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GBA Immunology > Week 13 - Transplantation Immunology > Flashcards

Week 13 - Transplantation Immunology Flashcards

1
Q

Transplantation Definition:

A

a medical procedure in which cells, a tissue or an organ is removed from the donor’s body and placed in the body of a recipient.

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2
Q

Donor Definition:

A

The person who is giving the graft (cells, tissue or organ)

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3
Q

Recipient Definition:

A

the person who is receiving the graft

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4
Q

Graft Definition:

A

the transplanted cells, tissue or organ

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5
Q

Orthotopic Transplantation Definition:

A

The graft is placed to the original anatomic location

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6
Q

Heterotopic Transplantation Definition:

A

The graft is placed to another location (different from the original anatomic location)

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7
Q

Autotransplantation Definition:

A

The donor and the recipient is the same person.

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8
Q 
Presumed consent (opting out)
Strong version:
A

no need to get a permission of the relatives

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9
Q 
Presumed consent (opting out)
Weak version:
A

with the agreement of the relatives

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10
Q

Living will (opting in, contracting in): Involves -

A

Donor Card system

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11
Q

Place the Organs in order of the frequency of transplantation:
Liver, Heart, Kidney, Pancreas, Intestine, Lung

A

1) Kidney
2) Liver
3) Heart
4) Lung
5) Pancreas
6) Intestine

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12
Q

The ACTUAL most frequent transplantation is :

A

Transfusion

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13
Q

What is an Isograft (syn-graft)?

A

Graft donation between Monozygotic twins.

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14
Q

What is an allograft?

A

Graft donation between Non-Twins.

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15
Q

What is an autograft?

A

Graft donation - Host and Donor are the same Person.

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16
Q

What is a xenograft?

A

Graft donation - from non-human organism.

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17
Q

Primary and Secondary Rejection:

What is the difference?

A

Primary - 14 days till necrosis

Secondary - 6 days till Necrosis

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18
Q

Primary and Secondary Rejection:

What are the key players?

A

• CD4+ T cells : CD4+-CD8+ cooperation is also important.

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19
Q

Histocompatibility between donor and recipient:

MHC Reaction? By?

A

Strong and Rapid
• HLA-A
• HLA-B
• HLA-DR

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20
Q

Minor histocompatibility antigens ?

Reaction?

A

slower and milder
• H-Y (Y chromosome)
• HA-1～HA-5 non Y chromosome

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21
Q

Name 3 tissue specific antigens:

A
  • ABO, Rh blood groups
  • VEC (vascular endothelial cell) antigen system
  • SK (Skjelbred ) antigen
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22
Q

Blood group antigens are also present on ______ _____ ________ ____ .

A 
Blood group antigens are also present on blood vessel
endothelial cells (as part of the donor tissue) !
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23
Q

Differences between organ and bone marrow stem cell
transplantation:
In Which one there is a cytoablation Needed?

A

bone marrow stem cell transplantation

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24
Q

Differences between organ and bone marrow stem cell
transplantation:
In Which one there is an Immune suppressive therapy is Needed?

A

organ transplantation

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25
Q

Differences between organ and bone marrow stem cell
transplantation:
In which one there is a HLA matching needed?

A

BOTH

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26
Q

Differences between organ and bone marrow stem cell

transplantation: Possible Major Complication of each?

A

Organ Transplantation Complication - Rejection

B.M Stem Cell Transplantation Complication - GVHD

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27
Q

Differences between organ and bone marrow stem cell

transplantation: Possible Success of each?

A

Organ Transplantation Success: acceptance

B.M Stem Cell Transplantation Success: tolerance

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28
Q

What is GVHD?

A

GVHD - Graft Versus Host: Proliferation of Anti-Host cells that attack the defenseless Host!

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29
Q

What is HVGD?

A

HVGD- Host Versus Graft: Proliferation of Anti-Graft cells that attack the Graft! (Rejection)

30
Q

Transplantation of Islet of Langerhans: How?

A

Purified Islets Injected with Catheter to the Portal vein and Make the Liver Sinusoids their New Home!

31
Q

“HLA matching is not an absolute prerequisite, but it helps to prevent side effects of the local steroid therapy.” For Which Transplantation is that true?

A

Cornea Transplantation

e.g. glaucoma and cataracts

32
Q

____ of T cells recognizing conventional antigens

recognize allogeneic MHC molecules.

