Transplant Immunology B6 Flashcards
HS 1 antibody or cell mediated? what antibody?
antibody IgE
HS 2 and HS 3 antibody or cell mediated? what antibody?
antibody IgG and IgM
HS 4 antibody or cell mediated? what antibody?
cell mediated, T cell driven
Act of transferring cells tissues or organs (GRAFT) from one individual (DONOR) to another (Recipient)
Transplant
Self tissue transferred from one body site to another in the same individual
Autografts
Tissue transferred between genetically identical individuals
Isograft
Tissue transferred between genetically different members of the same species.
Allograft
Tissue transferred between different species
Xenograft
Host vs Graft disease
Transplanted tissue is rejected by host
Graft vs host disease
Immunocompromised (IMPORTANT)
-Host is attacked by tranplanted T-cells
Every nucleated cell has ____.
HLA is on short arm of Chromosome 6
Not all HLA are equal in HLA rejection…. what are the 3?
HLA-A, HLA-B and
HLA-DR=MOST IMPORTANT
HLA-A HLA-B are what MHC?
MHC I
HLA-DR is what MHC?
MHC II
_____________ are second most common transplanted tissue in US is what? what is number 1?
Cornea transplants (32,000 per year) Blood is #1 (5,000,000 per year)
Cornea does not express _________.
HLA/MHC
What happens in a graft acceptance AutoGraft?
Chunk of tissue dropped into skin
Wait 7 days, vessels have reconnected and healing
2 weeks= total resolution, vascularization, lymphocytes and white blood cells don’t recognize anything foreign… Neutrophils come in and clean it up
______ are critical in transplant rejection.
T-cells
What happens in graft rejection?
Day 3-7 REvascularization
Day 7-10 Cellular infiltration
Day 10-14 Thrombosis and necrosis
Damaged vascularization and reject necrotic tissue
Why are we worried on first graft?
If rejected on first graft, likely to not accept on second graft.
_________ play central role in rejection, but cLassical cause of rejection is ________
Thymus (T-cells)
Lymphocytes
Rats devoid of thymus accept _________
xenografts
Long survival of _______ in children with thymic deficiency
allografts
______ and _____ cells are involved in graft rejection.
CD4 and CD8
If you block CD8 alone what happens?
If you block CD4 alone what happens?
If you block CD8 and CD4 what happens?
Graft rejected in ~15 days (Same as control, might think CD8 doesn’t play role, but… hold on)
Graft rejected in ~30 days (CD4 plays key role)
Graft rejected in ~60 days (CD4 and CD8 are playing a role.
When we are looking at tranplanting an organ we want to make sure what?
Make sure ABO compatible, (blood types compatible)
Dont want to transplant tissues that are ABO incompatible.
These play a role in graft rejection:
Antibody-mediated cytotoxicity
Cell-mediate / Delayed type hypersensitivity
Type II hypersensitivity
Type IV
Every immune reaction starts with _________.
sensitization
Cell that recognizes MHC- II?
CD4 Traffic cop
Cell that recognizes MHC I?
CD8
During sensitization what happens?
donor and recipient APCs migrate from graft to stimulate activation of T lymphocytes
In effector stage what happens?
Antibody mediated component, Type II antibody dependent cytotoxicity
-complement activation and cell lysis
Cytokines released by Th cells play central role in what?
IL 2, IFN gamma, TNF beta
IL-2 does what?
promotes T cell proliferation (CTLs)
TNF alpha and TNF beta are ________ to tissues and play role in inflammatory response
cytotoxic
IFN gamma promotes _________ response, promotes influx of macrophages. Upregulates MHC I and II to make sure they are real (IMPORTANT)
Delayed type hypersensitivity (HS TYPE 4)
Hyper acute reaction is an _____________ rejection. (IMPORTANT)
antibody-mediated (TYPE 2 HS)
TNF B ________ foreign cells. (IMPORTANT)
Lyses
An acute rejection is an __________ rejection. (IMPORTANT)
Cell-mediated (Type IV)
T-cell driven
There are antibodies to MHC/HLA if they are preexisting they can have a __________ response.
Hyper acute
(min to hours to days)
Pre existing antibodies to HLA
-This can happen because of previous blood transfusions (WBCs)
Chronic rejection is a ___________ and _________ rejection. (IMPORTANT)
Antibody (TYPE 2 HS) and cell mediated (TYPE IV HS)
Renal graft failure takes weeks up to 6 months…
Acute
Renal graft failure takes >6 months
Chronic
Mononuclear cells
CD4 cells
Acute rejection happens within ______.
weeks
Chronic develops _____ or ______ after transplantation.
months or years
How do we test tissue typing?
Test for HLA through Microcytotoxicity test
IF you have a blue circle the cell had what?
Cell had MHC antigen on it. Find the matched donor. Do they match ABO type?
Which match is more important in survival of graft?
MHC-II
HLA A and B are most important in which MHC class?
MHC-I
HLA DR is most important in what MHC class?
MHC-II
Compatibility is determined by mixing killed donor lymphocytes (MHC) with recipient lymphocytes. See if they activate when come into contact.
Mixed Lymph Response
In MLR a low number means what and a high number means what?
Low number= patient is happy
High number= patient is not happy
Whats the requirement for a cornea transplant?
nothing, no MHC