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Microbiology - Transplantation
pgs 206 - 210
17
Microbiology
Professional
10/04/2010

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Term
syngeneic
Definition
identical genetic constitution (inbreds or identical twins)
Term
allogeneic
Definition
differing genetic constitution, btwn members of the same species

not identical twins
Term
xenogeneic
Definition
major genetic differences between different species
Term
autograft
Definition
tissue grafted BACK to the original donor
Term
isograft
Definition
tissue grafted btwn syngeneic individuals

btwn identical twins, inbreds.. etc
Term
allograft
Definition
tissue grafted btwn allogeneic individuals
Term
xenograft
Definition
tissue grafted btwn xenogeneic individuals

ape to a man
Term
Major Histocompatibility Complex
Definition
closely linked family of polymorphic genes which encode for cell surface histocompatibility antigens

responsible for transplant rejection reactions btwn genetically dissimilar individuals
Term
allograft rejection (host-versus-graft reaction)
Definition
host immune system attacks graft

kinetics of rejection determined by degree of genetic difference btwn HLA, quantity of tissue engrafted, type of tissue engrafted, immune status of recipient, and previous exposure of recipient to graft

has three phases of rejection
1. recognition phase
2. proliferation and differentiation phase
3. destruction phase
Term
describe three phases involved in allograft rejection
Definition
RECOGNITION PHASE - graft antigens taken up and displayed in host APCs; antigen reactive lymphs become activated

PROLIFERATION PHASE - CD4+ T cells and/or macs mediate the induction of proliferation and differentiation of effector cell precursors

DESTRUCTION PHASE - activated CTLs are primary destructive force; perforins and granzyme expression; activated B cells --> PCs --> anti-graft Abs --> complement mediated lysis and release of chemoattractant/vasoactive complement components
Term
destruction phase of allograft rejection
Definition
activated CTLs are primary destructive force; perforins and granzyme expression; activated B cells --> PCs --> anti-graft Abs --> complement mediated lysis and release of chemoattractant/vasoactive complement components
Term
tissue matching
Definition
identification of cell surface antigens (HLA) to match donor with recipient

class I antigens - HLA-A, B, C
class II antigens - HLA-DP, DQ, DR

tissue typing - used to determine the EXACT collection of HLA antigens expressed by graft donors/recipient

performed with panels of MONOCLONAL ANTIBODIES reactive with individual HLA antigens

alternatively, PCR techniques can be used to identify HLA antigens at the gene level

MINOR HISTOCOMPATIBILITY ANTIGEN is not taken into consideration in tissue matching and thus may be responsible for graft rejection observed in matches involving same HLAs
Term
tissue-typing
Definition
used to determine the EXACT collection of HLA antigens expressed by graft donors/recipient

performed with panels of MONOCLONAL ANTIBODIES reactive with individual HLA antigens

alternatively, PCR techniques can be used to identify HLA antigens at the gene level

MINOR HISTOCOMPATIBILITY ANTIGEN is not taken into consideration in tissue matching and thus may be responsible for graft rejection observed in matches involving same HLAs
Term
mixed leukocyte culture (MLC) test
Definition
mimics proliferation phase of graft rejection by measuring stimulation of recipients CD4+ T cells against alloreactive donor cells

primary antigenic targets in the test are class II (HLA-D) alloantigens found mainly on B cells or macs

class I antigens may serve as secondary stimuli
Term
describe the MLC culture technique
Definition
1. Cells to be tested for alloreactivity = RESPONDER CELLS; cells to be tested as the TARGETS of potential alloreactivity = STIMULATOR CELLS

2. make reaction ONE-WAY by giving stimulator cells a lethal dose of irradiation or mitomycin C (DNA synthesis inhibitor)

3. Mix and incubate all cells for several days at 37 *C in presence of radio-isotope-labeled DNA synthetic precursors (H-TdR); this determines the rate of cell division/proliferation which reflects intensity of activation of the responder cells
Term
describe final step in MLC culture technique.. why is H-thymidine (H-TdR) important?
Definition
Mix and incubate all cells for several days at 37 *C in presence of radio-isotope-labeled DNA synthetic precursors (H-TdR)

H-TdR helps us determine the rate of cell division/proliferation

this info reflects intensity of activation of the responder cells
Term
graft versus host disease (GVHD)
Definition
graft immune system attack the recipient's

1. ACTIVATION of donor cells - primary manifestations are the result of activation of large numbers of CD4+ T cells and their production of infla cytokines

resulting symptoms - think TRIAD
Epidermitis (mononuclear infiltration of skin)
Hepatitis (infiltrate hepatic bile ducts)
Entericitis (sloughing intestinal mucosa)
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