Robbin's: Transplant Rejection Flashcards
Rejection of allografts is largely due to
MHC molecules–> very polymorphic
define allograft
same species–> not genetically identical
define xenograft
diff. secies–>not genetically identical
define syngeneic
same species–> genetically identical
define autograft (isograft)
your ass skin to your arm
two main mechanisms for which the host immune system responds to MHC molecules on the graft
Direct recognition
indirect recognition
Define direct recognition
Host T cells rectly recognize MHC molecules on Graft DC’s bound to any antigen (cross reaction)
>If it is HLA A or B–> CTL activation–>kill the graft
> If it is HLA DR–> Cd4–> cytokines (IFNgamma)–>damage and delayed type hypersensitivity
HLA genes involved in direct recognition
HLA A, B, DR
Graft DC’s with MHC molecules bound to any antigen is thought to mimic…
Self MHC molecules bound to foreign antigen
Define indirect activation
host CD4Tcells recognize antigen on MHC molecules only AFTER it has been picked up by the hosts own APC’s
>t cells specific for donor antigens acitvate B cells and antibodies are formed against the donor tissue
major differences in Direct Vs Indirect path
direct= No B cell involvement or production of anti-donor Ab’s
indirect–> sampling of alloantigen after the peptides have been taken up by cell’s own APC’s where in direct itsTcells interacting with donor APC’s (DC’S)
T cell mediated rejection takes 3 forms..
- CTL’s kill graft cells
- CD4 t cells release inflammatory cytokines resulting in graft damage (similar to a DTH reaction)
- Activated macrophages (via IFN gamma) can injure graft vasculature
*ischemia and graft rejection is the result
Ab mediated rejection MOA
Allogenic antibodies bind to graft endothelium and cause vascular injury by activation of compliment and activation of leukocytes.
Hyperacute rejection MOA
PREFORMED anti-donor anti-bodies against graft tissue
and also mis-matched blood type/tissue type for which there would already be pre-formed ab’s
hyperacute time frame
minutes to hours
How can Hyperacute rejection happen
> blood type mismatch
individual was exposed to forgein HLA from a prior blood transfusion
multiparous women who have anti-HLA ab’s against paternal HLA encountered during preganacy
previous transplant rejection
Time frame of acute rejection
days or weeks in a non-immunosuppressed host
histo findings of cellular acute rejection
*occurs within the first months and presents as renal failure
mononuclear infiltrate (CD4 and CD8) DESTROYS PARENCHYMA (AND VESSELS) BY CYTOTOXICITY AND INFLAMMATORY REACTIONS
histo findings of humoral acute rejection
vasculitis
CNI with renal toxicity
cyclosporin
how to distinguish from renal failure and renal Cyclosprin toxicity
renal biopsy
Acute humoral injection is also known as
rejection vasculitis
Acute humoral rejection path findings
vsculitis with endothelial cell necrosis, neutrophillic infiltration, deposition of antbody, compliment and fibrin and thrombosis
*ISCHEMIC NECROSIS OF RENAL PARENCHYMA
know what happens in chronic rejection
IDGAF
HSC’s are infused where following chemo/readiation
Peripheral Blood–>they then hone to their blood cells nicihes
rejection of HSC’s is carried out by which cell types
T cells and NK cells that are resistant to chemo/radiaton
GVHD occurs when…
immunologically competent t cells are given to a pt. who is immunocompromised
Graft cells recognize host cells as foreign and attack host cells
Mismathches associated with GVHD
MINOR histocompatability complexes
organs with lots of lymphoid cells (liver)
non-irradiated whole blood
ACUTE GVHD (days/weeks) attacks epithelial cells in what three target organs
Skin–> macropapular skin rash
Gut–> diarrhea
Liver–> high serum biliirubin
Chronic GVHD manifestation
skin lesions simila to SS with other findings of various autoimmune diseases
