Finals-Overview In Organ Transplantation Flashcards
Developed surgical technique of the vascular anastomosis
Alexis Carrel
he was the first to report a series of human-to-human kidney transplants in the 1940s
Yu Yu Voronoy
He learned that immune system plays a crucial role in the failure of skin grafts; birth of transplant immunobiology
Sir Peter B. Medawar
He performed the first human transplant with long-term success in kidney transplant between identical twins and no immunosuppression
was required
Joseph Murray
the first liver transplant was performed by
Thomas Starzl
the first lung transplant was performed by
James Hardy
first pancreas transplant was performed by
William Kelly and Richard Lillehei
first successful heart transplant was performed by
Christiaan Barnard
is the process of transferring an organ, tissue, or cell from one place to another
Transplantation
surgical procedure wherein a
failing organ is being replaced by a functioning organ
Organ Transplantation
Organ transplant in the same anatomic location in the recipient as it was in the donor
Orthotopically
Organ transplant in another anatomic location
Heterotopically
Tranplatation from one part of the body to another part in the same person (skin, vessels, bone, cartilage,
nerve).
no immunosuppression is required
Autotransplant
from one person to another of the same species; except identical twins;immunosuppression is
required to avoid rejection of the donated organ
Allotransplant
Transplant from one organism to another of a different species;
animal-to-human transplant
Xenotransplant
Antigen encoding genes are located on chromosome
6
Class of antigens that are expressed by all nucleated cells
Class I
##FOOTNOTE
HLA-A, HLA-B, HLA-C
Class of antigens that are expressed by antigen- presenting cells (APCs) such as B lymphocytes, dendritic cells, macrophages, and other phagocytic cells.
Class II
HLA-DR, HLA-DP, HLA-DQ
HLA can trigger rejection via two mechanisms. This mechanism is the most common mechanism in which the damage is caused by activated T-lymphocytes
Cellular rejection
This mechanim of rejection by the HLA is mediated by circulating antibodies against the donor’s HLA molecules
Humoral rejection
The process of one’s body discrminating the immune system of each persons between self and nonself cells and tissues
Allorecognition
Tcells play a crucial roll
True or False
Indirect recognition occurs when the recipient’s T cells are activated by direct interaction with the donor’s HLA molecules.
False
this is direct recognition
True or False
Indirect recognition occurs when the recipient’s T cells are activated by interaction with APCs that have processed and presented the foreign antigen.
TRUE
Rejection is divided into three main types. These are
Hyperacute, acute and chronic
a very rapid type of rejection, results in irreversible damage and graft loss within minutes to hours after organ reperfusion
Hyperacute
It is triggered by preformed antibodies against the donor’s HLA or ABO blood group antigens.
These antibodies activate a series of events that result in diffuse intra- vascular coagulation, causing ischemic necrosis of the graft.
the most common type of rejection, usually occurs within a few days or weeks posttransplant
Acute Rejection
it is further divided into cellular (T-cell–mediated) rejection, humoral (antibody-mediated) rejection, or a combination of both.
The diagnosis is based on the results of biopsies of the transplanted organ, special immu- nologic stains, and laboratory tests
This type of rejection occurs slowly and usually is progressive. It can manifest within the first year posttransplant but most often takes place gradually over several years
Chronic rejection
As advances in immunosuppression have diminished the incidence of acute rejection, this form of rejection is becoming more common.
Immunosuppresion is delivered in two phases namely
Induction and maintenance
Immunosuppression phase starting immediately posttransplant, when the risk of rejection is highest
Induction
Immunosuppression phase usually starting within days posttransplant and usually continuing for the life of the graft and the recipient
Maintenance
During which time period is the degree of immunosuppression highest post-transplant, requiring prophylaxis against opportunistic pathogens?
First 3 to 6 months
during this time, prophylaxis against a number of different bacterial, viral, or even antifungal opportunistic pathogens is administered.
Immunosuppressive phase which includes the use of depleting or nondepleting antibodies within the first month posttransplant
Induction
induction with antibody regimens may prevent acute rejection, potentially leading to improved graft survival and the use of less maintenance immunosuppression.
A depleting antibody that is a purified gamma globulin obtained by immunizing rabbits with human thymocytes.
Thymoglobulin (Rabbit antithymocyte globulin)
The only available anti-CD25 monoclonal nondepleting antibody; not designed to be used to treat acute rejection. Its selectivity in blocking IL-2–mediated responses makes it a powerful induction agent without the added risks of infections, malignancies, or other major side effects.
Basiliximab
## FOOTNOTE
it is followed by the use of calcineurin inhibitors, corticosteroids, and MMF as maintenance immunosuppression.
An anti-CD52 monoclonal antibody initally used to treat chronic lymphocytic leukemia; its use has grown in the field of transplantation, given its profound lymphocyte-depleting effects.
Alemtuzumab
causes cell death by complement-mediated cytolysis, antibody-mediated cytotoxicity, and apoptosis. One dose alone (30 mg) depletes 99% of lymphocytes.
