Lecture 21 /22 - Transplantaiton Immunology Flashcards
Define the terms autograft, isograft, allograft, and xenografts.
L21 S5
Autograft:
-graft from one part of an individual to another part of the same individual
Isograft:
-graft from one individual to another genetically identical individual (between twins)
Allograft:
-graft from one individual to another, non-genetically identical individual
Xenograft:
-graft between members of different species
What HLA classes are important to consider for transplantation?
L28 S7
Class I HLA:
- HLA-A
- HLA-B
Class II HLA:
- HLA-DP
- HLA-DQ
- HLA-DR
Differentiate between direct and indirect allorecognition.
L21 S11-12
Direct:
-MHC of donor cells recognized by and activates recipient T cells
Indirect:
- Ag of donor is processed by recipient APCs and recognized by recipient T cells
- important in chronic rejection
What are the types of rejection and what is the timing of the reaction?
L21 S13
Hyperacute:
- occurs in minutes to hours
- caused by preformed antidonor Abs and complement
Accelerated:
- occurs in days
- reactivating of sensitized T cells
Acute:
- occurs in weeks to day
- primary activation of T cells
Chronic:
- occurs in weeks to years
- results form immunologic and non-immunologic factors
What is the process of hyperacute graft rejection?
L21 S14
Caused by pre-existing Abs in the blood that are reactive to donor Ags
Examples:
- ABO incompatibility
- sensitization to donor MHC (due to repeated previous transplants/transfusions or pregnancy)
Results in complement activation and death of donor endothelium
What is the process of acute graft rejection?
L21 S15
Caused by primary activation of T cells (CD4+ or CD8+)
Direct or indirect pathway
Donor DCs can move to lymph nodes where they initiate a primary immune response
or
Recipient CD8+ cells can recognize class I MHC of donor cells
What is the process of chronic graft rejection?
L21 S16
Recipient immune system believes donor MHC is a self MHC carrying Ag. Results in occlusion of blood vessels and ischemia of donor organ.
Indirect pathway
Can also be caused by Ab mediated deposition of complement in donor organ
What non-immunologic factors must be considered for an transplant?
L21 S21
Mechanical trauma to graft tissue and ischemia-repercussion injury.
When transplanted, damaged grafts release clotting factors such as fibrin and fibrinopeptides which serve as chemoattractants to Mφ and neutrophils.
Also bradykinin is released increasing vascular permeability and vasodilation.
These events can lead to rejection.
What workup must be done prior to transplantation?
L21 S22
- determining ABO compatibility
- identification of class I HLAs
- crossmatching to test for preformed Abs against donor HLA
- identification of class II HLA
What transplantation are ABO matching not important for?
L21 S23
- cornea
- heart valve
- bone/tendon graft
How is class I HLA typing achieved?
L21 S31
Certain individual are immunized against HLA Ags to produce anti-HLA Ab.
Anti-HLA Ab are introduced to sample containing lymphocytes.
If Ab binds Ag, classical complement pathway will be activated and lymphocyte will be lysed which is detected with staining methods.
How is cross matching achieved and what is the purpose?
L21 S35
Tests for preformed Abs against donor HLA
Recipient serum is introduced to donor cells to test for preformed Abs against donor cells (microcytotoxicity test).
If Abs are present cell damage will occur (via complement MAC) and is indicated by dye absorption by cell.
How is class II HLA typing achieved?
L21 S39
Lymphocytes of donor are irradiated to prevent proliferation to produce stimulator cells.
Stimulator cells present donor MHC Ags to recipient lymphocytes (responder cells).
Responder cells will be activated and proliferate when exposed to stimulator class II MHC that are not the same.
What are the characteristics of host versus graft and what are its effector mechanisms?
L21 S43-44
Stronger than response against pathogens (significantly more T cells are responsive to allogenic APCs than pathogens)
Has immune memory; second graft will be rejected more rapidly
Mechanisms:
- humoral via Th2 (IL-4, 5, and 10)
- cellular via Th1 (Il-2 and IFN-γ)
What are the characteristics of graft versus host and what are its effector mechanisms?
L21 S46
Occurs in transplants of small bowel, lung, or liver (due to native donor T cells)
Occurs in immunocomprimised recipients (due to inability to reject allogenic cells)
Mechanism:
-stimulation of recipient cell apoptosis by donor CTL
