Week 13 - Transplantation Immunology Flashcards
Transplantation Definition:
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.
Donor Definition:
The person who is giving the graft (cells, tissue or organ)
Recipient Definition:
the person who is receiving the graft
Graft Definition:
the transplanted cells, tissue or organ
Orthotopic Transplantation Definition:
The graft is placed to the original anatomic location
Heterotopic Transplantation Definition:
The graft is placed to another location (different from the original anatomic location)
Autotransplantation Definition:
The donor and the recipient is the same person.
Presumed consent (opting out) Strong version:
no need to get a permission of the relatives
Presumed consent (opting out) Weak version:
with the agreement of the relatives
Living will (opting in, contracting in): Involves -
Donor Card system
Place the Organs in order of the frequency of transplantation:
Liver, Heart, Kidney, Pancreas, Intestine, Lung
1) Kidney
2) Liver
3) Heart
4) Lung
5) Pancreas
6) Intestine
The ACTUAL most frequent transplantation is :
Transfusion
What is an Isograft (syn-graft)?
Graft donation between Monozygotic twins.
What is an allograft?
Graft donation between Non-Twins.
What is an autograft?
Graft donation - Host and Donor are the same Person.
What is a xenograft?
Graft donation - from non-human organism.
Primary and Secondary Rejection:
What is the difference?
Primary - 14 days till necrosis
Secondary - 6 days till Necrosis
Primary and Secondary Rejection:
What are the key players?
• CD4+ T cells : CD4+-CD8+ cooperation is also important.
Histocompatibility between donor and recipient:
MHC Reaction? By?
Strong and Rapid
• HLA-A
• HLA-B
• HLA-DR
Minor histocompatibility antigens ?
Reaction?
slower and milder
• H-Y (Y chromosome)
• HA-1～HA-5 non Y chromosome
Name 3 tissue specific antigens:
- ABO, Rh blood groups
- VEC (vascular endothelial cell) antigen system
- SK (Skjelbred ) antigen
Blood group antigens are also present on ______ _____ ________ ____ .
Blood group antigens are also present on blood vessel endothelial cells (as part of the donor tissue) !
Differences between organ and bone marrow stem cell
transplantation:
In Which one there is a cytoablation Needed?
bone marrow stem cell transplantation
Differences between organ and bone marrow stem cell
transplantation:
In Which one there is an Immune suppressive therapy is Needed?
organ transplantation
Differences between organ and bone marrow stem cell
transplantation:
In which one there is a HLA matching needed?
BOTH
Differences between organ and bone marrow stem cell
transplantation: Possible Major Complication of each?
Organ Transplantation Complication - Rejection
B.M Stem Cell Transplantation Complication - GVHD
Differences between organ and bone marrow stem cell
transplantation: Possible Success of each?
Organ Transplantation Success: acceptance
B.M Stem Cell Transplantation Success: tolerance
What is GVHD?
GVHD - Graft Versus Host: Proliferation of Anti-Host cells that attack the defenseless Host!
What is HVGD?
HVGD- Host Versus Graft: Proliferation of Anti-Graft cells that attack the Graft! (Rejection)
Transplantation of Islet of Langerhans: How?
Purified Islets Injected with Catheter to the Portal vein and Make the Liver Sinusoids their New Home!
“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?
Cornea Transplantation
e.g. glaucoma and cataracts
____ of T cells recognizing conventional antigens
recognize allogeneic MHC molecules.
1-10% of T cells recognizing conventional antigens
recognize allogeneic MHC molecules.
What are the cells that cause Alloreactivity Initiation in Rejection Process?
Host and Donor Dendritic Cells
Antigen Presentation to the Lymph Node residing T cells.
Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Allogeneic MHC State
Direct Recognition: Intact allogeneic MHC or in Peptide COMPLEX.
Indirect Recognition: Peptide of allogeneic MHC.
Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Cells presenting source - Donor/Recipient
Direct Recognition: DONOR CELLS (“D-D”).
Indirect Recognition: RECIPIENT CELLS.
Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Activated T cell
Direct Recognition: CD8+ and/or CD4+ T cells
Indirect Recognition: CD8+ and/or CD4+ T cells
Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Role in the rejection
Direct Recognition: Acute Rejection
Indirect Recognition: Chronic Rejection
Recognition of allogeneic MHC by recipient T cells, Direct Recognition Vs. Indirect Recognition:
Extent of Rejection
Direct Recognition: Intense (Acute Rejection)
Indirect Recognition: Mild (Chronic Rejection)
Types of host versus graft reaction (HVG): Timing of Each -Hyperacute, Acute, Chronic
- Hyperacute rejection: within minutes-hours
- Acute rejection (humoral or cellular): < 1month
- Chronic rejection: months - years
Hyperacute rejection, Mechanism by Antibodies for “
- ABO blood group antigens
- VEC (vascular endothelial cell) antigen
- HLA antigens
Origin of HLA sensitization - Try to Remember at Least 4 Examples
- Transfusion
- Pregnancy
- Previous transplantation
- Others (e.g. undetected spontaneous abortion, semeninduced antigen stimulation, cross-reactive microbes)
What is the main cause of Necrosis of the Graft in Hyperacute Rejection?
