PCT V solid organ transplant exam 3

genetically dissimilar members of the same species

allogenic transplantation

transplantation of own self/cells

autologous transplantation

between genetically identical members of the same species

syngeneic transplantation

between species

xenogeneic transplantation

heterotopic

graft placement that is an engraftment of donor organs into an ectopic (different) location

heterotopic

kidney transplant is orthotopic/heterotopic

orthotopic

heart transplant is orthotopic/heterotopic

orthotopic

lung transplant is orthotopic/heterotopic

orthotopic

liver transplant is orthotopic/heterotopic

orthotopic

graft placement that is the removal of native organ and replacement of subsequent graft into the same place

- hypertension
- diabetes
- glomerulonephritis
- poly-cystic kidney disease
- re-transplant

indications for kidney transplant

- hepatitis B or C
- alcohol
- non-alcoholic steatohepatitis (NASH)
- autoimmune hepatitis

indications for liver transplant

- idiopathic cardiomyopathy
- ischemic heart disease

indications for heart transplant

- idiopathic pulmonary fibrosis
- COPD/emphysema
- cystic fibrosis
- idiopathic pulmonary arterial hypertension

indications for lung transplant

- immune cells/components
- major histocompatibility complex
- human leukocyte antigen (HLA)

components of the immune system

- antigens
- antigen presenting cells (APC)
- T and B lymphocytes
- immune organs

immune cells/components

- thymus
- bone marrow

primary immune organs (central)

environment/location for development and maturation of lymphocytes

action of primary immune organs

- adenoids
- tonsils
- peyers patch
- appendix
- lymph nodes
- spleen
- lymphatic vessels

secondary immune organs (peripheral)

- circulating antigens are "trapped" in these organs/locations
- "trapped" antigens can interact with mature lymphocytes in these organs/locations

action of secondary immune organs

foreign substance that is identified by the immune system as "abnormal" and produces an immune response

antigens

- cells that stimulate T-lymphocytes by presenting a foreign major histocompatability complex (MHC) molecule)
- generate antibodies against the graft (against HLA)

antigen presenting cells

- macrophages
- dendritic cells
- b-lymphocytes (b-cells)

antigen presenting cells examples

histocompatibility

ability of tissues to get along with each other

distinguishes "self" from "non-self"

function of major histocompatibility complex

major histocompatibility complex

every species has a unique...

human leukocyte antigen (HLA)

expressed on the surface of antigen presenting cells

T lymphocytes and B lymphocytes

types of lymphocytes

in the bone marrow

B lymphocytes develop where

B lymphocytes

antigen presenting cells are part of T/B lymphocytes

derived from bone marrow, differentiate in the thymus

T lympocytes are derived where

antigens

T lymphocytes have T cell receptors that bind to...

- Tc \= CD8 (cytotoxic T cells)
- Th \= CD4 (helper T cells)

types of T lymphocytes

destroy/kill infected target cells

function of Tc cells

stimulate other T and B cells

function of Th cells

T lymphocytes

T/B lymphocytes exhibits specificity towards an antigen

membrane attack complex

forms a transmembrane channel causing cell lysis and cell death

complement

can be recruited and activated by the immune response

- opsonization: enhancing phagocytosis of antigens
- chemotaxis: attracting macrophages and neutrophils
- cell lysis: rupturing membranes of foreign cells
- agglutination: clustering and binding of pathogens together (sticking)

function of complement immune system

membrane attack complex

complement cascade is one of the pathways to develop...

highe PRA

higher immunosuppression is required with low/high PRA (panel of reactive antibodies)

increased

PRA (panel of reactive antibodies) has an increased/decreased likelihood of a positive cross match

- identification of presence of donor specific antibodies (DSA)

crossmatching

positive

positive/negative crossmatch can lead to hyperacute rejection

false

T/F crossmatching is not required before transplant

true

T/F crossmatching is required before transplants

false, immunosuppression is always required

T/F a PRA of 0% indicates no immunosuppression is required

true

T/F a PRA of 0% still requires immunosuppression

combining recipient serum with a sample of the general donor pool's most common antibodies and looks for a reaction

how is a PRA calculated

prevent immune system from attacking the transplanted organ aka causing a rejection

function of anti-rejection drugs (immunosuppressive drugs)

true

T/F patient will take immunosuppressive drugs for the rest of their life

false, will take for the rest of their life

T/F patient will take immunosuppressive drugs until their immune system becomes accustomed to the new organ

rejection or organ failure

not taking/missing immunosuppressive drug dose can result in...

