Immunology 2: Transplantation Flashcards
When do you transplant organs? 2 categories? how many a year?
When they organs have failed
either life saving-liver heart, small bowel
Life enhancing-kidneys (less dyalisis)
Pancreas-in selecte case better than insulin injection
QOL-cornea, reconstructive surgery
5000 a year-kidneys, pancrease, heart, liver, intestine-but manage 50000
Why do organs fail?
tons-and each organs have specific diseases and reasons-
liver-infection, drugs, alcohol
Kidneys-diabetic and other
What is an allograft? Autograft? Iso? Xeno? what is the main used one
allo-same species
auto-same person-if could grow organs
iso-same genetic make up
xeno-different specie-heart vavles from cow/pig, skin
mainly use allografts-solid organs, cells (BM, pancreas), temporary-blood, cornea, framwork (bone), composite-face, hand. Uterus
What are the 2 sources of organ?
Decreased donor-2 types-after brain death (DBD) and after circulatoiry death (CBD) (usually seen as less efficient)
Living donor-bone marrow, kidney, liver –better match if related
be sure to establish neurological death
What are things that must be true for an organ to be donated in deceased donor?
be sure of death-neurological
exclude-viral inferction, malignancy, drug abuse, disease
once done-organ removed and rapidely cooled (done by NHS blood and transplant
What is the difference between transplant selection and allocation?
selection-done by local team-decide if you have what it takes
allocation-how they are given once they become available
-> need to be fair and efficient-waiting for long, hard to match, best match?, surival efficiency
patient seprated in tiers-peads or adult, sensitised or not
main elements: Waiting time, HLA mathc, donor recipient age difference
gap has been going better-but stil 6000 people waiting
How have organ transplant acitivity been increased?
Deceased donation-more marginal cases taken
living- transplant across tissue compatibility, exchnage programs
future-xeno? Stem cell?
What are the 2 main reason for immune system rejects of organs?
HLA and ABO groups
What is the ABO groups and why does it matter in transplantation? whats the solution?
carbohydrate chains on RBC but also on endothelial cels
naturally occuring against anti A/B (opposite of what you have-AB-has none, O has both
group-A-has A chain, B-B chain, AB-both, O-none
endothelial chains are the one that are bad in transplant-inflammation of vessels
modern solution-remove the AB’s with plasma exchange-works veyr well
what are HLA molecules?
Human leukocyte antigens, or MHC
vary a lot between people
important in defence infection and neoplasia (presenting antigen to adaptive immune system)
Remember MHC and stuff
transplanted cells have their own HLA (1 or 2)-and they are seen as foreign AG by APC-uptaken and shown to Tcells like bacterial Ag on their own HLA
What are the different forms of HLA types?
Class I-A,B,C -1 a chain, 1 b microglobulin
Class II-Dr, DQ, DP-1a and 1b (symetrical)
each are very polymorphic
A, B , DR are usually the ones seen in transplant issues
How are mistatches calculated and notes?
well have 2 alleles in each HLA molecule-
compares A-can have 2 mismatches-noted as 0/1/2
Compare B-same
DR-again
potentially 6 mismathc there
MM: 1,2,0 (if 1 miss on A, 2 on B and 0 DR)
Other HLA are becoming more important as discoveries happen
siblings match better but not alawys perfect
What are the types of organ rejection?
Can be classified either by what the reaction is (T cell, antibody, mixed) or when it happens (hyperacute, acute, chronic)
More common are acute and chronic because careful on transplant
what are the features of T cell rejection?
Ag from donor shedded and taken by host APC-activate T cells-> home to the foreign Ag (teher, roll, arrest, diapesis)–then attack everything
interitial infiltraion, rupture or tubular BM, tubulitis
also recruit CD8 T cells, macrophages, etc-with cytokines-amplify
on biopsy-dark cells (immune) in the interstitium-usually T cells-tubulitis
what are the features of AB mediated rejection?
AB against ABO or HLA (rarely to other things)
either pre transplant (like Anti ABO), or post transplantation-de novo
pre-transplant are worse-faster bigger response
AB bind donor HLA antigen-activate complement, increase immune cell adhesion/recruitment to area-increase inflammation => necrosis and innlam
see immune cells in tubules-but mainly INTRAVASCULAR-unlike t cell medaited-can also see complement activation
