M9 Flashcards by pink popcorn

process of transferring an organ, tissue, or cell from one place or another

Transplantation

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surgical procedure in which a failing organ is replaced by a functioning one.

organ transplant

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implanted in the same anatomic location in the recipient as it was in the donor.

Orthotropic

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implanted in another location.

Heterotropic

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represent the most reliable way to achieve euglycemia in patients with uncontrollable diabetes

Pancreas transplantation

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normal response to glucose

Euglycemia

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has become the standard of care for many patients with end-stage liver failure and/or liver cancer

Liver transplantation

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“Saving lives together”

UNITED NETWORK FOR ORGAN
SHARING (UNOS)

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first hospital in the Philippines accredited to perform kidney transplant

NKTI

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Is a potentially lifesaving treatment for end-stage organ failure, cancers, autoimmune diseases, immune deficiencies, and a variety of other diseases

TRANSPLANTATION

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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

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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

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Is a cluster of genes found on the short arm of chromosome 6 at band 21

Major histocompatibility complex (MHC)

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key element in organ transplantation

Organ procurement

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Typically, brain death is defined as the ___ of brain function, including the brainstem.

irreversible cessation

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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

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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.

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Given the severe shortage of donor organs, donation after cardiac death (DCD) - also known as the
___

donation by non-heart beating donors (NHBDs)

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donation by non-heart beating donors (NHBDs) - was reintroduced to the transplant community in the __

1990s

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The category of DCD (_____)was initially proposed at an international workshop and is now widely adopted for organ procurement.

Maastricht classification)

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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;

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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

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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”

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Recipient should have a maximum benefit

Beneficence

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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

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

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