Pbd - Week 9

Front 1

What are 4 major contraindications to transplantation?

Back 1

1. Severe non-transplant organ dysfunction (E.g. severe heart failure in someone who needs a kidney)

2. Malignancy

3. Infection - active bacterial or precarious viral

4. Psychosocial: uncontrolled disease or likely unwillingness to adhere to treatment

Front 2

Dead donor organs must be obtained quickly to prevent warm ischemia. How is this accomplished?

Back 2

The aorta is cannulated and flushed with cold preservation solution and organs are cooled using ice slush. Once cold ischemia is induced - organs are removed.

Front 3

Ischemic injury occurs when there is depletion of ATP and production of ____. What happens when this tissue is reperfused? What is the significance for transplantation?

Back 3

Production of reactive O2 species. When blood flow returns, there is an inflammatory response, endothelial dysfunction and vosospasm.
This is a problem b/c it increases graft immunogenicity

Front 4

If 2 people have a 6/6 HLA match, does this mean they are genetically identical? Why or why not?

Back 4

6/6 match does NOT mean that they are identical because they can still be different at minor HLA loci and non-HLA loci.

Front 5

When considering the risk of graft rejection, what is more important that HLA matching?

Back 5

The presence of anti-HLA Ab's at the time of transplantation is more important than HLA matching

Front 6

How do you test for the presence of anti-HLA Ab's in a transplant recipient?

Back 6

You take a bunch of donor T and B cells and add them to the recipient's serum with some dye that cannot enter healthy cells. If the recipient serum has anti-HLA Ab's then they will bind --> activate complement --> MAC --> dye will enter the cells giving a + cross match

Front 7

Ideally you would want to avoid T-plants in people with donor-specific Ab's but this cannot always be determined pre-transplant. Why? For which organ is the crossmatch not so important?

Back 7

Cannot also do this because of short cold-ischemia time for some organs (heart, lung).
Crossmatch is not important in Livers

Front 8

Describe how the Panel reactive Ab test works (ie what's in the wells & what gets added).
In what form are results reported?

Back 8

Use a panel with ~ 50 wells and fill them with samples representative of HLA alleles in the population. Add pt serum, complement and dye. The wells that turn black represent HLA-bearing cells that can be killed by the pt's serum.
Report the # of wells that turned black as a percentage
(since the HLA samples are known you may also be able to assign specificity).

Front 9

What are 2 causes of false negatives in the Panel Reactive Ab test?
What can cause a false + ve?

Back 9

Because the test requires complement to be fixed and high levels of circulating Ab to get a reaction it is possible to get false --ves.

The test can also give false +ves because it cannot distinguish between MHC class I or II, or non-HLA Ab's.

Front 10

What crossmatching test detects the lowest levels of Ab's and has a high specificity (ie is able to distinguish between class I and II)

Back 10

Flow Citometry: mix fluorescent Ab's that will stick to IgG with the pt's serum (now the IgG's are "tagged"). Add HLA's of known specificity and check for binding.
False --ves VERY rarely!!

Front 11

What is the most common type of rejection and what is it mediated by?

If a person has a 6/6 HLA matching, is the panel reactive Ab relevant?

Back 11

Most common type of rejection is acute cellular - mediated by activated T cells.

Even with very well matched pt's (6/6 HLA), an elevated PRA is associated with worse graft oucomes. Thus the PRA remains a good marker for rejection risk

Front 12

What are the 3 signals, in the 3-signal model of T-cell activation?
*hint*

Back 12

Signal 1:
The Ag is presented to the T cell bound up in MHC

Signal 2:
The T cell CD28 : CD80 APC bind; giving the T cell co-stimulation and leading to the production of IL-2

Signal 3:
The IL-2 produced by T cell binds the Tcell CD25 receptor and this activates mTOR = cell proliferation

Hint 12

1: simple - only one that involves Ag

2: Costimulation (binding of what & what). Produces what?

3. The "what" produced above activates.....

Front 13

Describe (in basic terms) the process of acute cellular rejection.
*hint*

Back 13

Activated T cells enter the graft tissue in response to HLA
T cells release inflammatory cytokines
Directly kill cells expressing the foreign HLA

Hint 13

____ enters..........
releases.........
result? (takes 3-5days!)

Front 14

Describe in basic terms the steps involved in humoral rejection?

What determines whether this is hyperacute?

Back 14

B cells that are specific to donor HLA get activated and produce Ab's which bind ---> complement ---> cell lysis

If anti-HLA Ab's were present before Tplantation then reaction will be hyperacute.

Front 15

What type of medication is used for induction therapy?

What 3 medications are used for maintenance therapy

Back 15

Monoclonal or polyclonal Ab's with higher doses of maintenance drugs

Maintenance therapy:
Primary agent (Calcineurin inhibitor) +- antiproliferative +- steroids

Front 16

What are the 3 common findings in allograft disease?
I f
P a
O a

Back 16

1. Interstitial fibrosis
2. Parenchymal atrophy
3. Obliterative arteriopathy

Front 17

What are some of the causes of chronic allograft rejection?

