Alloimmunity

Question 1

alloimmunity

Answer 1

immune response to genetically dissimilar tissue

Question 2

transient neonatal immunity- 2 causes

Answer 2

• fetal Ag/maternal Ab

- maternal autoimmune disease

Question 3

transient neonatal immunity caused by fetal Ag/maternal Ab

Answer 3

1) fetal Ags cross the placenta
2) elicit an immune response in the mother
3) maternal Abs (IgG) cross the placenta and bind fetal Ags
4) fetal immune system respons to maternal Abs

Question 4

2 types of transient neonatal immunity caused by fetal Ag/maternal Ab

Answer 4

• hemolytic disease of the newborn

- neonatal alloimmune thrombocytopenia

Question 5

hemolytic disease of the newborn

Answer 5

• Rh factor incompatibility
• of concern only after the first pregnancy
• mortality rate of 50% without intervention (disease targets developing RBC in the fetus)
• prophylactic injection of anti-Rh Abs (RhoGAM)- makes Rh+ blood unrecognizable to the mother’s immune system

Question 6

neonatal alloimmune thrombocytopenia

Answer 6

• thrombocytopenia- low levels of thrombocytes (platelets)
• like HDN only with platelets
• up to 60% of cases occur during the first pregnancy
• mortality of 10% (intracranial bleeds, brain damage, death)
• usually resolves in 2-3 weeks without treatment (involving maternal IgG, which degrades over time)

Question 7

transient neonatal alloimmunity caused by maternal autoimmune disease

Answer 7

1) maternal Abs cross the placenta (type II hypersensitivity since cellular components cannot cross the placenta)
2) bind maternal Ags in fetus
3) elicit an immune response in the fetus (effects are usually transient; rarely are lethal)
- can occur if mother has lupus, myasthenia gravis, graves disease

Question 8

transfusion reactions

Answer 8

• no MHC proteins
• antibodies (IgG) against blood group antigens (ABO blood group antigens, RH blood group antigens)
• agglutination and lysis of RBCs (blockage of blood vessels= ischemia)
• perform cross-matching to prevent

Question 9

ABO incompatibility is type ____ hypersensitivity;

_____ lysis of transfused RBCs

Answer 9

II;

complement-mediated

Question 10

transplantation

Answer 10

intentional transfer of cells, tissues, or organs from one site to another

Question 11

autologous

Answer 11

self-transplant

Question 12

syngeneic

Answer 12

between identical twins

Question 13

allogenic

Answer 13

between individuals of the same species

Question 14

xenogenic

Answer 14

between species

Question 15

organ transplant criteria

Answer 15

• irreversible organ damage
• no alternative treatment options
• non-recurring disease
• transplant compatibility

Question 16

most important HLA to match

Answer 16

HLA-DR (class II molecule)

Question 17

minor HLA differences

Answer 17

• associated proteins from the donor with different amino acid sequences
• encoded by genes outside the HLA regions
• not detected by standard tissue typing techniques
• can cause graft rejection in up to one third of transplants

Question 18

transplant rejection is primarily ____ mediated

Answer 18

cell

Question 19

transplant rejection is classified according to _____

Answer 19

time

Question 20

causes of transplant rejection

Answer 20

• donor class I MHC molecules
• donor class II MHC molecules
• ABO molecules
• endothelial antigens (vascular tissue)
• minor HLA

Question 21

hyperacute transplant rejection

Answer 21

• occurs within minutes of transplantation
• pre-existing host serum Abs specific for alloantigens
• Ag-Ab complex settles in the donated tissue activating plasma protein systems (complement, etc.) and leukocyte infiltration –> massive blood clots in the capillaries of the transplanted tissue –> ischemia- “white graft”
• preventable with careful ABO and HLA matching

Question 22

acute transplant rejection

Answer 22

• mismatched HLA and MHC antigens
• within the first few weeks to months to a year
• leads to activation of T cells
• cell-mediated (most common) or humoral destruction of the graft
• two ways:
• donor APC activate recipient T-cells
• PAPC in recipient can recognize alloantigens in graft and mount adaptive immune response to produce antibodies

Question 23

acute transplant rejection:

T-cell mediated reactions

Answer 23

• usually occurs within days of transplantation
• directed at the MHC molecules on DONOR APCs
• severe infiltration of the graft by macrophages
• can be minimized/prevented via immunosuppressant drugs
• damage to endothelial cells of the donor is reason for rejection

Question 24

acute transplant rejection:

antibody-mediated rejection

Answer 24

• more rare
• occurs within days of transplantation-1 to 2 weeks out
• Ab against graft HLA-antigens
• B-cells activated
• activate complement
• accumulation of Ab, complement, neutrophils= clotting in the donor blood vessel

Question 25

chronic rejection

Answer 25

- humoral and cell-mediated response (precise mechanism poorly understood) - proliferation of fibroblasts and vascular cells - slow progressive loss of organ function - most transplants have an element of this that will eventually occur - arteriosclerosis of the donor vessels (thickening due to collagen deposition)

Question 26

Graft vs. Host Disease (GVHD)

Answer 26

- side effect of bone marrow or cord blood transplant - major have been matched - mismatch is between minor HC antigens - donor lymphocytes attack host - treatment: immunosuppressant therapy - clinical manifestations: diarrhea, skin lesions, jaundice, spleen enlargement

Question 27

tolerance

Answer 27

clinical goal of transplantation; host tolerating foreign tissue

Question 28

immunosuppressive drugs

Answer 28

- allow for imperfect matches - important in controlling the MHC antigen rejection - prevent acute rejection (take in advance of surgery) - lack specificity and durability (dampens appropriate immune responses)

Question 29

corneal transplant (penetrating keratoplasty)

Answer 29

- 5 year success rate of ~90% - optical (scarring) - reconstructive (corneal ectasias, thinning) - therapeutic (recurrent infection: herpes) - cosmetic (non-seeing eye)

Question 30

immune privilege

Answer 30

- "hidden" from immune system - isolation from a vascular supply - isolation from a lymphatic supply - presence of a vascular barrier (blood barriers) - active suppression (anterior chamber associated immune deviation) - no dendritic cells in the central cornea

Question 31

corneal graft rejection

Answer 31

- key risk factor: corneal vascularization - acute (< 4 weeks, cytotoxic T-cell mediated) - chronic (usually progressive, non-responsive to therapy) - corneal edema, rejection line (of immune cells), vascularization

Question 32

future of transplantation

Answer 32

- xenotransplantation - induction of tolerance - regenerative medicine - artificial organs