MOA:
Binds to cyclophilin
Inhibits calcineurin and IL-2 synthesis
Clinical Use:
Improved bioavailability of microemulsion form
Cyclosporine
Nephrotoxicity
Tremor
Hypertension
Hirsutism
MOA:
Binds to FKBP
Inhibits calcineurin and IL-2 synthesis
Clinical Use:
Improved patient and graft survival in (liver) primary immunosuppression and rescue therapy
Used as mainstay of maintenance protocol
Tacrolimus (FK506)
MOA:
Antimetabolite
Inhibits enzyme
necessary for de novo purine synthesis
CLINICAL USE:
Effective for primary immunosuppression in combination with tacrolimus
Mycophenolate mofetil
ADVERSE EFFECTS
Leukopenia
GI Toxicity
MOA:
Inhibits lymphocyte effects driven by IL-2 receptor
CLINICAL USE:
May allow early withdrawal of steroids and decreased calcineurin doses
Siroliums
## FOOTNOTE
ADVERSE EFFECTS
Thrombocytopenia Increased serum cholesterol/LDL
Poor wound healing
MOA:
Multiple actions
Anti-inflammatory Inhibits lymphokine
production
CLINICAL USE:
Used in induction, maintenance, and treatment of acute rejection
Corticosteroids
Cushingoid state
Glucose intolerance
Osteoporosis
MOA:
Antimetabolite
Interferes with DNA and RNA synthesis
CLINICAL USE:
Used in maintenance protocols or if intolerance to mycophenolate mofetil
Azathioprine
ADVERSE EFFECTS
Thrombocytopenia
Neutropenia
Liver dysfunction
MOA:
T-cell blocker
CLINICAL USE
New drug for maintenance immunosuppression in renal transplants only
Belatecept
Increased risk of bacterial infections
A chimeric anti-CD20 (anti-B cell) monoclonal antibody;
currently FDA approved for treating several types of lymphoma;
include the treatment of antibody- mediated rejection and use in desensitization protocols;
usually used in conjunction with plasmapheresis, steroids, and intravenous immunoglobulin (IVIG).
Rituximab
A proteasome inhibitor
for treating multiple myeloma. It can directly target plasma cells
shown to cause apoptosis of normal plasma cells, thereby
decreasing alloantibody production in sensitized patients
Bortezomib
humanized monoclonal antibody, for treating paroxysmal nocturnal hemoglobinuria, hemolytic uremic syndrome, and generalized myasthenia gravis
It blocks the activation of the terminal complement cascade
increased risk of infections: Neisseria meningitidis therefore meningococcal vaccine should be given at least 2 weeks before the administration
Eculizumab
Infection occuring within 1 month posttransplant can be due to a wide spectrum of pathogens
Early infection
2nd most common cause of graft loss in pancreas recipient after vascular thrombosis
Intra abdominal abscess
Signs and symptoms of intra-abdominal infections
Oeritonitis: fever, hypotension, ileus and abdominal pain
Intra abdominal infections are usually polymicrobial, these bacteria includes
E.coli, Enterococcus, Klebsiella and Pseudomonas spp.
For medical infections, what should be the treatment
Empiric antibiotics and anti fungal meds
infections that are primarily due to chronic immunosuppression, specifically the depression of cell-mediated immunity that renders recipients susceptible to viruses, fungi, and parasites.
Late infections
usually occur 3 to 6 months posttransplant or during treatment for rejection
the most common etiologic agents of viral infections posttransplantation
Herpesvirus group
Herpes simplex virus
Cytomegalovirus
Epstein Barr virus
Most prominent etiologic agent for viral infection
EBV
found in chicken, pidgeon, and bat droppings in the Ohio River and Mississippi River valleys.
Dissemination is commonplace; up to a quarter of patients have central nervous system (CNS) involvement.
Treatment consists of prolonged (3 to 13 months) administration of oral itraconazole.
Histoplasma capsulatum
grows in moist soil in the Midwest and Southeast regions of the United States.
Diagnosis is confirmed by biopsy; the preferred treatment is IV amphotericin B.
Blastomysis dermatitidis
cause invasive coccidioidomycosis after inhalation of aerosolized infectious particles. It is endemic in the Southwest, Northern Mexico, and various parts of Central and South America.
This infection can be resilient and difficult to treat.
The first line of treatment is high-dose amphotericin B.
Coccidiodes immitis
infections exhibiting a 20% mortality rate.
Prophylaxis with fluconazole has been shown to reduce invasive fungal infections in liver recipients
Candida or Aspergillus
species that are rare but can cause serious fungal infections
Aspergillus, Cryptococcus, Mucor and Rhizopus
is ubiquitous and can cause pulmonary disease in immunocompromised patients.
TMP-SMX is an effective prophylaxis
Pneumocystis jiroveci
Enumerate types of malignancies
Kaposi’s sarcoma
nonmelanoma skin cancer
non-Hodgkin’s lymphoma and
cancer of the liver, anus, vulva, and lip
