*abai: Transplant/tumor Immunology

Front 1

In kidney transplant HLA compatibility is associated with what? What drug is helpful?

Back 1

Long term survival
Cyclosporine

Front 2

What decreases GVHD in a haploidentical HSCT?

Back 2

post thymic T cell depletion

Front 3

What is cross matching?

Back 3

Mix serum from serum donor and recipient, looks for ABO/HLA incompatibility.

For acute rejection, looks for preformed antibodies

Front 4

What are features, cells/mediators and timing involved in:

Hyperacute rejection?
Accelerated rejection
Acute rejection?
Chronic Rejection?

Back 4

Hyperacute Rejection: thrombi, preformed antibodies, complement and neutrophils, minutes to hours

Accelerated Rejection: vasculitis, hemorrhage, non complement fixing antibodies, NK monocytes, hours to days

Acute Rejections:
inflammation (endovasculitis, tubulitis etc), T cells and antibodies, day to weeks

Chronic:
athlerosclerosis, onion skinning, DTH, T cells, antibodies, weeks- months

Front 5

Percentage of reactive antibodies (PRH) are important to prevent what type of rejections?

What are the risk factors?

Back 5

Hyperacute, accelerated

Multiparious women, multiple transfusions.

Front 6

What is the order of increasing risk of rejection/GVHD/nonengraftment?

Back 6

syngeneic
matched first degree relative
matched cord
matched unrelated

class II mismatch > class I mismatch
mismatched cord
mishmatched unrelated

Front 7

What are the content in early vs late tumors.

Back 7

Early - mostly hematopoeitic stem cells (lymphocytes, granulocytes, macrophages)

Late tumors - TIL (tumor infiltrating lymphocytes) CD3+ CD95+, TCR alpha/beta, and T lymphocytes

Front 8

What makes TIL (tumor infiltrating lymphocytes) associated with increased survivial?

Back 8

normal zeta chain

Front 9

What is the chance of a full match with a sibling? Half? No match?

Back 9

Full 25%
Half 50%
No match 25%

pundit square time.

Front 10

What is the difference between direct and indirect allo-recognition?

think solid organ transplant

Back 10

D = Direct = Donor
Direct - donor APC presenting donor MHC/peptide to recipient T cells (often common self peptides)

Indirect - recipient APC present donor peptide to recipient T cells (MHCII process by endocytosis)

==> leads primed T cells invading the graft

Front 11

Describe the mixed lymphocyte reaction (MLR)?

Back 11

Donor and recipient lymphocytes are cultured together. One is irradiated or given mitomycin (to prevent replication). Response is measured by H3-TDRd (radioactive).

Front 12

What constitutes a 6 vs a 10 allele match?

Back 12

HLA A, B, DR, (C, DQ)

Front 13

Define a chimera vs a mixed chimera.

Back 13

chimera is 100% graft
mixed chimera is partial engraftment

Front 14

Risk factors for non-engraftment other than HLA typing.

Back 14

NK+ worse engraftment
Old donor
Old recipient
Chronic infection
Less conditioning
Low stem cells
Host T cell function

Front 15

What SCID types do best and worst?

Back 15

ADA worst
T- B+ NK- best

Front 16

For PID, when is conditioning useful?

Back 16

When they have NK or T cells.

Front 17

What is the benefit of T lymphocyte depletion of the graft?

Back 17

less GVHD
but less graft vs leukemia

done by magnetic beads to CD34+, alemtuzumab/campath (anti CD52), agglutination and rosetting with sheep RBC

Front 18

Cytokines associated with GVHD?

Back 18

TNFa
IFNg
IL10

Front 19

Acute vs chronic GVHD:
Timing?
Mediators?
Prophylaxis?
Treatment?

Back 19

Acute
= <100 days
CD45RO T cells and neutrophils, immunosupression is prophy (cyclosporine)
treatment with steroids and immunosuppression (prednisone + cyclosporine)

Chronic
= >100 days
CD4+ cells
T depletion (prophy)
treatment with steroids and immunosuppression (prednisone + cyclosporine)

Front 20

What is the ideal time for transplant in SCID, CGD, WAS?

Back 20

SCID <3.5 mo
CGD < 5 yrs
WAS < 5 yrs

Front 21

What problem still exists in a patient with partial chimerism with WAS?

Back 21

autoimmunity

Front 22

What is the success rate with a haplo-identical T depleted transplant vs HLA identical transplant?

Back 22

55% vs 80%

Front 23

What is the order of engraftment for various cell types?

Back 23

National Tire Battery

Neutrophils - weeks
NK cells - 1 mo
T cells - 3-4 mo (CD8 before CD4)
B cells - ?

Front 24

Post HSCT, can SCIDs receive live virus vaccines?

Back 24

No

Other patients (e.g transplant for malignancy) may get most vaccines at 12 months post transplant, MMR at 24 mo, but never VZV

Front 25

Northern vs Southern vs Western blot

Back 25

Northern - RNA (size, sequence, semi-quantitative)
Southern - DNA (large size DNA)
Western - protein

Electrophoresis, transfer to membrane, immuno-assay

Front 26

What are the advantages fo FISH (flourescent in situ hybridization)?

Back 26

May be used in dead or dividing cells

THINK - dead fish

Used in digeorge, downs, ALL

Front 27

What can happen to T vs B cells if they fail central tolerance?

Back 27

B cells - receptor editing, anergy, apoptosis
(high dose/concentration of antigen more likely to develop receptor editing)

T cells - T reg, apoptosis

Front 28

What can happen to T vs B cells if they fail peripheral tolerance?

Back 28

B cells - apoptosis, anergy (once in the periphery you can't receptor edit)

T cell - T reg, apoptosis, anergy

Front 29

Name 2 inhibitory molecules on T cells that maintain anergy in T cells in the periphery.

Back 29

CTLA4
PD-1

Front 30

What 2 pathways are activated to help delete autoreactive T cells and maintain tolerance in the periphery?

Back 30

Think apoptosis:

Fas/FasL - deletes autoreactive cells through caspases

BIM - (Bcl2 protein family - pro-apoptotic) - uses mitochondria for apoptosis

Front 31

What factors are associated with tolerance?

Back 31

High dose of antigen.
Long exposure
PO or IV exposure
No adjuvant
Naive and inactivated APC

"lick your cat when young when you dont have a cold"