Transplant Immunology Flashcards
(26 cards)
autograft
graft from same host
syngeneic graft
between two genetically identical individuals
allograft
graft from donor of same species but genetically unlike
xenograft
between individuals of different species
graft vs host disease
when transplanting bone marrow, you run the risk of the immuno-competent cells in the graft attacking the host
what antigens in the graft are most commonly the targets of immune mediated rejection and why
MHCs. there appears to be a large number (2-10%) of lymphocytes programmed against foriegn MHC complexes, and this causes rejection
the difficulty in finding donor “matches” is that there is so much MHC polymorphism
minor H antigens
many genetic loci code for minor histocompatibility antigens, which can elicit smaller responses over time, but are poorly understood
describe priviledged sites w/ respect to graft immunity
some locations are difficult for the immune system to see, and so rejection is not a concern in these places
- anterior eye
- brain
- fetus
what cells are most responsible for rejection?
T-cells, specifically CD4
describe the difference between direct and indirect allorecognition
direct- TCR binds directly to foreign MHC and elicits
T cell activation regardless of the peptide on the MHC
indirect- TCR recognizes peptide derived from the foreign MHC that is cross presented by normal host APCs on normal host MHCs
which MHC is more important when considering matches?
MHC2- b/c response is mediated by CD4
hyperacute rejection
occurs w/in minutes or hours, mediated by preexising Ab in the donor. usually the donor has some prior exposure to these antigens via blood transfusions, transplants, etc.
ex. ABO blood types
acute rejection
occurs within weeks or months- activated lymphocytes and monocytes. mostly mediated through CTLs, helpterT cells, and monocytes/macrophages
controlled by immunosuppressive drugs
chronic rejection
gradual loss of function of graft over months to years. mechanism unclear.
IgM deposits seen in arterial walls and t-cell infiltration also seen
not controlled by immunosuppressive drugs
how is host/donor compatability assessed beforehand?
HLA typing to identify MHC sequences
bone marrow transplant
grafting of stem cells into host d/t cancers of blood or bone marrow. BMT recipients immune system destroyed prior to transplantation, but infection and GVH disease remain major threats
what are the immunosuppresion techniques?
- drugs
- radiation
- ablation
- biologic agents (anti-CD20, anti-CD3)
tolerance vs immunosuprression
tolerance is the depression of an immune response towards a specific antigen
immunosuppression is generalized suppression of the immune system
cyclosporin A
fungal antibiotic that inhibit T cell proliferation and differentiation w/o significant B cell effects
Tacrolimus
immunosuppressive drug for kidney, heart and liver transplants
corticosteroids
inhibit T cell homing, decrease response of macrophages decrease monocyte count, inhibit IL2
in general- major affect on cell mediated immunity
azathioprine
blocks nucleic acid synthesis and decreases cell replication. inhibits T and NK cells ADCC
cyclophosphamide
prevents S phase in proliferating B cells. highly toxic, carcinogenic, etc
irradition
causes lymphocyte death in a dose dependent manner
