Wed 2 - Nelson - Transplant pathology and amyloidosis

Question 1

What is meant by

isograft
allograft
xenograft

Answer 1

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

Question 2

Other names for MHC I and II

Answer 2

I - HLA-a/b/c

II - HLA-DR

Question 3

what is the major antigenic difference between donor and recipient that results in rejection of transplant

Answer 3

differences in the highly pleomorphic HLA alleles

Question 4

direct and indirect pathways of CELLS responding to donor alloantigens

Answer 4

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

Question 5

what happens if preformed antibodies respond to an alloantigen

where can these come from

Answer 5

hyperacute rejection

pregnancy, previous transfusion, previous transplant

Question 6

Hyper acute rejection

two reasons it can happen

Answer 6

ABO

or

anti HLA preformed antibody

missmatch

results in complement activation

Question 7

acute rejection to graft

why it happens

Answer 7

CD4 t cells release CKLs, which activate macrophages, CD8s and B cells to attack the graft

Question 8

chronic rejection

Answer 8

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

Question 9

HCT

two types

Answer 9

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

Question 10

acute GVHD

Answer 10

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

Question 11

Chronic GVHD

Answer 11

> 100 days after

can have loss of appendages, dermal fibrosis

chronic liver disease = cholestatic jaundice

diarrhea, fibrous structures in GI tract

obliterative bronchiolitis

Question 12

Amyloidosis

what is the tertiary structure of the proteins

Answer 12

linear, non branching fibrils in cross-beta-pleated sheet configuration.

Question 13

amyloidosis

h and e stain
other stains?

Answer 13

amorphous, eosinophilic hyaline

congo red -> pink - red deposits

yellow green with polarizing microscope

Question 14

AL amyloidosis

Answer 14

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

Question 15

AA amyloid

Answer 15

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)

Question 16

A(beta) amyloid

Answer 16

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

Question 17

Transthyretin

Answer 17

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

Question 18

Beta2 microglobulin

Answer 18

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

Question 19

Cause of age related systemic amyloidosis

Answer 19

amyloid deposition with wild type TTR (transthyretin) protein

Question 20

how do you Dx amyloidosis

Answer 20

tissue biopsy with staining for amyloid