Fetal Transplant

Question 1

What is an autograft, isograft, allograft, xenograft?

Answer 1

auto-same
iso-identical twin
allo-person to person
xeno-species to species

Question 2

What are the barriers to transplant?

Answer 2

Rejection

MHC

Question 3

What two things must you determine before transplant?

Answer 3

1. Detection of recipient antibodies that might cause rejection transplanted organ
2. Determination of the degree of compatibility between the recipient

Question 4

What is a histocompatibility complement dependent cytotoxicity assay?

Answer 4

Determine whether the acceptor has antibodies that will react with donor= histocompatibility

1. take patents serum (with potential antibodies in it) and react it with the mhc antigens class 1 and class 2 of the donor lymphocytes
2. if there are antibodies they will bind their MHC antigen
3. Complement is then added
4. lymphocytes that have bound antibodies will be lysed
   - ->since the mhc is known for each well, you can tell exactly which anti-MHC are present in the acceptor serum

Question 5

What is a mixed lymphocyte culture called MHC typing?

Answer 5

basically a transplant in-vitro
Taking cells from the recipient will they reject the organ
1. Take cells from the recipient and put them into culture and mix them with cells from the donor
2. Paralyze cells of the donor-still have MHCs but they can’t multiply(just displaying)
3. See if the recipient cells proliferate and have cytotoxic response to donor cells you know the graft is not going to work

Question 6

What are new approaches to histocompatibility?

Answer 6

Flow cytometry
ELISA
Molecular 
-decrease time
-increase  cost 
-increase sensitivity

Question 7

What will the intensity of rejection be determined by?

Answer 7

1. Differences in MHC
2. Host immune response genes
3. Physician Interventions

Question 8

What is direct vs indirect allorecognition?

Answer 8

Indirect: Normal, Graft sheds antigens those antigens are recognized by APCs which process proteins and present them in MHC2

Direct: host dendritic cells recognize donor mhc as an entire antigen
-skipping processing part

*happening in lymph node

Question 9

Dendritic cells from the donor are called what?

Answer 9

passenger leukocytes

Question 10

What response are in rejection of graft?

Answer 10

Th1- TMMI or CD8
Th2- graft specific antibody
IL 17 
Neutrophils 
NK cells

Question 11

What is hyperacute rejection?

Answer 11

Patient has pre-existing antibodies to the graft you are about to put into the recipient

• as soon as you put it in it is immediately rejected
• immediately vascular system occludes blood vessel
• no platelets can get in

Question 12

What is an acute rejection?

Answer 12

Defined by sudden (10-90 days)
appearance of effector cells in the graft

-mononuclear cells trying to attack muscle tissue (T cells, NK, Macrophages)

Vigor depends upon Dr(MHC2) mismatch, gender, intensity of immunosuppression

Question 13

What can arrays tell you?

Answer 13

can distinguish between acute and chronic rejection and drug toxicity

• can tell what cells are reacting
• can see if there are Tregs

Question 14

What is Chronic rejection?

Answer 14

repeated rejection

• causes organ damage
• ->fibrosis
• caused by mechanism probably different than acute rejection,
• usually caused by intimal thickening that leads to graft ischemia –>slowly chokes graft off from blood supply
• major problem in solid organ transplant today (lung transplants)

Question 15

What are strategies to prevent rejection?

Answer 15

1. optimal MHC matching especially MHC2
2. block t cell responses to alloantigens
3. provide:
   - Inhibitory second signals (CTLA
   4)

• T regs cells (CD4,25)
• Cytokines (Il 21, 23, 10 and tgf-b that override Th1, Th17 and CD8)
  4. induce tolerance by manipulating Tregs ***

Question 16

What is the difference between Transplant rejection (kidney) and Graft vs host disease (Bone marrow)?

Answer 16

Kidney: when the recipient’s T cells attack the transplant

Bone Marrow: T cells in transplant attack the recipient tissue

Question 17

Do we have antibody to alpha 1, 3 GT gene?

Answer 17

yes

Question 18

Why is xenotransplant difficult?

Answer 18

1. Hyperacute rejection (if they have gene 1,3 GT) -preformed antibodies

if survive hyperacute rejection
2. acute chronic rejection because MHCs are very different

3. viruses animals have

Question 19

How have pigs been genetically engineered to be used for transplant? What are remaining problems?

Answer 19

Human complement regulating proteins inserted on pig cell surfaces

a. inhibit hyperacute rejection at least in part
b. removal of alpha-gal determinant from pig cell surface

Problems: antipig, non-gal antibodies, and conventional acute and chronic rejection

Question 20

What does mom do to the babies MHC 1 and 2?

Answer 20

Mom turns of Trophoblast MHC 1 and 2 so her immune system doesn’t recognize it
-only public now shows common

Question 21

How are NK cells different in utero?

Answer 21

MHC complex HLA-G-inhibitory for NK cells

-changes NK cells that in uterine–look different and act different–act like NK regs produce TGF B and IL 10

Question 22

What promotes Tregs in the uterus?

Answer 22

HLA g and TGF B promote differentiation of T regs

Question 23

What are gammdelts like in utero?

Answer 23

immuno regulatory

Question 24

What happens when maternal lymphocytes come in contact with fetal t-lymphocytes?

Answer 24

-when maternal T lymphocytes that come in common with fetal t lymph-fetal turn them off

Question 25

What hormone supresses Th1 responses in mom? What bias does this lead to during gestation? What responses decrease?

Answer 25

Progesterone suppresses TH1 reactions

• TH2 bias during gestation
• TMMI responses down and CD 8, CD 4
• spills over into her systemic system

-when you have Th1 early you are going to get abortion

Question 26

What happens if the futus gets infected with somethings?

Answer 26

-if fetus gets infected it becomes tolerant to it, and it may cause abnormalities