Wk 3 Path Lab Allografts Recognition and Rejection Flashcards
What happends w/ rejection?
T lymphocytes and antibodies produced against graft antigens react against and destry tissue grafts
Allografts
Grafts exchanged b/w indiv of same species
Xenografts
Grafts b/w diff species
What are the major antigenic differences b/w donor and recipient?
Differences in HLA alleles
Why are immune responses to allografts stronger than responses to pathogens?
The frequency of T cells that recognize foreign antigens ina graft is much higher than the frequency of T cells specific for any microbe
What, besides T cells, recognize graft antigens?
B cells recognize antigens, including HLA, but activation requires T cells too
What are the classifications for graft rejection?
- hyperacute
- acute
- chronic
What mediates hyperacute rejection?
Preformed antibodies specific for antigens on graft endothelial cells
-can be natural IgM specific for blood group antigens or Abs specific for allogeneic MHC molecules induced by prior exposure
What happens with hyperacute rejection?
Affected kidney becomes rapidly cyanotic, mottled and anuric, acute fibrinoid necrosis -> become nonfunctional and have to be removed
What mediates acute rejection?
T cells and antibodies that are activated by alloantigens in the graft
-w/in days or weeks
What are the 2 types of acute rejection?
- Acute cellular (T cell-mediated) rejection - CD8+ CTLs can directly destroy graft cells or CD4+ cells secrete cytokines and induce inflammation, damaging the graft
- acute antibody-mediated rejection - antibodies bind to vascular endothelium and activate complement via classical pathway -> graft failure
What happens w/ chronic rejection?
= an indolent form of graft damage, occurs over months or years -> progressing loss of graft fxn
-manifest as interstitial fibrosis and gradual narrowing of graft blood vessels
Which organs benefit from polymorphic HLA matching?
Kidney
Why isn’t HLA matching done in organs like the liver, heart and lungs?
Other considerations take precedence: anatomic compatibility, illness severity, storage time
What immunosuppressive drugs are currently used?
- steroids (decrease inflammation)
- mycophenolate mofetil (inhibits lymphocyte proliferation)
- tacrolimus (inhibits phosphatase calcineurin - reqd to activate NFAT, which stimulates cytokine gene transcription)
- T cell & B cell-depleting antibodies
- IVIG
- Plasmapheresis in severe Ab-mediated rejection
