allograft
-transplant of an organ or tissue from one individual to another of the same species with a different genotype
xenograft
-transplant between individuals of different species
d
What is the leading cause of Death With a Functioning Graft (DFWG)?
a) diabetes
b) hypertension
c) cancer
d) CVD
infection; rejection
_______ and ________ are two major barrier to successful organ transplantation.
a
Which HLA matching system is most used?
a) 6 match
b) 10 match
c) 4 match
d) 3 mathc
Hematopoietic stem cell transplantation (HSCT)
-is used to treat patients with hematological malignancies, such as non-Hodgkin’s lymphoma and to reconstitute hematopoiesis following high-dose chemotherapy.
to repopulate the bone marrow niche with a complete lineage of hematopoietic stem cells
What is the ultimate goal of Hematopoietic Stem Cell Transplantation (HSCT)?
gradually removing patient's immune system using high-dose radiotherapy and immunosuppressive drugs after HSC have been harvested
What is Myeloablative conditioning?
CD34
-cell surface protein found on stem cells that functions as an adhesion molecule to keep stem cells attached to bone marrow
antagonist of CXCR4 receptor; blocks binding of SDF1a; allows for mobilization of CD34 cells into peripheral blood
Plerixafor MOA?
G-CSF; non-hodgkin's lymphoma; multiple myeloma
Plerixafor is used in combination with ________ to mobilize hematopoietic stem cells for transplantation in patients with ______ &________.
a
Which cytokine is responsible for activating T-cells?
a) IL-2
b) IL-4
c) IL-10
d) all of the above.
hyperacute rejection
-Occurs within minutes to days of transplantation, is due to preformed IgG antibodies in the recipient that react against antigens in the transplanted organ
acute rejection
-occurs most frequently in the first 6 months after transplantation when immune cells infiltrate the allograft and cause tissue destruction.
chronic rejection
-allograft function slowly deteriorates and there is histologic evidence of fibrosis, progressive hypertrophy, and eventual failure of organ transplant.
a
Which form of rejection is a "B-Cell issue"?
a) hyperacute
b) acute
c) chronic
d) both a & b
b
Which form of rejection is a mainly mediated by T-cells?
a) hyperacute
b) acute
c) chronic
d) both a & b
a
Which form of treatment is best to treat Acute rejection?
a) immunosuppressive induction
b) immunosuppressive maintenance
b
Which form of treatment is best to treat Chronic rejection?
a) immunosuppressive induction
b) immunosuppressive maintenance
induction therapy
-the goal of this therapy type is to greatly reduce the immune system for 2 weeks post-transplant to reduce hyperacute and acute rejection.
maintenance therapy.
-the goal of this therapy is to reduce the immune system's ability to recognize and reject the foreign organ or tissue, while limiting toxicity.
b
Which therapy is tailored to the individual patient to provide lifelong suppression of the immune system?
a) immunosuppressive induction
b) immunosuppressive maintenance
chronic allograft nephropathy (CAN)
-the most common underlying long-term cause of allograft loss.
non-adherence
_________ occurs in 50% of renal transplant patients and is responsible for approximately 35% of graft patients.
t cell gets activated by MHC class II and B7 co stimulation complex; activates calcineurin which leads to production of IL-2
Explain the T-cell activation cycle.
autocrine; m-TOR and cyclin-dependent kinase
_______ stimulation of IL-2 results in cell proliferation by a pathway involving ________.
t-cell depleting agents, IL-2 receptor blockers
What are our classes of Induction agents (2)?
thymoglobulin
-purified IgG –based polyclonals obtained by immunization of rabbits with human thymocytes (T-cells).
-most common induction agent used in the United States.
cyclosporine; corticosteroids
Basiliximab is used in conjunction with _______ and _________.
Basiliximab; thymoglobulin
_________ is not as an effective immunosuppressant but is less toxic than _______.
Basiliximab
-IL-2 receptor antagonist
a
________ is most commonly used in patients at low risk for acute rejection.
a) Basiliximab
b) Thymoglobulin
c) Calcinuerin inhibitors
d) Everolimus
e) Sirolimus
e
The combined used of CNIs and ______ should be avoided because of risk of nephrotoxicity in early post-transplant period.
a) Basiliximab
b) Thymoglobulin
c) Calcinuerin inhibitors
d) Everolimus
e) Sirolimus
d,e
Which immunosuppressants have a narrow Therapeutic Index?
a) Basiliximab
b) Thymoglobulin
c) Calcinuerin inhibitors
d) Everolimus
e) Sirolimus
f) Belatacept
Everolimus, sirolimus
_______ has improved solubility, greater bioavailability, and shorter half life than ________.
irreversible nephrotoxicity, cardiovascular events, infection, cancer
Long-term use of Calcinuerin inhibitors (CNI) can cause what? (5)
Calcinuerin inhibitors
-suppress the immune system by preventing IL-2 production in T-cells
live vaccines; sunlight
Tacrolimus is contraindicated with ________ and patients should avoid ________.
false
Tacrolimus extended-release tablets are safe to be substituted for capsules and granules. T/F?
prodrug that gets converted into mycophenolic acid and acts as a cytostatic agent by preventing proliferation of t-cells via purine synthesis
Mycophenolate mofitil MOA?
f
Which immunosuppressant is a decoy receptor that interferes with APC CD 80/86 interactions?
a) Basiliximab
b) Thymoglobulin
c) Calcinuerin inhibitors
d) Everolimus
e) Sirolimus
f) Belatacept
f
Which medication can cause Post-transplant lymphoproliferative disorder in the CNS?
a) Basiliximab
b) Thymoglobulin
c) Calcinuerin inhibitors
d) Everolimus
e) Sirolimus
f) Belatacept
Epstein-barr virus
Patients without immunity to _________ can not take Belatacept.
reactive oxygen species
Subsequent warm re-perfusion of grafts causes _______ to be produced which further promote cell damage.
delayed graft function
-the need for dialysis within one week after renal transplantation caused by ischemia/re-perfusion injury
ruthenium & boron carbonyl
What are the prodrugs of Carbon Monoxide that can prevent Ischemia/re-perfusion injuries and graft rejection?