Back 17

1. donor quality
2. duration of cold/warm ischemia
3. episodes of acute or subclinical rejection
4. infections in graft
5. recurrence of primary disease
6. production of Ab's
7. HTN, Hlipids
8. Toxins (EtOH, smoking, etc)
9. Is medications

Front 18

What are the 4 metabolic effects of I suppression?

In what 5 ways are these effects managed/treated?

Back 18

I-sup medications cause:
-hypertension,
-high cholesterol (mechanism unclear),
-diabetes mellitus,
-weight gain (lipid redistribution in steroids giving a “fat” face).

All of these changes ↑ risk of cardiovascular disease and need to be treated aggressively with:
Smoking cessation, exercise, weight management, Bp and lipid control, anti-platelet agents.

Front 19

Many non-renal transplant patients have abnormal renal functions at time of transplant d/t HTN/HoTN, diabetes, smoking, or a primary disease that affects the kidneys.
What are 4 causes of ARF post-transplant?

Back 19

- Intra-operative hypotension (blood loss)
- Post-op sepsis
- Nephrotoxic medications (Aminoglycosides, ACE & Calcineurin inhibitors, etc)
- Intravascular depletion due to ↓ intake or ↑ loss (diarrhea)

Front 20

Why type of vaccines require repeated boosters? (2 types)

What 2 types confer long last immunity?

Back 20

inactivated toxoids and killed viruses or subunits

Live vaccines or conjugates confer long-lasting immunity

Front 21

What vaccine was recalled because it was thought to cause intussusception?

Back 21

Rotavirus vaccine that was given orally

Front 22

What viral infection has a vaccination program that is currently ineffective (ie we see the disease in adults?

Back 22

Pertussis

Front 23

Menactra is meningitis vaccine. What 4 strains does it contain?
(it is esp. given to ppl >2yrs who are going to SSA)

Back 23

Menactra is a conjugate vaccine that contains A, C, Y and W138

Front 24

What is the difference between antigenic drift and shift?

In what type of influenza do most changes occur?

Back 24

Drift is small changes in aa
Shifts are major changes in the H & N antigens

Most changes occur in Influenza A

Front 25

The H1N1 vaccine is what type of vaccine?

Back 25

H1N1 is a conjugated subunit vaccine
(non-conjugates for pregnant women)

Front 26

What 4 types of HPV are linked to cervical cancer?

Back 26

6, 11, 16, 18,

Front 27

What blood type is the universal blood recipient? Universal blood donor?
What about for plasma?

Back 27

Blood:
recipient: AB
donor: O

Plasma
recipient: O
donor: AB

Front 28

Which is more dangerous, Ab's to ABO or non-ABO Ag's?
Why (give 3 reasons)?

Back 28

Ab's to non-ABO Ag's are less dangerous because:
-tend to occur only after an exposure (ie not spontaneous)
- short lived and rates fall over time
- poor activators of complement

Front 29

What is the cause of a delayed hemolytic transfusion reaction? when does it occur?
Symptoms? (3)

Back 29

minor blood group incompatibilites causes delayed hemolysis about 4-11days post-transfusion.
Symptoms: fever, ↓Hb and ↑ billi

Front 30

What type of Ab binds to ABO Ag? What about minor RBC Ag's?

Back 30

IgM usually binds ABO. IgM is a pentamer and can thus bind several RBC's causing agglutination.
Minor RBC Ag's are usually bound by IgG monomers which can only bind one cell at a time & thus don't cause agglutination (makes these Ab's harder to detect)

Front 31

How do you detect Ab's to minor blood groups?

Back 31

The Coomb's test! Use Anti-globulin whic are Ab's to Ab's. So, if RBC's are coated in Ab, the addition of an Anti-globulin will cause the RBC's to agglutinate = + test!

Front 32

What test would you use to determine if RBC's were coated in Ab? How about to determine if the plasma contains Ab?

Back 32

Do the RBC's have Ab?
- direct antiglob test (Coombs): mix antiglob with cells, agglutination = +

Does the plasma have Abs?
Indirect A-globulin test: plasma mixed with RBCs and them antiglob added

Front 33

Before transfusing a pt you must do a group & screen, then X-match. What is the difference between the Group and the Screen tests?

Back 33

Group: Pt's blood is checked for ABO and Rh group, while serum is checked for Ab's (via Indirect test)

Screen: Pt serum is check for alloAb's against minor blood Ag's by mixing pt plasma with a panel of RBC's + anti-globulin
(have a bunch of known, isolated RBC's in wells. Add serum (if Ab's present they will bind but won't agglutinate) then add antiglob to agglutinate any bound Ab's)

Front 34

After a Group & Screen, before transfusing you must have a cross-match test done. What does this involve?

Back 34

This test is the same as the screen except now you are testing the pt's serum against the donor RBC's rather than the standard RBC panel.
(if the group & screen showed no minor Ab's this can be abbreviated and no antiglobulin added --> in which case you're basically just confirming that there's no major Ab mis-match!)

Front 35

When stored at their ideal temperatures rank the following in order from shortest to longest shelf life:
RBC's, Plasma, Platelets

Back 35

Platelets (5days)
RBC's (42days)
Plasma (1yr when frozen, 1 day once thawed)