A

1-10% of T cells recognizing conventional antigens

recognize allogeneic MHC molecules.

33
Q

What are the cells that cause Alloreactivity Initiation in Rejection Process?

A

Host and Donor Dendritic Cells

Antigen Presentation to the Lymph Node residing T cells.

34
Q

Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Allogeneic MHC State

A

Direct Recognition: Intact allogeneic MHC or in Peptide COMPLEX.
Indirect Recognition: Peptide of allogeneic MHC.

35
Q

Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Cells presenting source - Donor/Recipient

A

Direct Recognition: DONOR CELLS (“D-D”).

Indirect Recognition: RECIPIENT CELLS.

36
Q

Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Activated T cell

A

Direct Recognition: CD8+ and/or CD4+ T cells

Indirect Recognition: CD8+ and/or CD4+ T cells

37
Q

Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Role in the rejection

A

Direct Recognition: Acute Rejection

Indirect Recognition: Chronic Rejection

38
Q

Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Extent of Rejection

A

Direct Recognition: Intense (Acute Rejection)

Indirect Recognition: Mild (Chronic Rejection)

39
Q

Types of host versus graft reaction (HVG): Timing of Each -Hyperacute, Acute, Chronic

A
  • Hyperacute rejection: within minutes-hours
  • Acute rejection (humoral or cellular): < 1month
  • Chronic rejection: months - years
40
Q

Hyperacute rejection, Mechanism by Antibodies for “

A
  • ABO blood group antigens
  • VEC (vascular endothelial cell) antigen
  • HLA antigens
41
Q

Origin of HLA sensitization - Try to Remember at Least 4 Examples

A
  • Transfusion
  • Pregnancy
  • Previous transplantation
  • Others (e.g. undetected spontaneous abortion, semeninduced antigen stimulation, cross-reactive microbes)
42
Q

What is the main cause of Necrosis of the Graft in Hyperacute Rejection?

A

Thrombotic closure of graft vessel Ischemia.

43
Q

What is the cause of the Thrombotic events in Hyperacute Rejection?

A

Complement System activation with Endothelial Damage.

44
Q

Acute Rejection Types:

Humoral: vasculitis - Cause?

A

• Alloreactive IgG binds to the endothelial cells causing

endotheliitis.

45
Q

Acute Rejection Types:

Cellular: parenchymal damage - Cause?

A

Direct allogeneic MHC/peptide complex recognition
• DTH (CD4+Th1)
• CD8+Tc mediated cell damage

46
Q

Alterations of Chronic Rejection (3):

A
  • Fibrosis
  • Vascular sclerosis
  • Decline in the graft function
47
Q

Chronic Rejection: Mechanism

A

• Chronic inflammation with CD4+T cells and
macrophages
• Degenerative changes of the transplanted organs
due to non-immune factors

48
Q

General approaches of prevention of transplantation rejection: Donor Selection Types (2)

A

• Live donor – relative: there is sufficient time for
genotyping
• Cadaver: transplantation list

49
Q

General approaches of prevention of transplantation rejection: Ex vivo graft manipulation - How are
Immunocompetent cells being eliminated?
(At least 4 Examples)

A
  • Steroid infusion of the graft prior to transplantation
  • Tolerance induction
  • Anti-CD28
  • Anti MHC II
  • Anti-CD4
50
Q

General approaches of prevention of transplantation rejection: Possible helpful manipulation on Host

A

Immunosuppression

51
Q

How to Glucocorticoids aid in Immunosuppression?

A

Competitive Transcription factors causing inhibition of Cytokine production (NFkB pathway Competitive)

52
Q

4 examples for Immunosuppressants:

A
  • CTLA4-Ig (Against B7-CD28 Interaction)
  • Cyclosporine (Against Calcineurin)
  • Rapamycin (Against mTOR)
  • Anti-TCR
  • Anti-IL-2R
53
Q

Multiple Myeloma, AML, Amyloidosis, CML, Sickle cell Disease are all examples for diseases that are treated with ___ _______.

A

Multiple Myeloma, AML, Amyloidosis, CML, Sickle cell Disease are all examples for diseases that are treated with HSC transplantation.

54
Q

Hematopoietic stem cell (bone marrow)

transplantation is used (among other uses) for ____________ of hematopoiesis after ______ ________therapy.