Thrombotic closure of graft vessel Ischemia.
What is the cause of the Thrombotic events in Hyperacute Rejection?
Complement System activation with Endothelial Damage.
Acute Rejection Types:
Humoral: vasculitis - Cause?
• Alloreactive IgG binds to the endothelial cells causing
endotheliitis.
Acute Rejection Types:
Cellular: parenchymal damage - Cause?
Direct allogeneic MHC/peptide complex recognition
• DTH (CD4+Th1)
• CD8+Tc mediated cell damage
Alterations of Chronic Rejection (3):
- Fibrosis
- Vascular sclerosis
- Decline in the graft function
Chronic Rejection: Mechanism
• Chronic inflammation with CD4+T cells and
macrophages
• Degenerative changes of the transplanted organs
due to non-immune factors
General approaches of prevention of transplantation rejection: Donor Selection Types (2)
• Live donor – relative: there is sufficient time for
genotyping
• Cadaver: transplantation list
General approaches of prevention of transplantation rejection: Ex vivo graft manipulation - How are
Immunocompetent cells being eliminated?
(At least 4 Examples)
- Steroid infusion of the graft prior to transplantation
- Tolerance induction
- Anti-CD28
- Anti MHC II
- Anti-CD4
General approaches of prevention of transplantation rejection: Possible helpful manipulation on Host
Immunosuppression
How to Glucocorticoids aid in Immunosuppression?
Competitive Transcription factors causing inhibition of Cytokine production (NFkB pathway Competitive)
4 examples for Immunosuppressants:
- CTLA4-Ig (Against B7-CD28 Interaction)
- Cyclosporine (Against Calcineurin)
- Rapamycin (Against mTOR)
- Anti-TCR
- Anti-IL-2R
Multiple Myeloma, AML, Amyloidosis, CML, Sickle cell Disease are all examples for diseases that are treated with ___ _______.
Multiple Myeloma, AML, Amyloidosis, CML, Sickle cell Disease are all examples for diseases that are treated with HSC transplantation.
Hematopoietic stem cell (bone marrow)
transplantation is used (among other uses) for ____________ of hematopoiesis after ______ ________therapy.
Hematopoietic stem cell (bone marrow)
transplantation is used (among other uses) for Reconstitution of hematopoiesis after chemo- and/or
radiotherapy.
Leukapheresis is used to obtain stem cells from _______ blood
Leukapheresis is used to obtain stem cells from peripheral blood
DLI: What is it for?
Donor lymphocyte infusion (DLI) – to treat relapse of Leukemia
MRD: What is it? Importance?
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!
Which of these is a description of a patient with HSC Donation: (Also point to monitor)
Mixed Chimera / Complete Chimera
Mixed Chimera
Monitoring of MRD is critical here - Leukemia Relapse!
Which of these is a description of a patient with DLI: (When is it given)
Mixed Chimera / Complete Chimera
Complete Chimera
Given after Mixed Chimera State - Prevention of Leukemia Relapse!
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
• Sufficient number of immunocompetent cells in the
graft
• Decline in immune defense in the recipient
• MHC differences between the host and the graft
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)
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)
In most cases of GVHD T cell response develops against _____ histocompatibility antigens
In most cases of GVHD T cell response develops against Minor histocompatibility antigens
Mature T cell effector mechanisms of GVHD: (3)
- TNF
- FasL
- perforin-granzyme
Symptoms of Acute GVHD:
• ________ cell death in skin, ____, GI tract vessels
• Rush, diarrhea, vomiting, GI tract _______
Symptoms of Acute GVHD
• Endothelial cell death in skin, liver, GI tract vessels
• Rush, diarrhea, vomiting, GI tract bleeding
Drugs used in HSC transplantation:
Immunosuppression of the recipient is necessary because ____ is frequent (50-70%)
Drugs used in HSC transplantation:
Immunosuppression of the recipient is necessary because GVHD is frequent (50-70%)
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 :
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
Induction of immune tolerance:
Inhibition of T cell activation by - 3 examples
- Solubles MHC molecules
- CTLA4-Ig
- Anti-IL2R mAb
Induction of immune tolerance:
Inhibition of Th1 cytokines - 3 examples
- anti-TNF-α
- anti-IL-2
- anti-IFN-γ mAb
Removal of T cells from the graft - How is it Preformed?
Magnetic Antibodies with Magnet collection allowing for Overall collection
Which of the following is beneficial for the patient?
A. GVH
B. GVL/GVT
C. HVG
B. GVL/GVT
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. Hyperacute rejection
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
C. Carbohydrate antigens of intestinal microbiome
