Term
| What type of transplantation involves taking skin grafts from the thighs of a burn victims to put on that same person's arms? |
|
Definition
|
|
Term
| What type of transplantation involves taking skin grafts from one identical twin to use on another? |
|
Definition
|
|
Term
| What type of transplantation involves a child receiving a kidney from their cousin? |
|
Definition
|
|
Term
| What type of transplantation involves getting a porcein valve replacement? |
|
Definition
|
|
Term
| True or False: Someone with an AO genotype is compatible with an AB recipient group |
|
Definition
True.
Remember, A is dominant (AB can be co-dominant), and someone with AB genotype lacks antibodies to either A or B antigens (Universal recipient!)
In contract, an AB donor could not be received by an AO recipient, because the AO recipient has anti-B antibodies. |
|
|
Term
| How does agglutination occur in transfusion rejection? |
|
Definition
Antibodies against donor blood group antigens bind to vascular epithelia of graft, initiating an inflammatory response that occludes vessels.
Grafts can become engorged and purple because of hemorrhage.
Think about someone with an OO genotype. They can only receive blood from someone else who is OO. |
|
|
Term
True or False.
Transplantation of ABO incompatible organs will subject the graft to chronic, fibroblast-mediated rejection |
|
Definition
False!
Hyper-acute, Type II/III Ab-mediated rejection will most likely occur. |
|
|
Term
| Which minor blood group antigen is of importance because of its high immunogenicity? |
|
Definition
RhD antigen (only on RBCs).
Universal blood donors are O RhD-
Universal recipients are AB RHD+ |
|
|
Term
| What is Erythroblastosis Fetalis? |
|
Definition
This is a unique complication associated with RhD antigen.
If RhD- mother carries an RhD+ child, she will generate bodies against RhD. Therefore, if she carries a second, RhD- child, those anti-RhD IgG antibodies will cross the placenta and attack the fetus, causing severe hemolysis. |
|
|
Term
| What are 5 reactions associated with transfusion rejection? |
|
Definition
SHORT
Hemolysis
HLA/alloantiibodies
Allergy
Anti-WBC antibodies
Immunocompromised and recipient WBC attack.
1) Acute hemolytic reaction due to incompatible RBCs
2) Febrile non-hemolytic transfusion reaction caused by alloantibodies reacting to HLA antigens.
3) Allergic nonhemolytic reactino due to preservatives or plasma proteins.
4) Transfusion related acute lung injury by anti-WBC antibodies
5) Transfusion associated graft versus host diseases caused by transfusion into immunosuppressed patients and engraftment of donor WBCs |
|
|
Term
| What are 3 methods of preventing transfusion-associated reactions |
|
Definition
1) Blood compatibility (prevents hemolysis because of incompatible RBCs)
2) Washing RBCs prior to transfusion (prevents HLA issues, allergic issues and WBC antibody issues
3) Transferring "leukopoor" and irradiated PPRBCs (prevents WBC attack of immunocompromised individuals) |
|
|
Term
Will a grafts from inbred parental strain be rejected by an F1 hybrid?
What abut a graft from the F1 hybrid into the inbred parental strain |
|
Definition
1) No, the F1 hybrid has the parental HLA (co-dominant expression)
2) Yes, the parental strain only has 1 of the HLA genotypes, while the F1 generation is co-dominant. The lacking genotype will initiate an immune response. |
|
|
Term
| What gives rise to minor H antigen differences and what are their consequences? |
|
Definition
Polymorphic self proteins that differ in amino acid sequence between individuals create minor differences between donor and recipient.
Grafts that share the same MHC may still be rejected over time. |
|
|
Term
|
Definition
Serological testing called a "lymphocytotoxicity assay"
Basically use "sera" that contain known anti-HLA antibodies to detect the presence of HLA antigens in a sample.
Antigens that are recognized will be fixed by complement and lysed (dye enters)
HLA matching improves allograft survival in both solid organ and bone marrow transplantation (both involve MHC expression, while RBCs do not express MHC)!
