M9 Flashcards
process of transferring an organ, tissue, or cell from one place or another
Transplantation
surgical procedure in which a failing organ is replaced by a functioning one.
organ transplant
implanted in the same anatomic location in the recipient as it was in the donor.
Orthotropic
implanted in another location.
Heterotropic
represent the most reliable way to achieve euglycemia in patients with uncontrollable diabetes
Pancreas transplantation
normal response to glucose
Euglycemia
has become the standard of care for many patients with end-stage liver failure and/or liver cancer
Liver transplantation
“Saving lives together”
UNITED NETWORK FOR ORGAN
SHARING (UNOS)
first hospital in the Philippines accredited to perform kidney transplant
NKTI
Is a potentially lifesaving treatment for end-stage organ failure, cancers, autoimmune diseases, immune deficiencies, and a variety of other diseases
TRANSPLANTATION
largest immunologic barrier to successful allogeneic organ transplantation consist of cell surface proteins which play a central role in immune recognition and initiation of immune responses
HLA (Human Leukocyte Antigen) system
The HLA (Human Leukocyte Antigen) system’s largest immunologic barrier to successful _____ consist of cell surface proteins which play a central role in immune recognition and initiation of immune responses
allogeneic organ transplantation
Is a cluster of genes found on the short arm of chromosome 6 at band 21
Major histocompatibility complex (MHC)
key element in organ transplantation
Organ procurement
Typically, brain death is defined as the ___ of brain function, including the brainstem.
irreversible cessation
The presence of medical conditions that mimic brain death - _____- need to be excluded.
such as drug overdose, medication side effects, severe hypothermia, hypoglycemia, including coma, and chronic vegetative state
The clinical diagnosis of brain death consists of four essential steps:
Establishment of the proximate cause of the neurologic insult.
Clinical examinations to determine coma, absences of brainstem reflexes, and apnea.
Utilization of ancillary tests, such as electroencephalography (EEG), cerebral angiography, or nuclear scans, in patients who do not meet the clinical criteria.
Appropriate documentation. A similar guideline in determining brain death in pediatric patients was recently developed.
Given the severe shortage of donor organs, donation after cardiac death (DCD) - also known as the
___
donation by non-heart beating donors (NHBDs)
donation by non-heart beating donors (NHBDs) - was reintroduced to the transplant community in the __
1990s
The category of DCD (_____)was initially proposed at an international workshop and is now widely adopted for organ procurement.
Maastricht classification)
Most NHBDs in the United States meet __ that is, they have suffered a devastating injury with no chance of a meaningful recovery but do not meet the criteria for brain death.
Maastricht classification III;
With cardiac death (as opposed to brain death), _____ to organs can occur during the period between______ through perfusion of preservation solution.
warm ischemic injury, circulatory cessation and rapid core cooling
The maxim of medical ethics is ____ (first, do no harm), and for that reason living organ donation presents unique ethical and legal challenges
“primum non nocere”
Recipient should have a maximum benefit
Beneficence
The____ adopted by all states in the United States (with slight variations) provides the legal framework for competent adult living donors to decide whether to donate.
Uniform Anatomical Gift Act
For a nephrectomy (kidney), the estimated mortality risk is less than ___
For a partial hepatectomy (liver), about ___
0.05%, 0.2%
The guiding principle should be ___
minimization of risk to the donor.
Kidney
YEAR:
SURGEON:
YEAR: 1954
SURGEON: JOSEPH E. MURRAY
LIVER
YEAR:
SURGEON:
LIVER
YEAR: 1963
SURGEON: THOMAS E. STRAZL
LUNG
YEAR:
SURGEON:
LUNG
YEAR: 1963
SURGEON: JAMES D HARDY
PANCREAS
YEAR:
SURGEON:
PANCREAS
YEAR: 1966
SURGEON: RUCHARD C. LILLEHEI
HEART
YEAR:
SURGEON:
HEART
YEAR: 1967
SURGEON: CHRSTIAN N. BARNARD
SMALL INTESTINE
YEAR:
SURGEON:
SMALL INTESTINE
YEAR: 1967
SURGEON: RICHARD C LILLEHEI
HEART/LUNG
YEAR:
SURGEON:
HEART/LUNG
YEAR: 1981
SURGEON: BRUCE REITZ
MULTIVISCERAL
YEAR:
SURGEON:
MULTIVISCERAL
YEAR: 1989
SURGEON: THOMAS E. STARZL
Class I
(HLA-A, B, and C)
Class II
(HLA-DR, DQ, and DP) proteins
HLA genes are inherited as___from parental chromosomes
haplotypes
HLA genes are linked and inherited in __ as haplotypes.
