Alloimmunity Flashcards
alloimmunity
immune response to genetically dissimilar tissue
transient neonatal immunity- 2 causes
- fetal Ag/maternal Ab
- maternal autoimmune disease
transient neonatal immunity caused by fetal Ag/maternal Ab
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
2 types of transient neonatal immunity caused by fetal Ag/maternal Ab
- hemolytic disease of the newborn
- neonatal alloimmune thrombocytopenia
hemolytic disease of the newborn
- 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
neonatal alloimmune thrombocytopenia
- 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)
transient neonatal alloimmunity caused by maternal autoimmune disease
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
transfusion reactions
- 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
ABO incompatibility is type ____ hypersensitivity;
_____ lysis of transfused RBCs
II;
complement-mediated
transplantation
intentional transfer of cells, tissues, or organs from one site to another
autologous
self-transplant
syngeneic
between identical twins
allogenic
between individuals of the same species
xenogenic
between species
organ transplant criteria
- irreversible organ damage
- no alternative treatment options
- non-recurring disease
- transplant compatibility
most important HLA to match
HLA-DR (class II molecule)
minor HLA differences
- 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
transplant rejection is primarily ____ mediated
cell
transplant rejection is classified according to _____
time
causes of transplant rejection
- donor class I MHC molecules
- donor class II MHC molecules
- ABO molecules
- endothelial antigens (vascular tissue)
- minor HLA
hyperacute transplant rejection
- 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
acute transplant rejection
- 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
acute transplant rejection:
T-cell mediated reactions
- 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
acute transplant rejection:
antibody-mediated rejection
- 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
chronic rejection
- 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)
Graft vs. Host Disease (GVHD)
- 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
tolerance
clinical goal of transplantation; host tolerating foreign tissue
immunosuppressive drugs
- 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)
corneal transplant (penetrating keratoplasty)
- 5 year success rate of ~90%
- optical (scarring)
- reconstructive (corneal ectasias, thinning)
- therapeutic (recurrent infection: herpes)
- cosmetic (non-seeing eye)
immune privilege
- “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
corneal graft rejection
- 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
future of transplantation
- xenotransplantation
- induction of tolerance
- regenerative medicine
- artificial organs
