Wed 2 - Nelson - Transplant pathology and amyloidosis Flashcards
What is meant by
isograft
allograft
xenograft
o Isograft = syngeneic, between identical twins
o Allograft = between genetically different individuals of the same species
o Xenograft = between two species, ex. pig (porcine) heart valve to human
Other names for MHC I and II
I - HLA-a/b/c
II - HLA-DR
what is the major antigenic difference between donor and recipient that results in rejection of transplant
differences in the highly pleomorphic HLA alleles
direct and indirect pathways of CELLS responding to donor alloantigens
direct:
CD4+ proliferate & produce CKs (IFN-γ) - tissue damage by a local delayed hypersensitivity reaction
CD8+ T cells responding to graft antigens differentiate into CTLs that kill graft cells
Indirect pathway:
graft antigens are picked up, processed, and displayed by host APCs and activate CD4+ T
cells, which damage the graft by a local delayed hypersensitivity reaction and stimulate B cells to produce Ab
what happens if preformed antibodies respond to an alloantigen
where can these come from
hyperacute rejection
pregnancy, previous transfusion, previous transplant
Hyper acute rejection
two reasons it can happen
ABO
or
anti HLA preformed antibody
missmatch
results in complement activation
acute rejection to graft
why it happens
CD4 t cells release CKLs, which activate macrophages, CD8s and B cells to attack the graft
chronic rejection
occurs over months to years often secondary to vascular injury as a result of cell and antibody mediated responses
most common cause of renal graft failure
HCT
two types
hematopoietic cell transplantation
autologous HCT - uses self hematopoietic progenitor cells - cannot get GVHD
allogeniccells from someone else - transplanted t cells from donor may attack host - GVHD
acute GVHD
first 100 days
direct cytotox by CD8 graft t cells
CK released from CD4 graft t cells
Sx dermatitis, destruction of bile duct = jaundice, GI uncer, bloody diarrhea
Chronic GVHD
> 100 days after
can have loss of appendages, dermal fibrosis
chronic liver disease = cholestatic jaundice
diarrhea, fibrous structures in GI tract
obliterative bronchiolitis
Amyloidosis
what is the tertiary structure of the proteins
linear, non branching fibrils in cross-beta-pleated sheet configuration.
amyloidosis
h and e stain
other stains?
amorphous, eosinophilic hyaline
congo red -> pink - red deposits
yellow green with polarizing microscope
AL amyloidosis
AKA primary amyloidosis - most common
amyloid light chain: complete Ig light chains, fragments of light chains, or both
produced by a monoclonal population of plasma cells (5-15% of Multiple myeloma patients get AL amyloidosis -> monoclonal (lambda or kappa - bence-jones protein) free in serum light chain protein
AA amyloid
Amyloid - associated amyloid AKA reactive systemic amyloidosis.
derived by proteolysis of a larger precursor protein in serum called SAA (serum amyloid-associated) protein that is synthesized in liver & circulates in serum associated w/ high density lipoprotein
SECONDARY to chronic inflammatory condition (like RA)
A(beta) amyloid
derived by proteolysis of a larger precursor protein = amyloid precursor protein
Found in the cerebral plaques and walls of cerebral vessels of patients with Alzheimer DZ
Transthyretin
normal serum protein that binds and transports thyroxine and retinol
mutations result in amyloid
AKA heritable neuropathic/cardiomyopathic amyloidosis
sometimes seens as deposits in heart
Beta2 microglobulin
o β2-microglobulin: normal serum protein cannot be filtered through dialysis membranes and can accumulate in patients
on long term dialysis (>20 years) = hemodialysis-associated amyloidosis
Cause of age related systemic amyloidosis
amyloid deposition with wild type TTR (transthyretin) protein
how do you Dx amyloidosis
tissue biopsy with staining for amyloid
