Transplant immunology

Question 1

what is HLA and where is it found

Answer 1

Human Leukocyte Antigen

• same as MHC
• key to self-discrimination

Question 2

where are 2 classes found

Answer 2

1 - most somatic cells

2 - B-cell, APCs

Question 3

where do we get our HLA from

Answer 3

one haplotype from each parent (co-dominant)

Question 4

how many important HLA are there

Answer 4

8 loci x 2 alleles = 16 alleles - there are many others too

Question 5

what does a 0/16 mismatch mean

Answer 5

close, but not perfect since others exist

Question 6

what is importance of mismatch

Answer 6

predict survival
0 - very good
less difference between 1and2and3 etc

Question 7

what is presently more important than HLA mismatch

Answer 7

presence of HLA antibodies to that HLA

Question 8

3 ways one might have anti-HLA ABs

Answer 8

1. preg.
2. blood transfusion
3. organ transplant

Question 9

what is crossmatch test

Answer 9

assessment of HLA ABs in serum before transplant

Question 10

what is complement dep. cytotoxitiy (CDC) crossmatch test

Answer 10

1. give recipient serum with AB
2. Ab binds HLA
3. antibody fixes complement
4. MAC formed and get holes
5. give dye and dye enters in
   - This is POSTIVE test (bad)

Question 11

what happens in tranplant with pos. CDC test

Answer 11

hyperacute rejection - immediate loss from anitbody that is there

Question 12

what is flow cytometry crossmatch test

Answer 12

more sens and spec.

1. donor cell and recipient serum
2. give fluresent tagged antiHLA AB AB (meta)
3. coulter counter

Question 13

what is most sensitive test

Answer 13

detection of HLA AB with beads coated with specific HLA antigens
- then use same method

Question 14

what happens if CDC neg, but other tests positive

Answer 14

acute antibody mediated rejection

• 7 days post- transplant
• activates memory cells

Question 15

what is importance of crossmatch test

Answer 15

1. pos. CDC is ABSOLUTE contrainidcaiotn

2. may still reject even if neg.

Question 16

what is panel reactive antibody (PRA) test

Answer 16

uses bead method to test a wide variety of different HLA

Question 17

what is result of PRA test

Answer 17

get virtual match which gives percent of match to all HLA within that type

Question 18

what is evidence between PRA and crossmatching

Answer 18

contrary reults

Question 19

what can happen in transplant even with no DSA

Answer 19

donor MHC presented to recipient T-cells - first step in activation

Question 20

3 signal model of Tcell activation

Answer 20

1. antigen specific TCR and MHC on APC
2. co-stim of CD28 on TC and CD80 on APC
3. T cell releases IL-2, which bind to CD25 and get mTOR and cell proliferation

Question 21

result of 3 signal model

Answer 21

produce many effector T-cells that eventually activate B-cells with graft AB

Question 22

what happen in acute rejection

Answer 22

activate T-cells enter graft

2. release cytokines - inflamm
3. direct killing of cells epxressing forreign HLA

Question 23

what do immunosuprresive drugs do (2)

Answer 23

1. block various pathways in the T-cell activation

2. Tcell depletion

Question 24

what are effects of T-cell depletion

Answer 24

1. prevents acute rej.
2. increase infection risk
3. increased malignancy
4. no prevention of humoral rejection

Question 25

what is antibody mediated (humoral) rejection

Answer 25

AB s bind HLA

- activates complement to kill

Question 26

what happens if knock out T and B cells

Answer 26

can still get rejection from monocytes

Question 27

what is tolerance

Answer 27

durable state of antigen-specific unresponsiveness, induced by exposure to antigen in a patient who is otherwise immuno-competent

Question 28

what is mixed chimerism

Answer 28

mixed population of donor and recipient T and B cells, so the donor supresses the host cells