Ch 16 Transplantation

Front 1

Transfusion

Back 1

transplantation of blood or plasma. B/c RBC have no nuclei, mostly have to just match type

Front 2

Allogeneic

Back 2

Transplantation from dif genetics w/in same species

Front 3

Syngeneic

Back 3

Same genetics- only identical twins

Front 4

Autologous

Back 4

Transplant where donor and recipient are the same person

Front 5

Xenogeneic

Back 5

Diff species

Front 6

What is initiating the transplant rejection?
What carries it out?

Back 6

Initiator: B or T cells, Ab

Action: MQ, NK, CTL, Ab

Front 7

First Set Rejection

Vs

Second Set Rejection

Back 7

First Set: 7-10 days- no memory cells

Second Set: 3 days- memory cells

Front 8

Direct Allo Rejection

Type?
Initiated by?

rejection?

Back 8

Host v Graft
No processing

Initiated by: Donor's DC

Donor DC has MHC and self-peptide that mimic the recipient --> can mobilize the recipient T cell

2 spots a piece: 2 MHC, 2 peptide

The peptide can mimic self or foreign...recipient T cells will start to attack the graft

Front 9

Allorecognition

Back 9

Recipient binding peptides of allogeneic graft.

Front 10

Why does a transplantation elicit a larger immune response than an infection?

Back 10

B/c all T cells will respond to the mimicked MHC, unlike specific T cells that are activated to specific infection

There are more autoreactive T cells and there are more MHC/peptide on the transplant surface
Based on number of:
MHC-specific DC
Matching receptors (on DC)

Front 11

Host v Graft

Back 11

Host rejecting Graft

Front 12

Indirect AlloRejection

type?
initiated by?

rejection?

Back 12

Host v Graft
Processed

Initiated by: Recipient APC

the APC phagocytoses it and processes and presents to host T cells

If it is a DC, can cross-present w/ MHC I and II.

Front 13

Mixed Lymphocyte Rxn

Tests for?
Stimulator?
Responder?

Back 13

Tests for Direct Allo Recognition ONLY

Responder: Recipient
Stimulator: Donor

Fix the recipient cells and add the donor's. If there is proliferation there is direct allorecognition.

CTL activated --> apoptosed cells
TH activated --> cytokine prod, T proliferation

Front 14

Hyperacute Rejection

Rxn time?
Type Ab?
How?
More likely in?

Back 14

Pre-existing Ab; Alloreactive Ab (host).

Rxn time: hours b/c Pre-existing Ab!

Mostly IgG and some IgM (circulatory)

Clogs vessels by host Ab attaching donor's antigens and forming complexes --> thrombosis (neutrophils, clotting)

Also initiates the classical complement cascade (IgG)

More likely in patients that have received previous transplant/transfusion

Front 15

Blood Typing

Universal receiver
Universal donor

Rh+/-

most restrictive
least restrictive

Back 15

Have to worry mostly about the Ab in the recipient, not donor

Universal Reciever: AB (no anti-Ab)
Universal Donor: O (no Ag)

Rh - is worse than + b/c can only receive blood from another person that does not have Rh factor.

Rh+ can receive from either

as recipient:
Most restricted: O-
Least restricted: AB+

Front 16

Acute Rejection

Rxn time?
Initiated by?
Pathology?

Back 16

7-10 days --> adaptive

Initiated by: TH1

Stimulates secretion of NEW Ab

Similar pathology, but not restricted to just vessels --> Parenchymal b/c TH1 can extravasate

Front 17

Chronic Rejection

Rxn Time?
Initiated by?
Pathology?

