Micro- Infections in Recipients of Solid Organ Transplantation Flashcards
What is presensitization for SOT?
when the transplant recipient has a high number of preformed circulating anti-HLA antibodies leading to increased risk of rejection of the transplanted organ
What do antiproliferative agents used for immunosuppression do?
Which drugs are anti-proliferatives?
Anti-proliferative drugs inhibit purine synthesis which limits B and T cell division and proliferation blunting CELL-MEDIATED immunity
- azathioprine
- Mycophenolate Mofetil [MMF]
What is the mechanism of action of MMF?
What 2 infections does it put patients at an increased risk for?
It is inosine monophosphate dehydrogenase inhibitor which disrupts de novo purine synthesis
[disrupts guanine synthesis]
It puts patients at increased risk for:
- BK nephropathy
- CMV
How do corticosteroids cause immunosuppression?
They block T-cell and APC cytokine expression:
- impairing T-cell activation/proliferation [IL-2]
- inhibiting inflammatory response [IL-1]
What is the ultimate result of using corticosteroids?
- lymphocytopenia, monocytopenia, neutrophilia
2. antibody suppression only occurs at high doses for long periods of time
What is the MOA of polyclonal anti-lymphocyte antibodies?
Opsonize leukocytes and platelets and elicit immune suppression via T-cell inactivation
For how long does lymphopenia last after giving a patient polyclonal anti-lymphocyte antibodies?
What syndrome can be caused by this?
What infections are patients at an increased risk for?
lymphopenia lasts for a year and has increased infection risk for over 3 months after administration.
Cytokine release syndrome due to ativation of T-cell before it is destroyed:
fever, chills, pulm edema, aseptic meningitis
Increased risk of:
- viral infection
- lymphoid malignancy
What are the 2 main polyclonal anti-lymphocyte antibodies?
- ATG [anti-thymocyte globulin] = rabbit
2. ATGAM [anti-human thymocyte globulin] = equine
What are the 5 monoclonal antibodies used in host immunosuppression?
What specifically do they each attack?
- OKT3 = anti-CD3
- Basiliximab, Daclizumab = anti CD25
- Alemtuzumab = anti CD52
- belatacept = CTLA4-Ig complex that binds to APCs
- rituximab = anti CD20
What is the MOA of OKT3?
What is the major side effect?
It is anti-CD3 and depresses T-cells via TCR transduction blockade
[Does not allow activation of T-cells]
SIDE EFFECT = cytokine release syndrome
What is MOA of basiliximab, daclizumab?
They are anti CD-25 so they block IL-2R inhibiting clonal proliferation and differentiation of activated T cells.
- no cytokine storm
What is the MOA of alemtuzumab? What is the major side effect?
It is anti-CD52, so it binds T, B, NK, monocytes and macrophages that have CD52.
This leads to Ab-dependent, cell-mediated lysis.
Side effect: neutropenia
What is the MOA of rituximab?
What is it specifically used for?
It is anti-CD20 and targets B cell lymphocytes.
It is used to reduce presensitization
What is the MOA of calcineurin inhibitors?
What are the 2?
Block calcineurin and inhibit T-cell activation and IL-2 production
- Cyclosporine
- isolated from tolypocladium - tacrolimus
- isolated from streptomyces
What is the MOA of mTOR inhibitors?
How do they compare to calcineurin inhibitors?
What is the main example?
What 2 side effects?
They inhibit mTOR thus blocking G0 to G1 transition and G1-S phase of T-cell activation.
They are more selective than CIs.
Sirolimus
Side effects: delayed wound healing, oral ulcers
What 4 factors affect risk of infection in SOT?
- time period after transplant
- type of transplant
- pre-transplant exposure
- donor-derived infections
What factors contribute to a patients “net state of immunosuppression”?
- type, dose, timing of immunosuppressive meds
- Immunomodulatory viruses:
- CMV, EBV, HIV, HBV, HCV - diabetes or renal insufficiency
What epidemiologic exposures affect a patients risk of infection post-transplant?
- nosocomial vs. CA
- exposure pre and post transplant
- prophylaxis
What is given as prophylaxis if the patient has:
- CMV
- PCP
- Fungal infection
- TB
- ganciclovir/valganciclovir
- TMP- SMX or [dapsone, atovaquone, inhaled pentamide]
- nystatin, fluconazole, ampho B
- pyridoxine, isoniazid
What are the 3 most common infections that occur in the first month after SOT?
- Nosocomial infections predominate
- ventilator pneumo, CVC bacteremia, UTIs - Bacterial & Candida from surgical technique and post-op care
- donor-derived infection
What time period after SOT has the highest net state of immunosuppression?
1-6 months
What infections are most common in the intermediate post-transplant stage [1-6 months]?
- viral reactivation - CMV, EBV, HBV, HCV
- opportunistic infections
- aspergillus
- Cryptococcus
- nocardia
- listeria
- t. gondii
What causes reactivation of CMV during intermediate posttransplant stage?
discontinuation of gangiclovir prophylaxis
What type of infection predominates the late post-transplant stage [over 6 months]?
community-acquired infections because not the patient is at home with a good allograft and minimal suppression.
- Viral respiratory infections: Flu, parainfluenza, RSV, adenovirus, human metapneumovirus
- bacterial respiratory infections: legionella, pneumococcus
