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Bloc F - Defense > Mar28 M1-GVH and Rejection > Flashcards

Mar28 M1-GVH and Rejection Flashcards

1
Q

allogeneic transplant charact

A
  • host receives graft from non-self donor
  • fully or partially HLA matched
  • host is immunosuppressed to prevent GVHD or rejection
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2
Q

3 types of GVHD

A
  • after allogeneic stem cell transplant (most common)
  • following solid organ transplant (uncommon)
  • following blood transfusion (transfusion-associated GVHD) (uncommon)
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3
Q

cause of GVHD

A

donor T lymphocytes attack recipient tissues (respond to HLA I and II expressed on MHC

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4
Q

conditions for GVHD to occur (Billingham’s criteria)

A
  • graft must contain immunologically competent donor cells
  • host must be unable to reject, eliminate the donor cells of the graft (NO REJECTION)
  • host and graft must be antigenically different from each other (NOT IDENTICAL TWINS)
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5
Q

what do we mean by ‘‘graft must contain immunologically competent donor cells’’ for GVHD

A
  • mature T lymphocytes in donor
  • tolerant to self
  • intolerant to non-self HLA (major histoc complex)
  • intolerant to HLA identical molecules complexed to foreign peptides (like minor histoc complex)
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6
Q

what do we mean by host must be unable to reject, eliminate the donor cells of the graft

A
  • host is immunosuppressed

- host must be genetically identical similar to the donor (some kind of matching was done) so won’t REJECT

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7
Q

cause of GVHD after solid organ transplant (SOT)

A
  • transplant of organ with lot of mature T cells like bowel and liver
  • immune competent cells in graft attack cells in immunosuppressed host
  • these T cells will wipe out the hematopoietic cells in the BM
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8
Q

risk factors of GVHD after SOT

A
  • HLA mismatch

- older age of patient

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9
Q

clinical manifestations of GVHD after SOT

A
  • pancytopenia (bc of BM aplasia)
  • skin rash
  • fever
  • diarrhea and gut dysfunction
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10
Q

in what GVHD types do the donor T cells wipe out hematopoietic cells of the BM and in what types do they not

A
  • wipe them out in GVHD after SOT and in transfusion associated GVHD
  • don’t in allogeneic SC transplant bc the patient had no immune system in the 1st place. we’re giving them an immune system. nothing to wipe out.
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11
Q

treatment of GVHD after SOT

A

systemic steroids

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12
Q

cause of death in GVHD after SOT

A

severe cytopenias and BM failure = infections

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13
Q

why get much more rejection cases than GVHD, especially in SOT

A

it’s a question of dose. how much host has immune cells + how much host is immunocompetent VS how much immune cells are in the graft

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14
Q

% of GVHD and rejection in allogeneic SC transplant (ASCT)

A

GVHD in 20-80% of cases

rejection in 5% of cases

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15
Q

cause of TA (transfusion associated GVHD)

A
  • viable T lymphocytes in donated blood product
  • attack non HLA identical cells of the host
  • host can’t neutralize the attack bc is immunocompromised or genetically identical to the donor
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16
Q

normal transfusion conditions and why GVHD doesn’t occur

A

host (recipient) is not immunocompromised so T cells of the recipient destroy the donor lymphocytes

17
Q

what do we mean by ‘‘the host can’t neutralize the attack in TA-GVHD because it is genetically identical to the donor’’

A
  • donor HLA haplotype is AA and recipient is AB
  • recipient recognizes A of donor as self
  • donor recognizes B of recipient as foreign
18
Q

who’s at risk of having TA-GVHD

A
  • immune suppressed (disease, drug, chemo)
  • granulocyte transfusion recipient
  • premature neonate
  • partial HLA match or relative
19
Q

how TA-GVHD is avoided

A

irradiation of fresh blood products to inactivate T lymphocytes

20
Q

SCT (stem cell transplant) def

A
  • infuse healthy hematopoietic cells (SCs included) in blood stream of pt who got immunosuppressive chemo or radiation
  • replaces part or whole host BM
  • replaces an unhealthy immune system
21
Q

3 types of SCT donors

A
  • syngeneic or identical twins
  • autologous transplant (to self. in high risk lymphoma or multiple myeloma)
  • allogeneic transplant (matched)
22
Q

3 sources of stem cells (hematopoietic) for a SCT

A
  • bone marrow
  • peripheral blood
  • umbilical cord blood (extracted at birth and frozen)
23
Q

timeline of allogeneic SCT

A
  • 2 months before, match
  • 10 days before, chemo and radiation to immunosuppress host
  • after transplant, give calcineurin inhibitor for 4 months
  • CBC normal after 4 weeks (30 days)
24
Q

acute vs chronic SCT-GVHD

A
  • in first 100 days after transplant = acute
  • after 100 days after transplant = chronic
  • can be acute and then become chronic when go over 100 days
25
Q

T-F: GVHD is not reported in identical twin (syngeneic) SCT

A

True.

26
Q

3 phases of acute GVHD pathophysiology

A
  1. effects of conditioning: inflam activation
  2. donor T cell activatio: Ag directed T cell attack
  3. effector phase (cell injury, target tissue death)
27
Q

acute GVHD symptoms

A 
skin = red rash, bullae, desquamation. painful and pruritic
liver = cholestasis
gut = anorexia, nausea, vomiting, diarrhea, abd pain
NOT pancytopenia (that's in TA-GVHD or SOT-GVHD)
28
Q

how to dx acute GVHD

A

clinical picture + bx

29
Q

treatment of acute GVHD

A
  • topical therapy only in grade 1 (skin stage below 2)

- systemic steroids in grade 2+

30
Q

pathophgy of chronic GVHD

A
  • inflam, cell and humoral immunity, fibrosis

- starts like acute GVHD

31
Q

symtpoms of chronic GVHD

A

ressembles autoimmune diseases (scleroderma, Sjogren’s, PBC and PSC, immunodeficiency)

32
Q

organs where see symptoms in GVHD

A
  • skin
  • mouth
  • liver
  • eyes
  • gut
33
Q

(IMPORTANT) #1 risk factor for acute GVHD of grade >2 and also the #1 risk factor for chronic GVHD

A

HLA ressemblance (less ressemblance = higher risk)

34
Q

treatment of GVHD

A
  • systemic steroids

- therapy based on organs involved

35
Q

prognosis of aGVHD

A
  • related to grade
  • higher grade = less survival
  • 50% respond to systemic steroids
  • no response = poor prognosis
36
Q

prognosis of cGVHD

A

depends on number of organs involved and high risk factors like low platelets, poor response to steroids, progressive onset, and BSA over 50%

37
Q

good thing about GVHD

A

The worse the GVHD, the lower the chance of relapse for CML or AML
(best to worse: twin, T depletion, no GVHD, aGVHD alone, cGVHD alone, aGVHD and cGVHD)

38
Q

(imp?) first manifestation of GVHD that you see usually

A

skin involvement

39
Q

treatment of all GVHD (basically comes back to one thing)

A

systemic steroids

Bloc F - Defense (57 decks)

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