2-3

most kidney, heart or lung transplant patients will be on how many immunosuppressive drugs

start on 3, and be maintained on 1 or 2

most liver transplant patients will start out on how many immunosuppressive drugs

- methylprednisolone
- prednisone

corticosteroid immunosuppressants

- anti-thymocyte globulin
- muronomab CD3
- basiliximab (daclizumab)
- alemetuzumab
- rituximab
- bortezomib
- eculizumab

biologic immunosuppressants

- mycophenolate
- azathiprine

antimetabolite immunosuppressants

- tacrolimus
- cyclosporine

calcineurin inhibitor immunosuppressants

- sirolimuc
- everolimus

MTOR inhibitor immunosuppressants

belatacept

fusion protein immunosuppressants

- short-term therapy used at the time of transplant
- high level of immunosuppression (higher doses of maintenance agents and antibody agents/biologics)

induction of immunosuppressants

- prevent acute and chronic rejection while minimizing drug-related toxicity
- multiple agents used (target different sites of immune response activation)
- long-term
- primarily oral

maintenance of immunosuppressants

monoclonal

from a single cell line, directed against a single epitope

polyclonal

combination of immunoglobulin molecules directed against a specific antigen (multiple epitopes)

depleting

removes lymphocytes from circulation

nondepleting

inhibits activity but does not remove cells

humanized

derived from human cells

chimeric

derived from part human and part nonhuman cells

basiliximab

monoclonal, non-depleting induction agent

- rituximab
- alemtuzumab

monoclonal, depleting induction agent

- equine antilymphocyte globulin (atgam)
- rabbit antithymocyte globulin (thymoglobulin)

polyclonal, depleting induction agent

chimeric

basiliximab is humanized/chimeric

induction only
cannot treat rejections!

indication for basiliximab

antithymocyte globulin (atgam)
use thymoglobulin instead

question use of rabbit-antithymocyte globulin (thymoglobulin)/antithymocyte globulin (atgam) in solid organ transplant

pre-medicate with acetaminophen, diphenhydramine and steroids

administration of antithymocyte globulin (atgam)

- induction: high risk patients (PRA \> 80%) and those at increased risk of delayed graft function
- rejection

rabbit-antithymocyte globulin (thymoglobulin) indications

\> 80%, and thymoglobulin should be recommended for induction

what PRA level is considered a high risk patient

- pre-medicate with acetaminophen, diphenhydramine and steroids (or similar medications)

administration of rabbit-antithymocyte globulin (thymoglobulin)

anti-thymocyte globulin (atgam)

which anti-thymocyte has more serum sickness

rabbit-antithymocyte globulin (thymoglobulin)

which anti-thymocyte is less immunogenic

rabbit anti-thymocyte globulin (thymoglobulin)

which anti-thymocyte causes less serum sickness

anti-thymocyte globulin (atgam)

which anti-thymocyte globulin is more immunogenic

rabbit anti-thymocyte globulin (thymoglobulin)

which anti-thymocyte has less recurrent rejection

anti-thymocyte globulin (atgam)

which anti-thymocyte has more recurrent rejection

rabbit anti-thymocyte (thymoglobulin)

which anti-thymocyte globulin has higher rates of rejection reversal

anti-thymocyte globulin (atgam)

which anti-thymocyte globulin has lower rates of rejection reversal

rabbit anti-thymocyte globulin (thymoglobulin)

which anti-thymocyte has better overall graft survival

anti-thymocyte globulin (atgam)

which anti-thymocyte has worse graft survival

- cytokine release syndrome
- chills
- fever
- infection
- leukopenia
- malignancy
- thrombocytopenia

adverse effects of rabbit anti-thymocyte globulin (thymoglobulin)

- infection
- malignancy

adverse effects of basiliximab

20mg IV on post op days 0 and 4

basiliximab dose

short

basiliximab has a short/long infusion time

peripherally

basiliximab is given peripherally/centrally

atgam

brand name for antithymocyte globulin

thymoglobulin

brand name for rabbit antithymocyte globulin

10-15mg/kg/day IV for 7-10 doses
- adjust dose for leukopenia and/or thrombocytopenia

dose for antithymocyte globulin (atgam)

run for 4-8 hours

duration of antithymocyte globulin (atgam) dose

central

antithymocyte globulin (atgam) is given via peripheral/central line

1.5mg/kg/day IV for 3-5 doses
- adjust for leukopenia and/or thrombocytopenia

dose for rabbit-antithymocyte globulin (thymoglobulin)