Transplantation

Question 1

What is the indirect pathway of allorecognition?

Answer 1

Uses MHCII

1. Donors MHC is processed in APC of the recipient.
2. The donor MHC are presented as MHCII molecules

Question 2

Which pathway is seen with chronic rejection?

Answer 2

Indirect pathway

Question 3

What is hyper acute rejection?

Answer 3

1. Minutes to hours

2. Via preformed anti donor anditbodies and complement factors

Question 4

What is accelerated rejection?

Answer 4

1. Occurs in days

2. Reactivation of sensitized T cells

Question 5

What is an acute rejection?

Answer 5

1. Occurs in days to weeks

2. Consists of primary activation f T cells

Question 6

What is a chronic rejection?

Answer 6

1. Occurs over months to years
2. Caused by immunological and non-immunologic factors.
3. Not manageable with immunosuppressants

Question 7

Which type of cells cause cellular acute rejection?

Answer 7

Th1

Question 8

What type of cells cause humoral acute rejection?

Answer 8

Th2

Question 9

Explain what a hyper acute graft rejection is.

Answer 9

Pre-existing antibodies of the recipient (specific to the donor) already exist. Causing complement activation, endothelial damage, inflammation, thrombosis within minutes to hours.

Question 10

What are different possibilities that can lead to hyperacute graft rejection?

Answer 10

1. ABO blood group incomparable
2. Recipient is sensitized to donor MHC (recipient T cells convert memory of previous exposure)
3. Classical complement activation
4. Endothelial death via complement

Question 11

What cells have a primary role in acute graft rejection?

Answer 11

The donor DCs of passenger leukocytes

Question 12

When is a primary immune response generated in an acute graft rejection and where does this occur?

Answer 12

1. Primary immune response occurs when donor DC drain from the transplanted organ to the LN, and cause cell activation

Question 13

What happens in acute graft rejection after the primary immune response is initiated?

Answer 13

1. T cells migrate to donor organ and cause tissue damage.

2. Caused by CD4/CD8+ T cells

Question 14

What are the 2 ways that tissue damage can occur in acute graft rejection after the primary immune response occurred?

Answer 14

1. CTL generation

2. Induce delayed-type hypersensitivity reaction

Question 15

What is a common cause of chronic rejection?

Answer 15

1. Occlusion so far blood vessels causes organ ischemia

Question 16

What are common non-immunologic factors contributing to chronic graft rejection?

Answer 16

1. Ischemia-reperfusion damage
2. Disease recurrence
3. Nephrologist drug effect

Question 17

What is the normal pathway activated with chronic rejection?

Answer 17

Indirect pathway, which normally includes Abs

Question 18

What are key concepts of the graft tissue?

Answer 18

1. Condition of the allograft
2. Donor-host antigenic disparity
3. Strength of host anti-donor response
4. Immunosuppressive regiment

Question 19

What acts as a non-immunological factor that increases local vascular permeability?

Answer 19

1. Increase fibrinopeptides.
2. From the clotting cascade and fibrin formation
3. Also neutrophil and macropahge attractant

Question 20

What are the early inflammatory processes that can cause allograft rejection if not properly managed?

Answer 20

1. Fibrinopeptides to form clot

2. Production of bradykinin to cause vasodilation/ vascular permeability

Question 21

What are the stages of the donor-recipient work up before transp;ant action?

Answer 21

1. ABO blood group compatibility
2. Tissue typing (HLA inspection)
3. cross match recipient serums for preformed Abs against donor
4. Mixed lymphocyte reaction determines donor cells proliferation of the recipient lymphocytes

Question 22

Where is ABO blood matching not important?

Answer 22

1. Cornea transplants
2. Heart valve transplants
3. Bone/tendon grafts

Question 23

Why is ABO not contraindicated with stem cells?

Answer 23

No specificity has occurred yet in the stem cells

Question 24

A red blood cell type A, will express which Abs, and which Ags?

Answer 24

Ab: Anti-B
Ag: A

Question 25

A red blood cell with ABO type B express Ag/Ab of which kind?

Answer 25

Ag: B Ab: anti-A

Question 26

Group AB blood type will express what kind of Ag/Ab?

Answer 26

Ag: A and B Ab: neither

Question 27

Group O will express which kind of Ag/Ab?

Answer 27

Ag: none Ab: Anti-A, Anti-B

Question 28

What type of blood can A type receive?

Answer 28

Type A or O

Question 29

What type of blood can Type B receive?

Answer 29

Type B and O

Question 30

What type of blood can AB receive?

Answer 30

Can receive type A, B, O

Question 31

What type of blood can type O receive?

Answer 31

Can only receive type O

Question 32

What was the classical method of serological HLA testing?

Answer 32

Use of complement dependent serology (Like in micro with sheep RBC)

Question 33

What is cross-matching used to test for?

Answer 33

Test's the recipient serum for preformed ABs against the donor's HLA's which would cause rejection

Question 34

What can be used to determine if the donor cells stimulate proliferation of teh recipient's lymphocytes?

Answer 34

Mixed lymphocyte reaction (HLA II typing)

Question 35

What is HLA II typing, mixed lymphocyte reaction?

Answer 35

1. Determines the donor cells ability to stimulate proliferation of the recipient lymphocyte

Question 36

When will no cell proliferation occur in a class II HLA typing reaction?

Answer 36

If the MHC II are the same then no proliferation will occur

Question 37

When will cell proliferation occur in a HLA II typing mixed lymphocyte reaction?

Answer 37

If MHC II Ag are not the same, proliferation will occur

Question 38

What type of response is a host versus graft?

Answer 38

Adaptive immune. When host attacks the donor tissue

Question 39

What makes a host versus graft resposne rapid and dangerous?

Answer 39

Better than against a pathogen, bc of increased number of T cells recognizing foreign material.

Question 40

What mechanisms have a large effect of activation of graft rejection?

Answer 40

1. Humoral rejection (Th2: IL-4,-5,-10) | 2. Cellular rejection (Th1: IL-2, IFN-gamma)

Question 41

What is the primary role for chemotherapy while trying to generate hematopoietic stem cells?

Answer 41

1. Prevent graft rejection 2. Create niche for the HSC engraftment 3. reduce tumor cells when stem cells are used to treat cancer

Question 42

What is the direct pathway of allorecognition?

Answer 42

1. The donor's MHC molecules are recognized by the recipient's T cells and cause activation 2. Seen only with Type I MHC