MEDELIAN FASHION
_____molecules consist of an alpha chain, a highly polymorphic glycoprotein, encoded within the MHC on chromosome 6.
Class I HLA
This___ is noncovalently associated with beta-2 microglobulin, a non polymorphic glycoprotein, encoded by a nonHLA gene on chromosome 15.
alpha chain
Most nucleated cells
HLA CLASS A
To present endogenous antigen to helper T lymphocytes
HLA CLASS II
To present endogenous antigen to cytotoxic T lymphocytes
HLA CLASS I
B lymphocytes, macrophages, other antigen-presenting cells, activated T lymphocytes
HLA CLASS II
Class II HLA molecules are composed of____encoded within the MHC
alpha chains and beta chains
___molecules bear no clear relationship to class I and II molecules aside from their genetic linkage (presence of the gene in or near the MHC complex).
Class III
Class III molecules are involved in immunologic phenomena because they represent components of the___
complement pathways.
Complement System gene products such as____complement components are incomplete but these structures are defined by genes lying between or very near the HLA-B and HLA-DR loci.
C2, C4A, C4B, and Bf
The presence of HLA was first recognized when___experienced transfusion reactions despite proper crossmatching.
multiple transfused patients
It was discovered that these reactions were caused by ____rather than by antibodies directed against erythrocyte antigens.
leukocyte antibodies
Transplants are rejected if performed against ___; thus, immunosuppressive therapy is required.
MHC barriers
In organ transplantation, it is important to always consider ___
ABO compatibility and HLA testing
The____ can also bind to self-antigens produced in the normal process of ___. Usually, these are not recognized by the T cell receptor (TCR; tolerance).
class I and class II molecules, cellular protein degradation
In transplant patients, most immune responses are generated not from bacterial antigens, viral antigens, or self-antigens, but from the presentation of alloepitopes derived from the___
transplanted tissue to circulating T lymphocytes.
In kidney allografts, all of the following are important determinants of early transplantation success or failure:
The method of organ preservation
The time elapsed between harvesting and transplanting
The number of pre-transplantation blood transfusions
The recipient’s age (the younger, the better)
The primary cause for kidney failure
___ are added; will cool the organ to prevent damage
preservatives
*Ankylosing spondylitis
Reiter’s syndrome
B27
Psoriasis vulgaris
Cw6
Rheumatoid arthritis
DR4
Behcet’s disease
B5
Type 1 diabetes
DR3
Congenital adrenal hyperplasia
B47
DR5
Gold-induced nephropathy
Chronic lymphatic leukemia
Kaposi’s sarcoma (Mediterranean)
Transplantation of cells or tissues between two individuals is classified by the genetic relatedness of the donor and the recipient.
ALLORECOGNITION
The transfer of tissue from one area of the body to another of the same individual.
AUTOGRAFT
The transfer of cells or tissues between identical twins.
SYNGENEIC GRAFT
The transfer of cells or tissue between two individuals of the same species.
ALLOGRAFT
The transfer of tissue between two individuals of a different species.
XENOGRAFT
Recipient T cells bind and respond directly to foreign (allo) HLA proteins on graft cells
DIRECT ALLORECOGNITION
Second-pathway by which the immune system recognizes foreign HLA proteins
INDIRECT ALLORECOGNITION
As it involves the uptake, processing, and presentation of foreign HLA proteins by recipient antigen-presenting cells to recipient T-cells
INDIRECT ALLORECOGNITION
It plays a predominant role in the acute and chronic rejection
INDIRECT ALLORECOGNITION
APC cause production of cytokines and antibody
INDIRECT ALLORECOGNITION
Polymorphic genetic system that impacts allogeneic transplantation
KILLER IMMUNOGLOBULIN-LIKE RECEPTORS
one of several types of cell surface molecules that regulate the activity of natural killer (NK) lymphocytes; NK cells attach to receptors.
KILLER IMMUNOGLOBULIN-LIKE RECEPTORS
It is the acquisition of nonreactivity toward particular antigens.
IMMUNOLOGIC TOLERANCE
Included among the functions of NK cells are secretion of ____
cytokines and non-MHC restricted cytotoxicity.
Do not show a marked difference in tolerance at different stages of maturation
T CELL TOLERANCE
Immature T cell clones may be aborted in a manner similar to that of B cells (e.g. apoptosis).
