunology Flashcards
Major histocompatibility complex (MHC)
○ Closely linked genes on chromosome 6
○ Highly polymorphic and induce strong graft rejection
Class I proteins
○ Includes HLA-A, HLA-B, HLA-C
○ Expressed on all nucleated cells
Class II proteins
○ Includes HLA-D (DR, DQ, DP)
○ Expressed on antigen-presenting cells (APCs)
HLA genes are linked and inherited in what way?
○ 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
What are the possible ways for people to inherit HLA halotype?
○ 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
Classification of Grafts
○ Autograft
○ Syngeneic (Iso) graft
○ Allograft
○ Xenograft
Autograft
○ Tissue transfer in the same individual
○ saphenous vein in cardiac bypass
Syngeneic (Iso) graft
○ Transfer of cells or tissues to a genetically identical individual
○ transplant between identical twins
Allograft
○ Graft between genetically nonidentical individuals of the same species
○ graft from an unrelated cadaver donor
Xenograft
○ Transplant between members of different species
○ transplant of pig valve into human heart
Direct Allorecognition
○ Cytotoxic T cells from the recipient bind directly to foreign HLA antigens on cells of the allograft and release cytotoxic factors
Indirect Allorecognition
Host APCs present foreign MHC antigens on graft cells to recipient Th cells
Types of Graft Rejection
○ Hyperacute
○ Accelerated
○ Acute
○ Chronic
Hyperacute
Graft Rejection that occurs minutes to hours after the transplant
Accelerated
Graft Rejection that occurs several days after the transplant
Acute
Graft Rejection that occurs days to months after the transplant
Chronic
Rejection 1 year or more after the transplant
Graft-Versus-Host Disease (GVHD)
○ 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
Immunosuppressive Agents
○ 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
HLA Typing
Identification of HLA antigens or genes in transplant candidate or donor
How is HLA typing done?
HLA antigens identified by their reactivity with panels of antisera
HLA Genotyping
Identification of HLA alleles
What is the advantage of HLA Genotyping over CDC?
○ Higher resolution
○ Reagent quality
○ High throughput
HLA antibodies may develop in response to what?
○ multiple blood transfusions
○ prior organ transplants
○ paternally derived fetal antigens by pregnant women
What can HLA antibodies lead to?
cause hyperacute graft rejection
HLA typing by CDC method
○ Patient serum incubated with panels of lymphocytes
○ Anti-human Ig can increase test sensitivity
○ % panel reactive antibody (%PRA) reported
