Unit 5 Flashcards
What is HLA
human leukocyte antigen
polymorphic glycoproteins on surface of cells
What chromosome contains the human MHC
p arm / short arm of chromosome 6
Match Class I, class II and class III with their ___
DP, DR,DQ glycoproteins
A, B, C glycoproteins
complement and TNF
D- class II
ABC- class I
complement- class III
regions on chromosome 6 that contain genes for MHC (LOCI)
What are the 4 fields in HLA nomenclature
1- protein/ allele group
2- specific allele variants
3- synonymous DNA substitutions/ silent mutations and exons
4- non-coding regions- introns and UTRs
Are there more HLA class I genes or class II
class I- more than 20,000
class II- less than 7000
What type of inheritance do HLA genes tend to have
codominant
one haplotype from mom
one haplotype from dad
What is linkage disequilibrium and does it occur in HLA inheritance
when haplotypes occur at unexpected frequencies, yes it does
deviates from the hardy winburg principle
Name what class the following genes are from?
A1
B8
DR17
A1 and B8 class I
DR17 class II
What are the parts of the HLA class I protein
3 alpha chains and 1 B2 macroglobulin
2 alpha and 2 beta chains
What kind of cells have an HLA class I? and HLA class II?
all nucleated cells
antigen presenting cells
What is the source of antigens being screened by HLA class I?
And class II?
endogenous
exogenous
What part of the Ig chain does HLA class I code for?
and class II?
both for heavy chains of class I or II glycoproteins
When does a patient need HLA typing and abs
if they are getting a solid organ transplant, BM transplant, graft transplants
What is an allogenic BM? and an auto
when a pt receives BM from someone else
auto- when a pt receives their own
BM back
What elements must match for a BM transplant to be compatible
pt HLA abs must match donor lymphsq
How is HLA tested for transfusions with the CDC method
complement deficiency cytotoxicity assays are done to test pt serum against donor lymphs and reagent complement to see if compliment activates. AHG is also added as enhancement
How is flow cytometry used to test HLA
donor lymphs isolated by T and B cells, incubated with pt serum, if HLA is present it will react toward the pt lymphs
What is engraftment monitoring and how does it work
monitors signs of GvHD
identifies short tandom repeats STRs between donor and pt
practice slide 26`
slide 26
What do each of these terms mean
autologous
syngenic
allogenic
xenogenix
GvHD
HvGD
syn-twin donation
xeno-other species
What cells and what class can leav to GvHD and HvGD
T cells- class I
ab responses- class II
NK- class I
compliment
Which is worse, GvHD or HvGdg
GvHD
What kind of recognition do each of these cells do
T cell
Ab
NK
T cell- direct
Ab indirect
NK allorecognition
What cells mediate HvGD in hyper acute, acute or chronic phases
hyper acute- preexisting Abs - min to hours- complement activated
acute- CD4 and CD8 - 2 weeks to 1 month
chronic- CD4 and B cell responses
What might cause a hyper acute HvGD
previous transplants or transfusions, multiple pregnancies
What are the effects of acute HvGD
vascular damage due to leukocytes attack
inflammation
tissue necrosis
ab mediated respons
What can cause GvHD
BM, thymus, spleen, blood transfusion in neonate
What are the effects of acute GvHD
endothelial tissue damage, death to skin, liver, gastrointestinal tract
rash, jaundice
What cells are activated in acute GvHD
mature T cells in the graft
What are the effects of chronic GvHD
gradual ab and slow rejection
organ damage, scar formation on organs, fibrosis and atrophy of organ
How is GvHD treated? How to prevent it?
immunosuppression and steroids
HLA testing prior to transplant
Describe the parts of direct allo recognition? and indirect?
direct-patient T helper CD4 attaches to MHC class II on donor APC, acute
indirect- donor cell proteins are presented by APCs of recipient- chronic
How is HLA used for paternity testing
HLA genes from mom and dad are used to see if child matches these
What genetic markers are analyzed in paternity testing
RBC, HLA, enzymes, proteins
What are 1st and 2nd order exclusions
1st- gene in child that is not in mom nor dad
2nd- gene not in child that is in dad
practice slide 44, 46
slide 44
first order or 2nd
What does hydrops fetalis mean
edema in fetus
What does icterus gravis mean
jaundice
What does erythroblastosis fetalis mean
immature RBCs in circulation- related to anemia
What causes the most severe form of HDFN? and the least severe
Rh system
ABO
What are the 3 main causes of HDFN
Rh, ABO, other
What are the 4 conditions that must be met for HDFN to occur
Mom is exposed to foreign antigen from pregnancy
exposed to foreign antigens causing ab production
Ab can cross the placenta (IgG)
infant must have a well developed antigen that mom doesn’t have
What is the function of placenta
O2 exchange, nutrients, waste products
barrier between mom and fetus circulation
Describe fetal blood flow
fetal veins bring oxygenated blood to heart, pumps deoxygenated blood back to placenta via arteries
maternal blood provides nutrients and removes waste
Which HDFN can occur in the first pregnancy as mild
ABO
Which HDFN does not affect the 1st pregnancy, but the second pregnancy can have severe issues
Rh
How can HDFN lead to jaundice, what is this condition called
plasma albumin binds to some bilirubin
if there is too much it will remain unbound, accumulates in CNS
kernicterus
Describe the bilirubin pathway
RBCs lyse and release heme
heme is converted into unconjugated bilirubin
free bilirubin in the bloodstream
albumin conjugates bilirubin in liver,
broken down into urobilinogen in gut
can be excreted in feces or urine
What Rh type of HDFN is most severe
anti-D most common
What antigens cant cause HDFN and why
Lewis, I and P,not well established at birth