transplantation immunology

Question 1

autografts

Answer 1

grafts exchanged from one part to another part of the same individual

Question 2

isografts

Answer 2

grafts exchanged between different individuals of identical genetic constitutions (e.g. identical twins)

Question 3

allografts (allogeneic)

Answer 3

grafts exchanged between nonidentical members of the same species

Question 4

xenografts (zenogeneic)

Answer 4

grafts exchanged between members of different species

Question 5

what type of grafts are especially susceptible to rapid attack by naturally occuring Abs and completment

Answer 5

xenografts

Question 6

HLA Ags are ____ expressed

Answer 6

co-dominantly

Question 7

polymorphisms in class ____ HLA Ags are particularly strong barriers to transplantation

Answer 7

1

because every nucleated cell expresses class I

Question 8

class 2 HLA- three most important for transplantation pairs are

Answer 8

HLA-DR

HLA-DP

HLA-DQ

Question 9

allograft recognition: direct vs indirect:

1. direct
   
   1. ____ APC → ____ T cell
      
      1. recipient T cell recognizes the ____ foreign MHC found on the donor APC
2. indirect
   
   1. ____ APC (with processed MHC from donor tissue) → ____ T cell cell
   2. the key part of this pathway is the ____ of Ag by MHC
   3. ____ rejection

Answer 9

1. 1. donor recipient
   2. unprocessed
2. 1. recipient recipient
   2. processing
   3. chronic

Question 10

host vs graft:

1. non-immune injury to graft → generation of ____
2. host T-cells enter the allograft and recognize ____ ____
3. cytokine field amplifies entire process
4. two types of rejection
   
   1. humoral: ____
   2. cellular: ____

Answer 10

1. DAMPS
2. foreign MHC
3. 4. 1. TH2
   5. TH1

Question 11

non-immunological factors (condition of allograft) that impact transplant outcomes:

• damaged grafts ( ____ trauma and ischemia-reperfusion injury)
  
  • ____ ____ ____ : time an organ is without blood circulation and is kept cold from the time the organ is removed from the donor to the time it is transplanted into the recipient
    
    • when transplanted, damaged graft tissues release ____ which trigger several biochemical cascades leading to immediate tissue damage
      
      • release clotting factors ( ____ )
      • fibrinopeptides actviates ____ cells and ____ cells (chemoattractant)
      • ____ results in vasodilation
    • can lead to ____

Answer 11

• mechanical
  
  • cold ischemia time
    
    • mediators
    • fibrinopeptides
    • endothelial mast
    • bradykinin
  • rejection

Question 12

ABO matching is not important for

Answer 12

corneal transplantation

heart valve transplantation

bone and tendon grafts

Question 13

ABO incompatibility is not a contraindication to ____ ____ transplantation

Answer 13

stem cell

Question 14

testing for ABO blood group:

• fresh blood
  
  • anti-A serum
    
    • ____ occurs (due to complement )
      
      • type ____ blood
  • anti-B serum
    
    • ____ does not occur
      
      • not type ____ blood

Answer 14

• fresh blood
  
  • anti-A serum
    
    • agglutination
      
      • A
    • anti-B serum
      
      • agglutination
        
        • B

Question 15

ABO compatibility chart:

• type A
  
  • compatible washed RBCs:
  • compatible plamsa:
• type B
  
  • compatible washed RBCs:
  • compatible plamsa:
• type AB
  
  • compatible washed RBCs:
  • compatible plamsa:
• type O
  
  • compatible washed RBCs:
  • compatible plamsa:

Answer 15

• type A
  
  • A and O
  • A and AB
• type B
  
  • B and O
  • B and AB
• type AB
  
  • A, B, AB, and O
  • AB
• type O
  
  • O
  • A, B, AB, and O

Question 16

MHC is termed the ____ ____ ____ , HLA complex

Answer 16

human leukocyte antigen

Question 17

HLA compatibiity between donor and recipient it required due to the extreme ____ of HLA

Answer 17

polymorphism

Question 18

MHC I Microtoxicity Test:

1. ____ cells + ____ serum
2. complement will form and ____ accumulates in cells ( ____ present
3. no dye accumulation (Abs are not present) → potential ____

Answer 18

1. donor recipient
2. dye Abs
3. donor

Question 19

preformed Ab testing: Microtoxicity test:

1. tests for ____ Ab against ____ HLA
2. donor cells are isolated and ____ serum (containing Ab) is added
3. ____ is added (if recipient Ab is specific for donor cells, classical complement pathway is activated)
4. ____ is added (if complement is ativated, dye enter cells via pore created by MAC)
5. if cell cytoplasm is stained, that means the recipient Abs will ____ donor cells

Answer 19

1. recipient donor
2. recipient
3. complement
4. dye
5. attack

Question 20

HLA Class II typing - mixed lymphocyte response:

1. isolated ____ cells (presumably APCs since they have MHC II) are ____ so they are incapable of proliferated)
2. ____ cells (that are capable of proliferating) are added in addition to radiolabeled thymidine
3. (usually lymphocytes that are strongly reactive to self MHC are eliminated during development) if non-recipient MHC class II is introduced, recipient lymphocytes can react to it since they were never tested ____ it
4. this is detected as the ____ recipient cells will incoporate the radiolabeled thymidine into their ____

Answer 20

1. donor irradiated
2. recipient
3. against
4. proliferating DNA

Question 21

Host vs Graft:

• ____ immune system recognizes and attacks ____ tissue
• three types:
  

