Exam 4 Lecture 21: Transplantation Flashcards
What is the role for the immune system in transplantation?
Requires inactivation of the immune system
3 major types: liquid (blood), solid, and hematopoietic
Includes a donor and a recipient
Histocompatibility
When donor and recipient have “similar” tissue types, based on fewer differences between antigens
Closer the histocompatibility, more chance of success
Alloantigens
Antigens that differ between genetically unrelated individuals in a species and can cause incompatibility, common for polymorphic loci, depends on what is being
transplanted
ex. (A, B, O) (Rhd)
Genetic polymorphisms
the occurrence in a population of two or more alleles at one
genetic locus, each with significant frequency
Liquid (blood) transplants
- Can be donated repeatedly by healthy individuals
- Cheap and non-invasive
- No HLA I or II expressed on erythrocytes, so no need for HLA compatibility
- Mostly used for acute/transient needs
Blood components:
* erythrocytes (RBCs)- oxygen exchange and metabolism
* plasma– fluid replacement
* platelets- facilitates clotting and prevents excessive bleeding
What are A and B antigens?
How do differences in ABO blood type determine who can donate blood to a particular individual?
- Erythrocyte surface antigens differ
in glycolipid carbohydrates - Due to specific glycolipid additions,
the A and B antigens can stimulate a
foreign immune response when
transfused into recipients that have
not previously seen them
Blood transfusion incompatibility
Leads to type II hypersensitivity:
erythrocyte (red blood cell)
lysis, fever, chills, shock, kidney
failure, and death
What is the Cross-Match test and what does it measure?
Apart from ABO and RhD antigens, there are additional potential blood group polymorphic antigens that could cause incompatibility, but too many to test individually
Cross-Match Test is used to test whether patient
antibodies in the serum react with donor blood that is ABO and RhD- matched
What is the antigen most commonly recognized by alloreactive T cells during solid
organ transplants and why?
MHC molecules
- During organ transplantation, a donor organ is
transplanted into an intact recipient immune system - Every individual has a subpopulation of naïve
“alloreactive” T cells that are specific for non-self
MHC antigens - Alloreactive T cells could react to the
antigens in the donated organ - Immune reactions to MHC are common
because they are the most polymorphic
proteins - Transplant rejection occurs because the
recipient immune system attacks the
donor tissue.
What are the differences between hyperacute, acute, and chronic rejection of solid
organ transplants?
Hyperacute: minutes to hours
Type II
Mechanism: pre-existing antibodies against blood antigens or MHC
Cause: pregnancies, previous transfusions or transplants
Treatment: none
Acute: days
Type IV
Mechanism: allorecognition” by donor dendritic cells that prime recipient T cells which then migrate to the graft -> CD4 T cells release cytokines -> inflammation. CD8 T cells kill cells in the graft
Treatment: avoided by the use of immunosuppressive drugs prior to transplant & suppression of immune system
Chronic: years
Type III
Mechanism: IgG specific for graft HLA that causes immune complex
formation
(Table on slides)
What is the difference between direct and indirect allorecognition? And how does MHC matching improve chances for transplant survival?
Direct allorecognition: Donor HLA class I
and II on a donor DC stimulates recipient T
cells
Indirect allorecognition: Donor HLA class I
and II are endocytosed and processed by recipient DC and presented on the recipient HLA
How do you set up a mixed-lymphocyte reaction and what does it test for?
Assess ahead of time how the patient’s T cells will respond to a transplanted organ
Donor cells are irradiated so antigens can stimulate other cells but not respond themselves -> Donor cells are co-cultured with recipient cells for 5 days -> Measure recipient cell proliferation (tests the magnitude of alloreactive reaction) & Measure recipient cell killing of donor cells (tests the capacity for graft rejection)
What are the mechanisms of action of the following immunosuppressive drugs:
Prednisone
Belatacept
Anti-CD25
Medicines that lower the body’s ability to
reject a transplanted organ
Work best when given just before surgery
Prednisone: synthetic derivative of cortisol and the
corticosteroid most commonly used prior to organ
transplantation
Mechanism- inhibits NF-kB activation by increasing
production of an NF-kB negative regulator -> prevents
lymphocyte migration which inhibits naïve lymphocyte
activation and attack on the organ
Belatacept: fusion of CTLA4 with Fc antibody subunit
Mechanism- inhibits T cell co-stimulation by
competing with CD28 for binding to B7 and blocking signal 2
Anti-CD25: antibody
Mechanism- targets the high affinity
IL-2R on activated T cells to block early T cell activation
What is a hematopoietic cell transplant
Aka bone marrow transplant
Used when the patient’s hematopoietic system is diseased due to cancers or genetic diseases
Patient has mature immune cells wiped out with irradiation or chemotherapy
Transplant is easier to donate than solid organ
HLA match is required
In hematopoietic cell transplants, why must there be at least a partial MHC match between donor and recipient?
Immune reconstitution slides
