what are the major HLA loci examined when HLA matching?

• HLA-A (MHC I)
• HLA-B (MHC I)
• HLA-DR (MHC II)

these are the most important/diverse loci 

what accounts for the massive and strong T cell response to donor MHC alleles?

there is a high frequency of "primed" or reactive T cells (~2-10%) that react to the MHC molecules of donor allografts

MUCH higher freq than a T cell for another Ag never seen before (<.01%)

what are the pathways of T cell recognition of alloantigens?

• direct: T cells recognize donor MHC bound-Ag on donor derived APC (intact allogeneic MHC molecule)
• indirect: alloAg presented on host APC post-processing of alloAg; a T cell specific for polymorphic peptide from allogeneic MHC molecule binds

what donor cell population is crucial to initiating the graft rejection response?

the "passenger leukocytes" in the donor tissue, particularly donor intraepithelial DCs

these cells express MHC class I/II molecules as well as AMPLE costimulatory molecules (CD40,B7) which is an alloAg that is recognized as such by T cells...thus starting the rejection process (this would be the direct pathway)

just like the adaptive immune response, graft immunity has what 2 key features?

• memory (demonstrated in second set response that is accelerated and strong)
• specificity

when is tissue typing used and why is not used in all organ transplant cases?

HLA tissue typing is used in kidney transplantation

not used for other organs (heart, lung, liver) because the potential ischemic damage (functional damage via fibrosis) outweighs the potential benefit of a good HLA match; plus likelihood of a full 6 HLA histocompatibility match is low with so few available organs

• blood group typing (ABO compat.)
• cross match to identify (and EXCLUDE) pre-formed recipient Abs against donor
• wait list priority taken into account
  • organ size
  • geographic proximity
  • clinical urgency
  • prognosis/survival likelihood
• tissue typing in case of kidney transplant

memory T cells that have already seen the alloAgs that the present donor presents to recipient T cells

this situation is avoided through screening for reactivity prior to graft

cell mediated response with T cells, macrophages; also some Abs involved

this reaction is treatable with immune suppression

not fully known

number of theories: T cell mediated w/ or w/o Ab?

absence of self-MHC (NK)?

late consequence of initial injury?

• primary lesions in vascular endothelium and graft parenchyma (fibrosis) with loss of normal structure
• chronic DTH reaction in vessel wall
• intimal smooth muscle cell proliferation
• vessel occlusion
• more likely to occur after acute rejection but again mechanisms are poorly understood

why is xenotransplantation from pig to human currently difficult?

porcine cells have a carbohydrate: Gal 1,3 a-Gal sugar that decorates many porcine proteins & that react strongly with Anti-Gal IgM

this sugar is a target for immunotherapy: GalTKO (knock out the enzyme req'd for the production of Gal 1, 3 Gala)