Answer 21

• recipient donor
• • hyperacute
    
    • acute
    • chronic

Question 22

graft vs host:

• ____ immune cells that “piggy back” in with the transplant recognize, proliferate, and attack the ____
• mostly occurs in transplantation of ____ ____ as it will produce donor immune cells in the recipient

Answer 22

• donor recipient
• bone marrow

Question 23

acute graft rejection (HvG):

• ____ T cells recognize and attack ____ tissue (primarily foreign MHC - ____ rejection)
• occurs within ____ to ____) (T cells need to be exposed to donor Ag and have time to activate
• ____ DCs (via MHC class II mismatch) found in the transplanted tissue can also stimulate recipient immune system (direct rejection)
• primarily ____ rejection, although indirect mechanism can occur as well

Answer 23

• recipient donor direct
• days to weeks
• donor
• direct

Question 24

hyperacute graft rejection (HvG):

• ____ Abs recognize and attack transplanted Ags (humoral rejection)
• mechanism of ____ rejection (mechaism for other reactions)
• reaction is ____ (minutes to hours) and can even occur during the transplant)
• presents with ____ and ____ of graft vessels

Answer 24

• preformed
• ABO
• immediate
• thrombosis and occlusion

Question 25

_chronic graft rejection (HvG):_ * occurs within ____ to ____ following transplantation * immune mediated: * caused by fibrosis/thickening of ____ muscle in vessels supplying donated tissue resulting in \_\_\_\_ * ____ play a large role * primarily ____ rejection * non-immune mediated: * ischemia-\_\_\_\_ damage * recurrence of the ____ that caused failure of organ * the effects of ____ drugs * transplanted tissue was ____ during transplantation and that damage progreses over time

Answer 25

* months to years * * smooth ischemia * macrophages * indirect * * reperfusion * disease * nephrootoxic (cyclosporine A) * damaged

Question 26

the immune response against a graft is more or less vigorous than the response seen against a pathogen?

Answer 26

more (due to higher frequency of T cells that recognize the graft as foreign)

Question 27

_graft vs host rejection:_ * ____ immune cells recognize and attack ____ Ag (combination or donor APCs and T cells involved) * ____ T cells are mostly responsible for tissue damage via Fas/FasL interaction * this is more likely in tissues that have more resident immune cells such as ____ , ____ , and \_\_\_\_ * most commonly seen with ____ \_\_\_\_ transplants * presents with ____ , ____ , and \_\_\_\_ * reaction is directed against ____ \_\_\_ ____ of the recipient (HLA Ags are usually match)

Answer 27

* donor recipient * CD8+ * lungs, liver, and intestine * bone marrow * diarreha, rash, and jaundice * minor histocompatibility Ags

Question 28

_primary goals of immunosupression:_ 1. to prevent immune rejection of transplanted tissue by ____ immune response 2. to minimize ____ side effects and toxicities

Answer 28

1. downregulating 2. drugs

Question 29

steriods (specifically glucocorticoids) generally suppress immune response as part of their function by

Answer 29

blocking NFkB

Question 30

cylcosporine A and tacrolimuns prevent T cell activation by blocking ____ pathway (production of IL-2 included in this); this toxic to ____ and can lead to kidney transplatnation rejection

Answer 30

NFAT kidneys

Question 31

OKT3 (anti-CD3 mAb) blocks CD3, a component of the TCR complex, preventing

Answer 31

T cell activation

Question 32

CTLA-4-Ig fusion protein binds to ____ blocking CD28 co-stimulation of T cells

Answer 32

CD80/86

Question 33

Anti-CD-25 mAB blocks ____ signaling inhibiting T cell proliferation and survival

Answer 33

IL-2

Question 34

_corticoids:_ * are ____ glucocorticoids * mechanism of action: * blocks \_\_\_\_ * inhibition of ____ proliferation * induction of lymphocyte \_\_\_\_ * used clinically for treatment of transplant \_\_\_\_

Answer 34

* anti-inflammatory * * NFkB * T-cell * apoptosis * rejection

Question 35

_anti-CD3 mAB (OKT 3):_ * blocks ____ signaling in T-cells * used for ____ theapy (therapy administered at the time of organ transplantation) and treatment of acute or steriod-resistant rejection

Answer 35

* CD3 signaling * induction

Question 36

_cyclosporine A (CsA):_ * is a peptide isolated from the ____ species * inhibits ____ dependent pathway of T-cell activation * inhibits translocation of ____ into the nucleus which inhibits transcription of \_\_\_\_ * used for immunoprophylaxis as a basic component of most immunosuppressive protocols in all types of ____ transplants

Answer 36

* fungus * calcium (calmodulin/calcineurin) * NFAT IL-2 * organ

Question 37

_tacrolimus:_ * is a macrolide lactone islated from ____ \_\_\_\_ bacteria * inhibits the ____ dependent pathway of T-cell activation * inhibits the translocation of ____ to the nucleus which inhibits transcription of \_\_\_\_ * used in all type of organ transplants for induction and maintenance immunoprophylaxis and treatment of ____ rejection

Answer 37

* streptomyces spp * calcium (calmodulin/calcineurin) * NFAT IL-2 * acute

Question 38

calcineurin inhibitors are associated with ____ toxicity leading to graft loss

Answer 38

kidney

Question 39

_CTLA4-Ig fusion protein:_ * binds ____ blocking ____ co-stimulation of T cells

Answer 39

* CD80/86 CD28