Back 17

Rxn Time: asymptomatic for a long time

MQ --> T --> MQ

starts as small rejection that activates the MQ

Cause Arteriolar Sclerosis: reduced lumen from clotting, scar tissue or SM growing into vessel

Scar tissue caused from MQ secreting FGF- and angiogenic factor and forming a fibrosis (unnecessary collagen growth)

Front 18

Cyclosporine

Back 18

Aimed at autorx T cells by inhibiting

calcenurin --> No IL-2 txt

but will inhib all T cells, not just allorx

Front 19

Azathioprine

Back 19

Blocks the IL-2 receptor (CD25)

Front 20

Mycophenolate Mofetil

Back 20

Stops B and T cell DNA synthesis

--> no proliferation

Front 21

Corticosteroids

Back 21

suppresses immune response via IL-1and TNF

used to stop chronic rejection

Front 22

CTLA-4-lg

Back 22

fusion of CTLA-4 and Fc of IgG

Fusion increases the half-life of CTLA-4

Remem: competes w/ CD28 for CD80/86 w/ higher affinity so that T cells cannot receive message to proliferate

Front 23

Anti-CD40L

Back 23

Binds to CD40L

Remem: only activated T cells

will block message or destroy T cell via complement cascade b/c it is made of IgG

Front 24

Anti-CD3 Monoclonal Ab

Back 24

Why? will anergize T cells

Front 25

Anti-CD25 (IL-2 receptor)

Back 25

Binds to CD25

Remem: only on new activated T cell and Tregs

Front 26

Photophoresis

purpose
when
steps

Back 26

-phoresis: taking something out of blood to work with

In order to stop alloreactive T cells

done day before or days after transplant

1. take out blood, esp WBC
2. add psoralen
3. activate w/ UV
4. put blood back in

Once photophoresis has taken and the alloreactive cells have apoptosed

The baby MQ will reverse back into immature DC (b/c they share common lineage)

Immature DC can
anergize
become Tregs (medium affinity)

These new Tregs are now specific for tumor cells b/c that's what they were

Front 27

Psoralen

Back 27

Apoptosis inducing drug that must be activated w/ Uv for photophoresis

Allows reversion of baby MQ into immature DC (anergy, Tregs)

Front 28

how does photophoresis work?

drawback?

Back 28

once psoralen induces death in the proliferating cells that are alloreactive,

the monocytes (baby MQ) will reverse develop into immature DC

Immature DC will
*anergize the new alloreactive T
*diff alloreactive into Treg

and then the new Treg will specifically suppress alloreactive T (like what it was before)

Treg conversion in periphery b/c it is of "medium-affinity"

drawback: may allow tumor to regenerate

Front 29

Screening for Hyperacute Rejection

Back 29

Not planned

ABO testing

Ab testing- cross-matching

Cross-matching:
1. take recipient serum
2. add complement proteins
3. watch for rxn

Front 30

Cross-Matching

Back 30

Testing for existence of Ab in recipient that will attack the graft

1.take recipient serum
2. add complement protein
3. watch for lysed cells

B/c if there are pre-existing Ab, they will be primarily IgG/IgM and will start classical cascade --> lysed cells

Front 31

Screening for Acute Rejection

Back 31

Planned transplant

Matching the MHC
1. sereological
2. PCR the sequence

for HLA

Front 32

Graft-Vs-Host Disease

Back 32

Graft rejects the host

Especially seen w/ bone marrow transplants

The patient is irradiated: "cleaned-out" immune system so that patient can accept new system

Patient on immuno-suppressors

The new lymphocytes from donor HSC attacking the recipient's antigens,
it is the donor cells that are alloreactive

Can be acute or chronic

Front 33

Acute GVHD

Back 33

epithelial cells undergo necrotic death and form ulcers

Front 34

Chronic GVHD

Back 34

organs will begin to atrophy

donor CTLs and NK attack the recipient's tissues

Front 35

Drugs used for transplants

3 types

Back 35

CRAM: stops T cell proliferation
(Cyclosporine, Rapamyacin, Azathriopine, Mycophenolate Mofetil)
Txt Prod of calcenurin IL-2, IL-2 signaling, IL-2 receptor, Halt T & B DNA synthesis

CAAA: Ab-T cell inhibition
(CTLA-4lg, Anti- CD40L, CD3, CD25)

Immunosuppresant: corticosteroids