Clonal abortion
The subsets of a mature T cell may be individually deleted, leading to the loss of only one of the functions of the T cell group (subsets are the only ones deleted).
Functional deletion
T cell suppressors actively suppress the actions of other T cell subsets or B cells
T cell suppression
A low concentration of multivalent antigen may cause the immature clone to abort.
Clonal abortion
Clonal abortion
A low concentration of multivalent antigen may cause the immature clone to abort.
Tolerance of ____
immature B cells by this mechanism is high.
Clonal exhaustion
Repeated antigen challenge with a T-independent antigen may remove all mature functional B cell clones.
Tolerance of ____
mature B cells is moderate.
Functional deletion
The combined absence of the helper T subset and presence of T-dependent antigen (or with T suppressor cells), or an excess of T-independent antigen, prevents mature B cells from functioning normally.
The ability to tolerate___
B cells by this mechanism is moderate.
Antibody-forming cell blockade
An excess of T-independent antigen interferes with the secretion of antibodies by antibody-forming cells.
____
B cell tolerance by this mechanism is low.
Used because the CD3 surface membrane marker is found on all mature post-thymic T cells
MONOCLONAL ANTIBODIES
Interaction between ___ and the surface of mature T lymphocytes causes T cell depletion
OKT3
The use of OKT3 reverses almost all_____
acute renal transplant rejection
Is indicated for the treatment of steroid-resistant rejection.
MONOCLONAL ANTIBODIES
NULOJIX
Belatacept
This type of drug is called a selective T cell costimulation blocker.
NULOJIX
MYCOPHENOLATE MOFETIL
RS-61443
MYCOPHENOLATE MOFETIL
Inhibits___
de novo guanosine synthesis
By inhibiting inosine monophosphate dehydrogenase
This drug inhibits T and B lymphocyte proliferation and antibody formation by B lymphocytes
MYCOPHENOLATE MOFETIL
Has been efficacious as prophylactic and rescue therapy in refractory renal allograft rejection in clinical trials.
MYCOPHENOLATE MOFETIL
SIROLIMUS
Rapamune
Previously referred to as rapamycin
Sirolimus is derived from the fungus ____ from the soil of Easter Island.
Inhibits the activation and proliferation of T lymphocytes and subsequent production of _____
Sirolimus also inhibits antibody production
Streptomyces hygroscopicus ,IL-2, IL-4, and IL-15.
TACROLIMUS
A macrolide with mechanisms similar to cyclosporine, is derived from a fungus, Streptomyces tsukubaensis
Its primary target appears to be the Th lymphocytes
With little effect on other aspects of the immune response.
TACROLIMUS
TACROLIMUS
FK 506
FK-506 acts early in the process of T cell activation and inhibits the production of ___
IL-2.
Isolated in 1971 from the fungus Tolypocladium inflatum
CYCLOSPORINE (CYCLOSPORIN A)
Has become the mainstay of immunosuppressive therapy in transplantation
CYCLOSPORINE (CYCLOSPORIN A)
Cyclosporine blocks ____transcription pathway and the release of certain other lymphokines (e.g., IFN-γ).
calcineurin to the IL-2 gene
Directly inhibit antigen-driven T cell proliferation
CORTICOSTEROIDS
nhibit production of lymphokines by preventing monocytes from releasing IL-1
CORTICOSTEROIDS
High doses of ___are used to treat acute rejection.
corticosteroids
Post-transplantation steroid-induced hyperglycemia can produce physiologic conditions that negatively affect a graft.
Diabetes
An increased blood cholesterol is a serious post-transplantation concern because of long-term vascular effects to the patient and engrafted organ. Hypercholesterolemia can result from the return of the patient’s appetite and the lifting of dietary restrictions.
Hypercholesterolemia
The most common approaches for analysis include PCR amplification of HLA genes with panels of primer pairs, each of which amplifies specific alleles or related allele groups.
GENOTYPING
only those primer pairs that bind to the target gene result in detection of an _____
amplification product
The amplified gene is then subjected to hybridization with a ____ each specific for a unique HLA allele or allele group.
Only those probes that specifically hybridize to the amplified DNA will be detected.
Panel of DNA probes,
The classic procedure for determining the HLA phenotype is the ___
complement-dependent cytotoxicity (CDC) test
____ are used for HLA class I typing, while purified B lymphocytes are used for HLA class II typing.
Purified T lymphocytes