This works for solid organ transplantation, but does not involve DNA analysis of HLA-alleles expressed in cells, which is required for bone marrow transplant. |
|
|
Term
| How is solid organ and bone marrow transplant HLA-typing different? |
|
Definition
| Both involve HLA matching, but the resolution of DNA analysis of expressed HLA-alleles is required for bone marrow transplant. |
|
|
Term
| Why do corneal and liver allografts not require HLA-typing? |
|
Definition
| These allografts are to pro-tolerant, immune privileged locations |
|
|
Term
| How is the immune status of a transplant recipient determined? |
|
Definition
Pre-formed antibodies to HLA antigens are evaluated by using serum of recipient against a panel of HLA-antigens using cells or ELISA.
You match Ab-antigen interactions of the donor with the recipient.
The percent of antigens the antibodies react to are estimated as the Panel Reactive Antibody (PRA). The bigger the PRA, the worse the chances of matching.
PRA IS NOT ORGAN SPECIFIC
You are looking for complement fixation and cell damage in cross-match testing |
|
|
Term
| What are you looking for in "cross-match" testing and how do you interpret your results? |
|
Definition
You take organ donor cells and expose them to recipient serum
You are looking for complement fixation and cell damage in cross-match testing. A (+) cross-match means NO GO. |
|
|
Term
| What features of an adaptive immune response does an immune response to transplanted organs show? |
|
Definition
1) Memory and specificity of rejection (prior exposure leads to accelerate rejection)
2) Lymphocyte-mediated process (lymphocytes from a sensitized individual can transfer reactivity to a naive individual)
3) T-cell mediated (deplete T cells and you reduce reaction) |
|
|
Term
| What is the difference between the direct and indirect pathways of allorecognition and rejection? |
|
Definition
Both processes occur in secondary lymphoid tissues (LN and spleen)
1) Indirect- MHC-derived peptides from donor are digested by host APCs and presented to host T-cells (chronic rejection)
2) Direct- is unique to transplantation and involves recognition of donor MHC directly without peptide presentation (acute rejection). The direct pathway can be peptide-dependent or peptide-independent. |
|
|
Term
| Explain the effector mechanisms of graft rejection. |
|
Definition
Analogous to type II, III and IV hypersensitivity reactions.
1) Antibodies produced by B cells target endothelial cells and mediate rejection by either complement mediated cell death or by forming immune complexes that recruit inflammatory cells.
2) CD4 T cells and CD8 T cells secrete cytokines that activate macrophages, release cytolytic molecules and cause rejection in a DTH like reaction. |
|
|
Term
| What kind of rejection occurs when a recipient has pre-existing antibodies to ABO antigens or HLA antigens that respond within minutes to hours by type II and II hypersensitivity reactions? |
|
Definition
Hyperacute
These cannot be treated an only prevented by testing for ABO compatibility, crossmatching and pre-transplant interventions to remove pre-existing antibodies. |
|
|
Term
| What type of rejection occurs when T-cells become sensitized to alloantigens (HLA antigens) (Type IV hypersensitivity reaction) and B cells that produce alloantibodies (Type III) within days to weeks of transplantation ? |
|
Definition
Acute
You can treat with immunosuppression, steroids, T-cell depletion and plasmapheresis (Ab removal) |
|
|
Term
| Why can you not treat chronic rejection? |
|
Definition
Fibroblast-mediated fibrosis and tissue damage.
You want to optimize immunosuppression to reduce toxicity and preserve existing graft function. |
|
|
Term
| What are the 4 types of hypersensitivity immune reactions? |
|
Definition
1) Allergic (IgE)
2) Cytotoxic/Ab-dependent (IgG and IgM-complement)
3) Immune Complex (IgG- complement)
4) Delayed-type (Ab-independent/Cell-mediated)- T cells |
|
|
Term
| What anti-cytokine antibody might you give to prevent inflammatory bowel disease? |
|
Definition
| anti IL-12/23 (intracellular immunity and extracellular immunity). |
|
|
Term
| How are stem cells obtained for autologous and allogenic bone marrow transplants? |
|
Definition
CD34+ cells are taken from peripheral blood, marrow or cord blood to treat malignancy or immunodeficiency.
