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PDAT4 > Week 6 Recitation - Allograft Recognition > Flashcards

Week 6 Recitation - Allograft Recognition Flashcards

1
Q

Cellular Rejection

A

Th1 Mediated

Kidney is constantly producing FOREIGN AG’s
VVVV
Taken by DENDRITIC CELL (apc)
VVV
T-CELL ACTIVATION
CD4+ Th produces cytokines –> activate/proliferate other leukocytes
CD8+ Tc –> directly damage AG source

Cellular Rejection

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2
Q

Humoral Rejection

A

Th2-Cell
VVVV
B-CELL ACTIVATION
differentiate into AB producing Plasma cells
VVVV
ANTIBODIES + COMPLEMENT SYSTEM

Humoral Response

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3
Q

Direct & Indirect
Allo-Recognition

A

T-Cell Activation by the APC (dendritic cell)
is ESSENTIAL FIRST STEP

  • *Direct**
  • *APC = Donor Derived**
  • *Indirect**
  • *APC = Recipient Dirived**

Both ultimately do the same thing!

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4
Q

Indirect Allograft Rejection Pathway

CD8+ Tc Path

A

APC is RECIPIENT Derived

  • Recipient APC recognizes Kidney Cells
  • APC encounters CD8 T-Cytotoxic Cells –> ACTIVATED
    • –> Proliferation of CD8 Tc
    • –> Reach the RENAL BLOOD VESSEL (kidney)
      • KILL / DESTROY cells that are carrying the ANTIGEN
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5
Q

Indirect Allograft Rejection Pathway

CD4+ Th Path

A

APC is RECIPIENT Derived

  • Recipient APC encounters CD4 Th Cells –> ACTIVE
    • –> proliferation of CD4 Th
  • Th1 –> produces Cytokines IL-2 / INF-y
    • IL-2 –> stimulates proliferation of all cells = CD8 + CD4
    • INF-y –> INCREASE MHC expression on endothelial cells + renal tubules
      • –> more MHC to present AG for CD8
      • also ACTIVATE MACROPHAGES –> assist Th cells
  • IF ENVIRONMENTAL FACTORS ARE CORRECT = Th1 –> Th2
    • ​Th2–> activatesB-cell
      • –> bcomes a PLASMA CELL
        • –> PRODUCE AB’s –> ENDOTHELIAL DMG to RENAL BLOOD VESSEL
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6
Q

Direct Allograft Rejection Pathway

A

APC is from DONOR

  • We dont just transplant the KIDNEY
    • ​we also transplant OTHER CELLS like APC’s
  • DONOR APC –> migrates OUT OF THE KIDNEY –> LYMPHOIDS
    • Encounters naive CD8 or CD4
      • then body responds the same way as INDIRECT pathway
      • occurs REGARDLESS if the APC is from donor or recipient​​
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7
Q

Three Signal Model of T-Cell Activation

A

Need the
Costimulatory Signal = #2
from
B7** (APC) & **CD28 (T-Cell)

in order for
Signal Transduction

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8
Q

Rejection Types & Timing

A

HYPERACUTE Rejection
Minutes
Failure to IDENTIFY Pre-Existing DONOR AB (DSA)

Below is a Failure of Immunosuppresive Therapy

Acute Rejection
Days-Weeks

Late-Acute Rejection
> 3 months

Chronic Rejection

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9
Q

What influences Rejection Risk for ORGAN TYPES?
Determining Rejection Risk

A

Organs that are:
Very rich in LYMPHOID TISSUE = HIGHER RISK of rejection
because a Higher Population of APC’s are transplanted w/ organ

LUNG / SMALL BOWEL
>
Heart
>
Kidney / Pancreas
>>
Liver (lowest risk)

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10
Q

Which Organ has the HIGHEST risk for REJECTION?

A

LUNG / SMALL BOWEL

Organs rich with lymphoid tissue = higher risk
due to APC’s transplanted w/ organ

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11
Q

Which ORGAN has the lowest risk for REJECTION?

A

LIVER

Less lymphoid tissue = lower risk for rejection
less APC’s are transplanted w/ organ

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12
Q

Rejection Risk
ABO BLOOD TYPES

A

Blood Group Mismatch for a DECEASED DONOR TRANSPLANT
is an ABSOLUTE CONTRAINDICATION

For living patient, due to organ shortage:
this can be overcome for LIVING KIDNEY DONOR but at HIGH RISK

AB = Universal RECIPIENT

O = Universal dOnor

A = Can only take A or O

B = Can only take B or O

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13
Q

What type of ORGAN DONOR can
OVERCOME ABO BLOOD TYPE MISMATCH?

