Week 3: Transplantation and Alloimmunity

Question 1

Term for immune response to tissues that are dissimilar

Answer 1

Alloimmunity

Question 2

What are the 3 versions of alloimmunity? (When could you activate alloimmunity?)

Answer 2

Transient Neonatal Alloimmunity
Transfusion Reaction
Transplantations Reactions

Question 3

In Transient Neonatal Alloimmunity, what are the 2 general ways of alloimmunity occurrence?

Answer 3

1) Fetal antigens interacting with mother antibodies

2) Maternal Autoimmune Disease

Question 4

What category of alloimmunity is Hemolytic Disease of the newborn in? Describe the disease, another name for it, percent mortality, and treatment for it.

Answer 4

Category: Transient Neonatal Alloimmunity (Fetal antigen/ maternal antibody)

Description:
Occurs when Rh- mother makes a baby with Rh+ dad. The baby gets Rh+ blood.
The Rh+ blood crosses the placenta and the mother’s immune system makes antibodies to fight off the antigens in the blood of the baby. It does not usually affect the first baby as much, but can be fatal for the second baby because the mother still has the antibodies. This would cause the antibodies to attack the baby’s blood.
IgD antibodies are usually the antibodies that are involved with this disease because they are more incompatible than other antigens.

Mortality Rate: 50% mortality rate with no intervention

Treatment:
RhoGAM is used by a prophylactic injection of anti-Rh antibodies.
This injection of antibodies binds to the baby’s antigen and prevents the mother’s antibodies from recognizing them as foreign.

Question 5

What category of alloimmunity is Neonatal Alloimmune Thrombocytopenia? Describe the disease, percent mortality, prevalence, and treatment for it.

Answer 5

Description:
Works similar to hemolytic disease except it involves platelets. The baby would exhibit low levels of platelets and could have small ruptures (petechial bleeds) or a bruised head (cephalohematoma).
This disease typically involves many factors. It is the most common cause of severely decreased platelets and intracranial bleeding as an infant. Has a mortality rate of 10% with no intervention.

Prevalence:
1 in 1000-1500 births
60% of cases are in first pregnancies.

Treatment:
Usually resolves in 2-3 weeks without treatment

Question 6

Describe Transient Neonatal Alloimmunity caused by maternal autoimmune diseases. What kind of hypersensitivity would this be considered?

Answer 6

The mother has an autoimmune disease. Her self-attacking antibodies cross the placenta into the fetus and bind to antigens in the fetus. This will cause the fetus to exhibit the same autoimmune disease characteristics as the mother. The effects are usually not permanent and rarely lethal. Once the maternal antibodies degrade, the symptoms in the fetus will resolve.

Considered type 2 hypersensitivity.

Question 7

What happens during a transfusion of the wrong blood type or mismatched Rh proteins? What organ usually is greatly affected by this? What kind of hypersensitivity is this?

Answer 7

IgG or IgM (mostly IgG) destroy the mismatched blood through agglutination and lysis of the RBC. Can cause ischemia. Properdin binds to complement C3 in the donor blood which activates the alternative pathway cascade. The donor becomes coated with IgG and is removed by macrophages.

The kidneys are greatly affected because they are trying to filter out all of the RBC’s.

Type 2 hypersensitivity

Question 8

When referring to types of transplants (Allogenic, Syngeneic, Xenogenic, Autologous), what is the order from going most effective to least effective?

Answer 8

Autologous, Syngeneic, Allogenic, Xenogenic

Question 9

self-transplant

Answer 9

Autologous

Question 10

transplant between identical twins

Answer 10

Syngeneic

Question 11

Transplant between individuals of the same species

Answer 11

Allogenic

Question 12

transplant between different species

Answer 12

Xenogenic

Question 13

Organ Transplant Criteria

Answer 13

Irreversible organ damage
No alternative treatment options
Non-recurring disease
Transplant compatibility

Question 14

When determining transplant compatibility, what must be taken into account?

Answer 14

The specific organ required, the blood compatibility, and haplotype matching.

Question 15

What are some things that disqualify a person from receiving a transplant?

Answer 15

Chronic infection
Cancer
Drug or alcohol use disorder
Inadequate social support
Obesity
Uncontrolled diabetes
Poor adherence to prior treatment

Question 16

What is the most important HLA gene when determining the compatibility of a transplant?

Answer 16

HLA-DR

Question 17

The DRα chain and its mouse homolog Eα are considered to be ___________ because they do not vary in sequence between different individuals.

Answer 17

monomorphic

Question 18

There is a ____chance of matching between siblings who share the same parents.

Answer 18

25%

Question 19

If a patient is an exact match for blood types and haplotypes and receives a transplant but it is rejected, what might’ve caused that?

Answer 19

Minor histocompatibility antigen mismatches are associated with the MHC molecules.
The proteins of the donor may have had different amino acid sequences which are not detected by standard tissue typing techniques. These are coded outside the HLA regions.

Question 20

The cellular process of transplant rejection is primarily _____________.

Answer 20

cell-mediated

Question 21

How are transplant rejections categorized?

Answer 21

By the time that it takes to reject the tissue.

Question 22

3 categories of transplant rejection

Answer 22

Hyperacute- minutes to hours
Acute- first days to weeks
Chronic- years

Question 23

5 causes of transplant rejection

Answer 23

Donor Class I MHC molecules 
Donor Class II MHC molecules
ABO molecules
Endothelial antigens (vascular tissue)
Minor HLA

Question 24

Explain hyperacute transplant rejection.

Answer 24

Occurs within minutes of transplantation.
The recipient had past exposure to the alloantigens and created antibodies for them in the past. This could be because of previous blood transfusions, previous grafts, or having been pregnant with multiple partners.
AB targets Ag in the donated tissue activating plasma protein systems (complement, etc) and leukocyte infiltration. Leads to massive blood clots in the capillaries of the transplanted tissue. Causes the tissue to receive little to no oxygen.
The transplant turns white. Called “white graft”

Question 25

2 types of acute transplant rejection

Answer 25

Cell mediated and Humoral Destruction

Question 26

Describe cell-mediated acute graft rejection.

Answer 26

Makes up 90% of acute rejection cases.
Direct Pathway. Reacts to MHC I complex.
T-cell-mediated reactions.
Occurs within days of transplantation.
Graft gets infiltrated by macrophages due to foreign MHC molecules on donors APC cells
Can be minimized/prevented via immunosuppressant drugs
Damage to the endothelial cells of the donor is the reason for rejection.

Question 27

Describe antibody-mediated rejection in acute transplant rejections.

Answer 27

Occurs 10% of time.
Indirect Pathway. Involves MHC II complex.
Occurs days to weeks.
B-cells are activated and produce antibodies for the graft antigens. The complement system is activated and causes an accumulation of antibodies, complement, and neutrophils. Clotting occurs in the blood vessels of the transplanted tissue