In the Autologous case, they are taken from the patient and then re-infused after chemotherapy and radiation for immunosuppression
In the Allogenic case, they are taken from a donor and infused into a patient after the same treatment. |
|
|
Term
| Why is HLA type but not ABO matching considered for bone marrow transplants? |
|
Definition
Expression of AB antigens on stem cells is low and no issues with engraftment are seen.
However, if the stem cells become RBCs that are incompatible, they can lead to hemolytic anemia. |
|
|
Term
| What are the primary targets of Graft versus host disease? |
|
Definition
| When donor T cells attack recipient tissues after allogeneic bone marrow transplants, these reactions target skin, liver, gut and oral mucosae. |
|
|
Term
| Why do porcein xenografts cause hyperacute rejection? |
|
Definition
Antibodies and Complement!
Humans have antibodies against pig endothelial carbohydrates and pig cells are attacks by human complements
To avoid this issue, you use Decay Activating Factor which prevents complement activation. |
|
|
Term
| How do Cyclosporine and FK506 (Tacrolimus) achieve immunosuppression |
|
Definition
Inhibit Calcineurin, which prevents Ca-mediated up-regulation of NFA, thereby BLOCKING CYTOKINE PRODUCTION.
In cases of nephrotoxicity, you should use Serolimus and Everolimus (rapamycin) instead, with Mycophenolate Mofetil. |
|
|
Term
| How does Mycophenolate Mofetil achieve immunosuppression? |
|
Definition
| Blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis in lymphocytes. |
|
|
Term
| How does Rapamycin (Serolimus) act in immunosuppression? |
|
Definition
| Block IL-2 signaling (inhibit T-cell proliferation). |
|
|
Term
| Why would you treat a kidney transplant patient with corticosteroids? |
|
Definition
To reduce inflammation by inhibiting macrophage cytokine secretion.
Remember, these drugs inhibit cyclooxygenase (can't make prostaglandins) and lipoxyganse (can't make leukotrienes or lipoxides). |
|
|
Term
| How do Anti-CD3 monoclonal antibodies act to suppress the immune system? When would you use this? |
|
Definition
Depletes T cells by binding CD3 and promoting phagocytosis or complement-mediated lysis
Remember, CD3 is the portion of the TCR complex that is responsible for intracellular signaling (TCR a and b are for binding)
Used to treat acute rejection. |
|
|
Term
How do anti-IL-2 receptor antibodies act in immunosuppresion?
What about CTLA4-Ig? |
|
Definition
They block IL-2 binding and T-cell proliferation.
May also opsonize and help eliminate activated IL-2R-expressing T cells
2) CTLA4-Ig is a negative T-cell regulator that binds CD28 on T-cells and blocks costimulation from B7 (it induces tolerance) |
|
|
Term
| What would anti-CD40 antibodies do? |
|
Definition
| They block CD40 (macrophage): CD40L (T-cell) binding and inhibit macrophage and endothelial activation. IMMUNOSUPPRESSION. |
|
|
Term
| Explain the "Induction" and "Maintenance" phases of immunosuppression. |
|
Definition
1) Induction-
peri-operatively and immediately after transplant, making use of protein/antibody-based cell depleting agents like thymoglobulin, alemitizumab (these increase risk of infection) and non-depleting agents such as anti-CD25 antibodies liek basiliximab and daclizumab
2) Maintenance (for life)
Calcineurin inhibitors (tacrolimus/FK506 and cyclosporine) in combination with mycophenolate mofetil (Gaunine synthesis in T-cells).