A

LIVING KIDNEY DONOR

Due to severe organ shortage

but they are considered at VERY HIGH RISK for rejection
need STRONGEST Immunosuppression

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14
Q

HYPERACUTE Transplant REJECTION

A

Occurs in MINUTES = worst case scenario

ANTIBODY MEDIATED REJECTION
VVVV
COMPLEMENT ACTIVATION
AG-AB complexing

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15
Q

Rejection Risk
on PREVIOUS EXPOSURE to FOREIGN AG = HLA

A

Antibodies AGAINST HLA
Since RBC’s are NOT nucleated –> do NOT communicate with cell markers
but All other cells present HLA’s

Only These HLA-Types are VERY IMMUNOGENIC
HLA - A
HLA - B
HLA - DR (MHC2)

ABSOLUTE CONTRAINDICATION for
DECEASED Donor Transplants

May be overcome for Living RENAL Donor

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16
Q

3 THINGS THAT RESULT IN DSA (HLA Antibody) PRODUCTION

A
  • Ab’s** to HLA are *NOT naturally occuring
  • unlike blood group AB’s*

BLOOD TRANSFUSION

PREGNANCIES
HLA from the FATHER

Previous ORGAN/TISSUE TRANSPLANTS

17
Q

Which HLA-Types are important for TRANSPLANTS

A

These are all very IMMUNOGENIC

HLA - A

HLA - B

HLA - DR
MHC2

18
Q

What do you call it when there is
2 HLA Matches?
Ex.
Both patients have:
HLA - B27 & HLA - DR36

A

2/6 in the HLA MATCH

OR

4/6 in the HLA-MISMATCH

19
Q

What type of ORGAN DONOR can OVERCOME
DSA MISMATCH

A

DSA = Donor-Specific HLA Antibody

LIVING RENAL = KIDNEY DONOR

Due to organ shortage, we can do this

ABSOLUTE CONTRAINDICATION
for deceased donor transplants for:
Kidney / heart / lung / livers

20
Q

How to we PREDICT REJECTION RISK?
Based on DSA, before finding a donor.

A

PRA = Panel Reactive Antibody

Estimates BOTH:
Rejection RISK & WAIT TIME
evaluated every 1-3 months

Measures the:

  • *# of Pre-Formed DSA** in
  • *Potential Recipient vs RANDOM POOL of HLA from GEN-POP**
  • *High PRA = >30%**
  • *SENSITIZED = High Risk for Rejection**
21
Q

PRA

What does it measure?
And against what?

A
  • *Panel Reactive Antibody**
  • *Test to PREDICT REJECTION RISK**

Measures:
Amount of Pre-Formed HLA AB (DSA)
in Potential Recipient
vs
Random pool of HLA from GENERAL POPULATION

Higher PRA –> Greater Waiting Time
>30 = sensitized & @high risk

22
Q

What test do we use to PREDICT REJECTION RISK
AFTER we find a UNIQUE DONOR?

A

CROSSMATCH = XM

Determines the immunologic compatibility between:

  • *Donor & Recipient**
  • *before EVERY TRANSPLANT**

Measures:
the immune response (HLA Ab) that the RECIPIENT has
to his/her UNIQUE DONOR (HLA Ag)

NONE/NEGATIVE is what we want
not specific to WHICH ab is present

23
Q
  • *Crossmatch = XM**
  • *TEST**
A

Negative** or **NONE
is the result we want

Measures the:
Immune Response Recipient = HLA Antibody
has to
His/Her Unique Donor = HLA Antigen

Test is NOT specific for WHICH AB is present
not DSA specific

24
Q

What does it mean to have a
POSITIVE CROSSMATCH RESULT?

A

Positive = BAD –> Poor Outcome

If Deceased Donor Transplant –> CANCELLED
organ moves to next person on list

Due to severe organ shortage,
May be OVERCOME in case of
Living Kidney Donor and Rarely in Heart transplant
HIGH RISK

25
Q

Is there a DSA Specific test?

A

YES
Crossmatch is NOT SPECIFIC

But it is EXPENSIVE & OPTIONAL

Used AFTER TRANSPLANT to monitor for appearance of
de-novo DSA

26
Q

What type of ORGAN DONOR can OVERCOME
a POSITIVE CROSSMATCH RESULT?

A

LIVING KIDNEY DONOR
and
in some cases Heart Transplants

Due to severe organ shortage

Positive = Recipient has Pre-formed DSA
HIGH RISK or rejection

PDAT4 (34 decks)

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