Transplantation Flashcards
what types of hypersensitivity reactions can be triggered by transplantation?
Type II (antibody), Type III (immune complex), Type IV (delayed)
graft v host is a type ___ hypersensitivity
type IV (delayed)
peaks 48 to 72 hours
commonly seen in bone marrow transplants, present with diarrhea/rash/jaundice
autotransplanation vs xenotransplantation vs allotransplantation
auto = self-derived
xeno = from another species
allo = from another human
hyperacute transplantation rejection
antibody-mediated (Type II hypersensitivity - IgM or IgG), due to pre-formed circulating antibodies
immediate reaction - minutes to hours (organ will become mottled)
what are the 2 main methods for HLA (MHC) crossmatching?
Cytotoxic Assay: combine recipient serum + donor lymphocyte + complement (if antibodies are present, complement will lyse cells - positive crossmatch)
flow Cytometry: combine recipient serum + donor lymphocyte + fluorescent labeled antibodies against human IgG
describe the direct and indirect pathway by which recipient cells recognize allograft antigens
direct: graft APC present antigens, direct CTL cytotoxicity (CD8 mediated, CD4 activated as well but not as strongly)
indirect: recipient APC present antigens, activate antibodies (CD4+ Th1 mediated)
what happens in delayed antibody-mediated transplant rejection?
antibody to donor (generally to HLA) form following transplantation —> trigger classical complement pathway
clinical effect: delayed graft function
pathology: vascular inflammation (monocytes), leukocytes, thrombosis, tissue injury
in antibody mediated rejection, inflammation is within vessels. positive staining for ____ in vasculature indicates complement activation
C4d (complement protein)
clinical and biochemical signs of acute T-cell mediated transplant rejection in
a. kidney
b. heart
c. lungs
a. kidney - increased BUN/creatinine, proteinuria, decreased urine output
b. heart - decreased ejection fraction
c. lungs - dyspnea, drop in lung function
occurs weeks-months following transplant (or cessation of anti-rejection medication)
manifests as T-lymphocyte infiltrate of organ tissue (histologically)
how are T cells primed to injure an allograft transplantation?
the direct pathway of allograft presentation - APC in graft induce reaction that is heavily CTL mediated
how does acute T-cell mediated transplant rejection appear histologically?
abundant T cell infiltrate into tissue
what manifests from the following forms of transplant rejection:
a. hyperacute antibody mediated
b. antibody mediated
c. acute cellular rejection
d. chronic rejection
a. hyperacute antibody mediated: pre-formed antibodies cause ischemic necrosis (<48 hours)
b. antibody mediated: antibodies activate classical pathway of complement (C4d is good marker)
c. acute cellular rejection: infiltrating CTL (CD8+) attack via MHC I
d. chronic rejection: fibrosis due to progressive arteriosclerosis
acute GVHD is caused by [type of immune response] and presents with [symptoms]
occurs during first 100 days
CD8+ T cell-mediated toxicity
usually manifests in epithelium, liver, GI (rash, jaundice, diarrhea)
chronic GVHD
usually follows acute GVHD but can present insidiously (acute may not have been noticeable)
severe inflammation with fibrosis - skin, liver (cholestasis), intestine (strictures), lungs
immunodeficiency due to thymus destruction, autoimmune syndromes
how can GVHD be prevented?
deplete donor T cells prior to infusion (virtually eliminates risk)
*however - increased leukemia relapse, graft failure, and EBV-lymphomas
or photophoresis (treat WBC with UV)
