15) Transplantation & tumors Flashcards
autograft
same individual
no imm response
isograft
genetically identical individual
no imm response
allograft
genetically dissimilar individual
imm rejection
xenograft
different species
imm rejection
2 types of allograft rejections (1st/2nd exposure)
- first set rejection – original transplant rejection
- second set rejection – second transplant from same donor; imm memory
in vitro Ab that can block transplant Ags from T-cells to enhance graft survival
enhancing antibodies
evidence for immunologic nature of rejection
- lymphs/monos found at site
- those lacking T-cells do not reject
- rejection slows in immunosuppressed
- specific T-cells and Ab formed against graft
- enhancing antibodies function
3 types of graft rejection
- hyperacute
- acute
- chronic
rejection in minutes to hours
preformed Ab to graft
hyperacute rejection
complement activated
swelling, thrombosis
fever
leukocytosis
little/no urine production
hyperacute rejection
rejection after a few days
no previous sensitization
acute rejection
—— rejection may be reduced by immunosuppressive drugs
acute
rejection months after transplant
both Ab and cell-mediated
chronic rejection
major region of immunologic importance for transplantation
MHC
graft rejection begins with…
activation of CD4+ T-cells by non-self MHCII on graft
CD8+ may be activated by MHCI
lymphs of donor and recipient reacted with panel of Ab
lymphocytotoxicity test
can detect donor/recipient differences to a single AA
genotyping
leukocytes from donor and recipient cultured together for several days and T-cells with radioactively labelled DNA proliferate if incompatible
mixed leukocyte reaction
stabilize lysosomal membranes
inhibit T-cell cytokine production
induce lysis of lymphs
anti-inflammatories
(corticosteroids)
interfere with RNA/DNA synthesis
anti-metabolites
monoclonal Ab (OKT3) given before, during and after transplant; specific for lymphs
cytotoxic/blocking agents
interferes with cytokine gene transcription in T-cells
even allows transplant between unmatched donor/recipient
nephrotoxic
cyclosporine
similar to cyclosporine, not as nephrotoxic
FK506
induces total immunosuppression prior to transplant
total lymphoid irradiation
helps protect fetus against rejection by mother
alpha-fetoprotein
Ag on malignant cells not present on normal cells
tumor specific ag
Ag “hidden” on normal cells or “overexpressed” on tumor cells
tumor associated ag
categories of tumor ag
- chemically or physically induced – harder to tx, not cross reactive
- virally induced – cross reactivity
- oncodevelopmental antigens – expressed on normal embryo/fetus, not on normal adults
- antigens of spontaneous tumors – unknown causes
CEA and AFP are examples of…
oncodevelopmental ags
IgG and IgM are ineffective against —– tumors
large, solid
parts of cell-mediated tumor defense
- cytotoxic T-cells
- NK cells
- lymphokine activated killer cells (LAKs)
how tumors escape imm system
- privileged sites (lens of eye)
- antigenic modulation
- blocking by soluble Ag released by tumor
- tumor-specific suppressor T-cells
- prostaglandins released by tumors
- large tumor mass
elevated in liver cancer, cirrhosis, hepatitis
AFP
normally present in GI tract, but not blood except in malignancy or inflammatory disease
CEA
