Final - Transplant Flashcards
Immunology behind immunosuppression:
_____ mediated rejection = infiltration of the allograft by lymphocytes and other inflammatory cells
T cell mediated (cellular response)
Immunology behind immunosuppression:
_____ mediated rejection = circulating donor-specific antibodies/immunological evidence of an antibody mediated destruction
B cell (antibody) rejection (humoral response)
T cell activation requires __#__ signals
3 signals
T cell activation steps: #1. The T cell receptor (\_\_\_\_) interacts with \_\_\_\_\_\_\_
CD3 interacts with APC (antigen presenting cells)
T cell activation steps: #2. The co-stimulatory signal of \_\_\_\_\_\_ on the surface of APCs interacting with \_\_\_\_\_\_ on T cells
CD80/86 on APCs interacts with CD28 on T cells
T cell activation steps: #3. \_\_\_\_ binds to CD25 (which activates the mammalian target of \_\_\_\_\_\_) and subsequent proliferation and activation of the T-Cell
IL-2 binds to CD35;
target of rapamycin pathway
Rejection Timeline:
Hyperacute rejection – happens minutes to hours after transplant
& is mediated by ___________
preformed circulating antibodies
Rejection Timeline:
Acute rejection – occurs within days - months after transplant
& is mediated by _______
by host T-lymphocytes
Rejection Timeline:
Chronic rejection – happes over months to years after transplant
& is mediated by _________
& will see progressive decline in organ function….
mediated by BOTH cell mediated and humoral processes
Pre-Transplant Immunologic Evaluation:
what 4 things should be looked at?
ABO blood group determination
MHC
Determination of PRA (panel reactive antibodies)
Determination of Cross-Match
3 different types of immunosuppressive strategies
- induction therapy
- maintenance therapy
- rescue therapy
Patients who are at higher risk of rejection?
- Depends on the organ (intestines are the highest risk)
- Race: African Americans are at highest risk
- If poor PRA result
- Age: if younger = higher rejection risk
Induction Regimens consist of what?
Steroids + (Depleting agent or Non-Depleting Agent)
examples of Depleting agents?
Thymoglobulin
Atgam
Alemtuzumab
example of non-depleting agent?
basilximab
Thymoglobulin comes from what animal?
Atgam comes from what animal?
thymp: rabbit
Atgam: horse
The Antithymocyte globulins (Thymo and Atgam) are animal derived _____ antibodies directed against multiple _________
IgG antibodies;
multiple T cell specific antigens (aka polyclonal)
Antithymocyte globulins:
when the antibody and antigen bind:
it results in what things?
- opsonization (marking something for phagocyte to come get)
- T cell lysis
- rapid/profound lymphopenia
aka depleting allll lymphocytes in the body
What Immunosuppression strategy is it?
intense prophylactic therapy at the time of transplantation
induction
What Immunosuppression strategy is it?
chronic immunosuppression
Maintenace
What Immunosuppression strategy is it?
intense therapy utilized in response to a rejection episode
rescue
Antithymocyte globulins
which one is often capped at 150 mg/dose
Thymoglobulin
Antithymocyte globulins
which one is dosed as 10 - 15 mg/kg/day
atgam
Antithymocyte globulins
which one is dosed as 1-1.5 mg/kg/day for 4 - 7 days
Thymoglobulin
Antithymocyte globulins
ADEs?
- Myelosuppression (leukopenia/thrombocytopenia)
- cytokine release syndrome
- serum sickness
- infections
- lymphoproliferative disease
Antithymocyte globulins: ADEs
Has dose limiting myelosuppression — monitor what two things?
WBC and Platelets
Antithymocyte globulins: ADEs
Reduce dose by 50% when?
if WBC are 2000 - 3000 cells/mm3
OR
Platelet count is 50,000 - 75,000 cells/mm3
Antithymocyte globulins: ADEs
consider discontinuation when?
if WBC < 2000 cells/mm3
OR
Platelet count < 50,000 cells/mm3
Antithymocyte globulins: ADEs
sxs of cytokine release syndrome?
fever/chills
tachycardia
hypotension
Antithymocyte globulins: ADEs
how to prevent cytokine release syndrome?
pre-medicate: Steroids, diphenhydramine, APAP
also hella frequent vital sign monitoring :Q15 min for 1st hour then hourly
Antithymocyte globulins: ADEs
sxs of serum sickness?
arthralgias
myalgias
headaches
Antithymocyte globulins: ADEs
treat serum sickness how?
tx with corticosteroids
happens as a hypersensitivity reaction — thus do not retry any of the globulins
Antithymocyte globulins: ADEs
serum sickness happens when in relation to the dose?
it is a delayed rxn = can be up to 2 weeks post dose
Antithymocyte globulins: Administration
infused over _____ hours
______ line preferred
over 6 - 8 hours
central line
(can do peripheral — just add heparin/hydrocortisone to prevent phlebitis)
Antithymocyte globulins: How to manage infusion related rxns?
slow down the infusion by 50%
antihistamines/methylpred/epinephrine should be available
Alemtuzumab:
Is a _________ monoclonal antibody
humanized; ANTI-CD52