Avoid steroids if possible and use mTOR inhibitors (Siralimus and Everolimus/Rapamycin) in the setting of nephrotoxicity or skin cancers where mTOR inhibitors could have beneficial anti-tumor effects. |
|
|
Term
| Which drugs would you use to treat acute rejection and why? |
|
Definition
1) Mild steroids
2) Cell-depleting agents (Thyroglobulin) if steroids don't work)
3) If antibody- or complement-mediated rejection is detected, use Plasmapheresis (remove antiboies), Intravenous immunoblobulin (dampen antibody production and effects) and Ritximab (deplete B cells that don't respond to other treatments). |
|
|
Term
| If antibody- or complement-mediated acute rejection is detected, what should you treat with? |
|
Definition
1) Plasmapheresis (remove antiboies)
2) Intravenous immunoblobulin (dampen antibody production and effects)
3) Ritximab (deplete B cells that don't respond to other treatments). |
|
|
Term
| How do you treat chronic transplant rejection? |
|
Definition
| Adjust immunosuppressive routine to avoid nephrotoxicity effects of calcineurin drugs by switching to sirolimus and adding mycophenolate if not already added. |
|
|
Term
| What are "immuneprivilege" sites in transplantation? |
|
Definition
Theese sites are resistant to rejection from allogeneic transplants
They include the eyes, brain, testis, uterus and hamster cheek pouch.
They modulate immune responsiveness with TGFB and IDO (leeds to Treg production), IL-10 and FAS-ligand. |
|
|
Term
| How do "immune-privileged" sites avoid the need for HLA or ABO matching? |
|
Definition
| They modulate immune responsiveness with TGFB and IDO (leeds to Treg production), IL-10 and FAS-ligand. |
|
|
Term
| What is the mechanism of tolerance between non-identical twins that share a single placenta during pregnancy? |
|
Definition
| Central tolerance arising from persistent chimerism of the twins' cells with one another. |
|
|
Term
How does "cytokine deviation" relate to self-tolerance in transplantation?
What drugs will do this? |
|
Definition
Differentiation of Th2 cells limits the producing of inflammatory cytokines
Cyclosporine and Rapamycin |
|
|
Term
| Where does antigen segregation (physical barrier to self-antigen access to lymphoid system) occur? |
|
Definition
| In peripheral organs (thyroid and pancreas) |
|
|
Term
| Why do neonatal heart transplants not require ABO matching? |
|
Definition
| Before food/bacterial exposure, antibodies have not yet developed. No complement fixation or hemolysis will occur. |
|
|
Term
| WHy does anti-A and anti-B antibody transmission not cause a similar situation to Erythroblastosis Fetalis? |
|
Definition
These antibodies are of the IgM type, and do NOT cross the placenta.
anti-RhD antibodies (against protein) are IgG type and they DO pass through the placenta |
|
|
Term
|
Definition
| This is a test of agglutination during an initial pregnancy to check for an RhD+ child in an RhD- mother (prevent Erythroblastosis Fetalis in second pregnancy). |
|
|
Term
| Which HLA molecules are most polymorphic, and therefore most important for predicting rejection? |
|
Definition
DRB (MCH-II) and HLA-A HLA-B (MHC-I)
Polymorphism and Polygeney leads to multiple MHC forms which could be recognized as foreign by donor. |
|
|
Term
| What is the general sequence of trials to evaluate the immune status of a transplant patient? |
|
Definition
1) PRA score determination with a panel of HLA-antibodies against the recipients serum
2) Crossmatch testing using a recipient's serum against a donor's cells. |
|
|
Term
| How can MHC-identical grafts still undergo rejection? |
|
Definition
Minor histocompatibility antigens!
Polymorphic forms of self proteins that create antigen differences. |
|
|
Term
| Would you expect a difference in rejection type between MHC-1 and MHC-II class mismatches? |
|
Definition
Yes
MHC-I is expressed by all cells and would lead to a hyperacute reaction (Type II/III Ab-mediated)
MHC-II does not lead to hyperacute, but still rejection (only expressed on macrophages, B cells and DCs) |
|
|
Term
True or False
Graft vs. Host Disease (GVHD) occurs only in bone marrow transplant and kidney transplant surgery? |
|
Definition
False!
GVHD is specific for bone marrow transplant.
In kidney transplant, HOST cells attack graft antigens. |
|
|
Term
| Which immunosuppression regimens would be used to induce effects of Central Tolerance and Clonal Deletion |
|
Definition
| Alemituamib and Thyroglobin, as well as Rituximab (T/B cell deletion) |
|
|
Term
| Which immunosuppression regimens would be used to induce Peripheral Anergy? |
|
Definition
| CTLA-4 Ig, Anti-CD40L and Cyclosporine would prevent co-stimulation, leading to anergy. |
|
|
