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Immunology > transplantation immunology > Flashcards

transplantation immunology Flashcards

1
Q

autografts

A

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

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2
Q

isografts

A

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

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3
Q

allografts (allogeneic)

A

grafts exchanged between nonidentical members of the same species

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4
Q

xenografts (zenogeneic)

A

grafts exchanged between members of different species

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5
Q

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

A

xenografts

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6
Q

HLA Ags are ____ expressed

A

co-dominantly

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7
Q

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

A

1

because every nucleated cell expresses class I

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8
Q

class 2 HLA- three most important for transplantation pairs are

A

HLA-DR

HLA-DP

HLA-DQ

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9
Q

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
A
    1. donor recipient
    2. unprocessed
    1. recipient recipient
    2. processing
    3. chronic
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10
Q

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: ____
A
  1. DAMPS
  2. foreign MHC
      1. TH2
    2. TH1
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11
Q

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 ____
A
  • mechanical
    • cold ischemia time
      • mediators
      • fibrinopeptides
      • endothelial mast
      • bradykinin
    • rejection
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12
Q

ABO matching is not important for

A

corneal transplantation

heart valve transplantation

bone and tendon grafts

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13
Q

ABO incompatibility is not a contraindication to ____ ____ transplantation

A

stem cell

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14
Q

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
A
  • fresh blood
    • anti-A serum
      • agglutination
        • A
      • anti-B serum
        • agglutination
          • B
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15
Q

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:
A
  • 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
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16
Q

MHC is termed the ____ ____ ____ , HLA complex

A

human leukocyte antigen

17
Q

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

A

polymorphism

18
Q

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 ____
A
  1. donor recipient
  2. dye Abs
  3. donor
19
Q

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
A
  1. recipient donor
  2. recipient
  3. complement
  4. dye
  5. attack
20
Q

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 ____
A
  1. donor irradiated
  2. recipient
  3. against
  4. proliferating DNA
21
Q

Host vs Graft:

  • ____ immune system recognizes and attacks ____ tissue
  • three types:
A
  • recipient donor
    • hyperacute
      • acute
      • chronic
22
Q

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
A
  • donor recipient
  • bone marrow
23
Q

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
A
  • recipient donor direct
  • days to weeks
  • donor
  • direct
24
Q

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
A
  • preformed
  • ABO
  • immediate
  • thrombosis and occlusion
25
Q

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
A
  • months to years
    • smooth ischemia
      • macrophages
      • indirect
    • reperfusion
      • disease
      • nephrootoxic (cyclosporine A)
      • damaged
26
Q

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

A

more

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

27
Q

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)
A
  • donor recipient
  • CD8+
  • lungs, liver, and intestine
  • bone marrow
  • diarreha, rash, and jaundice
  • minor histocompatibility Ags
28
Q

primary goals of immunosupression:

  1. to prevent immune rejection of transplanted tissue by ____ immune response
  2. to minimize ____ side effects and toxicities
A
  1. downregulating
  2. drugs
29
Q

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

A

blocking NFkB

30
Q

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

A

NFAT

kidneys

31
Q

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

A

T cell activation

32
Q

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

A

CD80/86

33
Q

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

A

IL-2

34
Q

corticoids:

  • are ____ glucocorticoids
  • mechanism of action:
    • blocks ____
    • inhibition of ____ proliferation
    • induction of lymphocyte ____
  • used clinically for treatment of transplant ____
A
  • anti-inflammatory
    • NFkB
      • T-cell
      • apoptosis
  • rejection
35
Q

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
A
  • CD3 signaling
  • induction
36
Q

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
A
  • fungus
  • calcium (calmodulin/calcineurin)
  • NFAT IL-2
  • organ
37
Q

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
A
  • streptomyces spp
  • calcium (calmodulin/calcineurin)
  • NFAT IL-2
  • acute
38
Q

calcineurin inhibitors are associated with ____ toxicity leading to graft loss

A

kidney

39
Q

CTLA4-Ig fusion protein:

  • binds ____ blocking ____ co-stimulation of T cells
A
  • CD80/86 CD28

Immunology (23 decks)

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