FMS Week 10: Transplantation Flashcards
Transplantation Definition
Transplantation is the process of taking cells, tissues, or organs, called a graft, from one individual (donor) and placing them into an individual (Recipient)
Autograft Definition
from one part of the body to another e.g. trunk to arm
Isograft Definition
between genetically identical individuals (e.g. monozygotic twins, or within an inbred strain)
Allograft Definition
between different members of the same species (e.g. Mr. Smith to Mr. Jones)
Xenograft Definition
between members of different species (e.g. monkey to man)
HLA Mismatches AKA
Alloantigens
HLA Mismatches can lead to …
Transplant Rejection
Types of transplant rejection
2 listed
- Transplant Rejection
- Host-versus-Graft Disease
HLA Class I is expressed on what cells
HLA Class I is expressed on all nucleated cells
HLA Class II is expressed on which cells?
HLA Class II is expressed on Professional Antigen Presenting Cells (APCs) such as
- Dendritic Cells (DCs)
- Macrophages (Monocytes)
HLA Class II is upregulated on?
Endothelial cells
Type of HLA expression
Co-dominant expression
Co-dominant expression definition
Maternal and Paternal alleles are fully expressed
MHC alleles are on which chromosome?
Chromosome 6
MHC Class II Haplotypes
3 listed
- HLA-DP
- HLA-DQ
- HLA-DRB1
MHC Class I Haplotypes
3 Listed
- HLA-B
- HLA-C
- HLA-A
Main ways to be exposed to HLA proteins
3 listed
- Transfusion
- Pregnancy
- Transplant
3 Pathways of allorecognition
- Direct
- Semi-Direct
- Indirect
Direct Allorecognition Mechanism
Recipient T cell recognizes self or non-self peptide represented on non-self MHC from a donor APC
Semidirect Allorecognition Mechanism
2 listed
- Recipient T cell recognizes non-self peptides on self MHC on Recipient APC
- Recipient T Cell Recognizes self peptide on non-self MHC on Recipient APC
Indirect Allorecognition Mechanism
Recipient T cell recognizes non-self peptide on self MHC on recipient APC
Direct Allorecognition accounts for what % of Allorecognition?
1-10%
Indirect Allorecognition accounts for what % of Allorecognition?
< 0.1 %
Semidirect Allorecognition accounts for what % of Allorecognition?
~90%
Direct Allorecognition Donor or Recipient APC?
Donor APC
Semidirect Allorecognition Donor or Recipient APC?
Recipient APC
Indirect Allorecognition Donor or Recipient APC?
Recipient APC
Mixed Lymphocyte Reaction Steps
4 listed
- Mix blood mononuclear cells from two donors in tissue culture
- Responder T cell recognition of allogeneic MHC Class I & II molecules
- Clonal expansion and functional differentiation of responder T cells
- Effector functions of both CD8 and CD4 T cells
Mixed Lymphocyte Reaction: MHC Class I Interactions and Result
4 Listed
- Recipient CD8 T Lymphocyte (Responder cell) recognizes MHC Class I presented on allogeneic Donor APC
- Recipient allogeneic CD8 CTLs are activated
- Allogeneic CTLs kill and lyse target cell expressing allogeneic MHC
Mixed Lymphocyte Reaction: MHC Class II Interactions and Result
4 Listed
- Recipient CD4 T Lymphocyte (Responder cell) recognizes MHC Class II presented on allogeneic Donor APC
- Recipient allogeneic CD4 Helper T cells are activated
- Allogeneic Helper T Cells secrete cytokines when contacting Allogeneic Donor MHC Class II
Immunological Components of Rejection
SEE LATER
Types of Rejection Reactions of Solid Organ Transplants
4 Listed
- Hyperacute
- Accelerated
- Acute
- Chronic
Hyperacute rejection timeline
minutes-hours
Hyperacute Rejection Cause
Preexisting anti-donor antibodies in the recipient and complement
Accelerated Rejection Timeline
Days
Accelerated Rejection Cause
Reactivation of sensitized lymphocytes against donor antigens (memory response)
Acute Rejection Timeline
Days-weeks/months
Acute Rejection Cause
Primary activation of lymphocytes against donor antigens (de novo)
Chronic Rejection Timeline
months-years
Chronic Rejection Causes
5 listed
- HMI
- CMI
- Cytokines
- Immune Complexes
- Fibrosis
HMI AKA
Humoral Immunity
CMI AKA
Cell-Mediated Immunity