A

Hematopoietic stem cell (bone marrow)
transplantation is used (among other uses) for Reconstitution of hematopoiesis after chemo- and/or
radiotherapy.

55
Q

Leukapheresis is used to obtain stem cells from _______ blood

A

Leukapheresis is used to obtain stem cells from peripheral blood

56
Q

DLI: What is it for?

A

Donor lymphocyte infusion (DLI) – to treat relapse of Leukemia

57
Q

MRD: What is it? Importance?

A

Minimal residual disease: small numbers of leukemic cells that remain in the person during treatment, or after treatment when the patient is in remission (no symptoms). It is the major cause of relapse!

58
Q

Which of these is a description of a patient with HSC Donation: (Also point to monitor)
Mixed Chimera / Complete Chimera

A

Mixed Chimera

Monitoring of MRD is critical here - Leukemia Relapse!

59
Q

Which of these is a description of a patient with DLI: (When is it given)
Mixed Chimera / Complete Chimera

A

Complete Chimera

Given after Mixed Chimera State - Prevention of Leukemia Relapse!

60
Q

Conditions in which GVHR develops:
• Sufficient number of ___________ cells in the
graft
• _______ in immune defense in the recipient
• ____ differences between the host and the graft

A

• Sufficient number of immunocompetent cells in the
graft
• Decline in immune defense in the recipient
• MHC differences between the host and the graft

61
Q

Graft versus host reaction (GVHR) may occur in:
• After bone marrow stem cell transplantation
• After _____ transplantation
• After ______ transplantation
• After _____ blood transfusion
• Solid organ transplantation (lung, liver, small intestine)

A

Graft versus host reaction (GVHR) may occur in:
• After bone marrow stem cell transplantation
• After thymus transplantation
• After spleen transplantation
• After neonatal blood transfusion
• Solid organ transplantation (lung, liver, small intestine)

62
Q

In most cases of GVHD T cell response develops against _____ histocompatibility antigens

A

In most cases of GVHD T cell response develops against Minor histocompatibility antigens

63
Q

Mature T cell effector mechanisms of GVHD: (3)

A
  • TNF
  • FasL
  • perforin-granzyme
64
Q

Symptoms of Acute GVHD:
• ________ cell death in skin, ____, GI tract vessels
• Rush, diarrhea, vomiting, GI tract _______

A

Symptoms of Acute GVHD
• Endothelial cell death in skin, liver, GI tract vessels
• Rush, diarrhea, vomiting, GI tract bleeding

65
Q

Drugs used in HSC transplantation:

Immunosuppression of the recipient is necessary because ____ is frequent (50-70%)

A

Drugs used in HSC transplantation:

Immunosuppression of the recipient is necessary because GVHD is frequent (50-70%)

66
Q

Drugs used in HSC transplantation: Donor T cell depletion. It is partial, because there is a need to retain a certain activity against the recipient for :

A

Drugs used in HSC transplantation: Donor T cell depletion. It is partial, because there is a need to retain a certain activity against the recipient for : GVL/GVT

67
Q

Induction of immune tolerance:

Inhibition of T cell activation by - 3 examples

A
  • Solubles MHC molecules
  • CTLA4-Ig
  • Anti-IL2R mAb
68
Q

Induction of immune tolerance:

Inhibition of Th1 cytokines - 3 examples

A
  • anti-TNF-α
  • anti-IL-2
  • anti-IFN-γ mAb
69
Q

Removal of T cells from the graft - How is it Preformed?

A

Magnetic Antibodies with Magnet collection allowing for Overall collection

70
Q

Which of the following is beneficial for the patient?
A. GVH
B. GVL/GVT
C. HVG

A

B. GVL/GVT

71
Q 
Which kind of rejection can be expected in case of
AB0 incompatibility
A. Hyperacute rejection
B. Acute humoral rejection
C. Acute cellular rejection
D. Chronic rejection
A

A. Hyperacute rejection

72
Q

Why the anti ABO antibodies are produced among
normal conditions?
A. Previous contact with foreign blood
B. Maternal antigen exposition
C. Carbohydrate antigens of intestinal microbiome
D. Exposition by plant pollens

A

C. Carbohydrate antigens of intestinal microbiome

GBA Immunology (15 decks)

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