Immunodeficiencies I: Primary Deficiencies of Innate Immunity Flashcards
(124 cards)
1
Q
it’s very unusual to see a t cell def. that doesn’t also present as
A
combined immunodeficiency
2
Q
primary immune deficiency, most molecular defects are
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known
3
Q
if someone has history of repeated infections, suggest diagnosis of
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immunodeficiency
4
Q
primary immunodeficiency are generally caused by
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inherited gene defect
5
Q
immunodeficiency disease only treatable by
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Hematopoietic stem cell transplantation or gene therapy can be useful to correct genetic defects.
6
Q
primary immunodeficiency are very
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rare
7
Q
secondary immunodefieicncies are very
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common - major cause of infection and death
8
Q
pure Immunodeficiencies
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like x linked amanoglobinemia
clinical presentation is pretty similar
9
Q
complex Immunodeficiencies
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clinical presentation varies a lot
10
Q
signifiance of Immunodeficiencies
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increased risk of opportunistic infections and tumors
11
Q
what are more common, primary or secondary Immunodeficiencies
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secondary
12
Q
primray or secondary can result in lesionsoutside of immune system
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secondary Immunodeficiencies
13
Q
X linked SCID is example of
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inherited primary Immunodeficiencies
14
Q
in SCID pt does not have
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T cells
15
Q
polymorphisms in primary Immunodeficiencies are much more common than
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the mutations that give rise to the primary Immunodeficiencies
16
Q
three causes of primary Immunodeficiencies
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mutations
polymorphisms
polygenic disorders
17
Q
selective IgA def. is most common of
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primary Immunodeficiencies
18
Q
notecard pg 8
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8 - only do the ones he has gone through
19
Q
asplenia is very
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rare
20
Q
APCEd defieicney in
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AIRE
21
Q
IPEX deficiency in
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FOXP3
22
Q
name some things that would cause you to suspect Immunodeficiencies
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family history of it need IV antibodiotics or hospitalization to clear infection 2 or more infections of pneumonia per year 2 or more sepsis or meningitis recurrent or resistant candidiasis recurrent tissue or organ absecesses infection w/ opportunistic organism live vaccine complications non-healing wounds, chronic diarrhea
23
Q
review pg 13
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13
24
Q
if there are recurrent infectiosn indictation there may be problem with
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complement, phagocytes, or immunoglobulins
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recurrent viral/fungal/opportunisitic infections may be problem with
T cell (cell mediated)
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bacterial infections are
extracellular
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intracellular pathogens are
intracellular
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defects in phagocytes permit
widespread bacterial infections
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defects in complement permit
widespread bacterial infections
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LAD stands for
leukocyte adhesion deficiency
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LAD1 prevents
adhesion ofphagocytes to actiated endothelium
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LAD2
leukoctyes cannot adhere to endothelium
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LAD3
defect in CD15, no rolling
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all LAD result in neutrophils :
they can't get to site of infection
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CGD stands for
chronic granulomatous disease
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CGD results in mutation in
NADPH oxidase complex
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if you can't assemple NADPH you lack
oxidative pathway
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what is morst important killing of phagocytes
oxidative pathway
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clinical effect of CGD
chronic bacterial and fungal infections
| granulomas
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CHS stands for
chediak higashi syndrome
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defect in CHS
lysosomal trafficking regulator protein
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functional effect in CHS
defective fusion of endosomes and lysosomes
| defective phagocytosis
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clinical effect of CHS
recurrenta nd presistant bacterial infections
granulomas
damage organs
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how would you diagnose Immunodeficiencies
complete blood count/differential
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if you find abnormal neutrophil counts what will you then look at
CD11/CD18 assay
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LAD results in profound
leukocytosis
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leukocytosis
electaed leukocyte numbers in peripheral blood
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LAD1 defect?
defect in beta chin ofintegrin
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beta chain is present where
LFA-1
| CR3 CR4
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CR3 and 4 are involve din
complement -b ind to opsinized bacteria
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review pg 20, draw out the effect LAD on leukocyte adhesion cascade
pg 20
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will pts with LAD gorm pus
no
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when does LAD present
1-2 months of age
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LAD is characterized by extreme
leukocytosis
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why is LAD characterized by extreme leukocytosis
they can't get through endothelium to site of infection
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what happens very early on to signal LAD
Umbilical Cord - Delayed separation at birth, postnatal redness and swelling (omphalitis)
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describe Rebuck skin window
mild abrasion on skin and cover slip applied, abrasion of skin induces mild inflamatory response so neutrophils are attracted. normal individuals: neutrophils will attach to cover slip. individuals with LAD, no neutrophil attachment
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flow cytometry for LAD
to analyze fi pt has it
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treatment for LAD
BMT
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BMT stands for
bone marrow transplantation
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CD15 is
sialyl lewis
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draw out flow cytometry of normal individual compared to CD18 and CD15
pg 23
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draw out flow cytometry of pt with LAD II
pg 23
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draw out flow cytometry of pt with LAD I
pg 23
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what is defective step in LAD II
rolling
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what step is defective in LAD I
tight binding step
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NBT test looks at
ability of neutrophils to kill what they have inside them
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CGD are compromised in
oxidative killing pathways
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most common mutation in CGD
gp91
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gp91 is encoded on
x chromosome
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catalase breaks down
hydrogen peroxide
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in absence of hydrogen peroxide, if pacteria are catalase negative there will still be
some to make superoxide anion
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symptoms of CGD
recurrent infections with catalase-positive bacteria, fungi (normal flora)
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susceptible infections of CGD
extracellular pathogens and fungi (neutrophils)
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to test CGD/functionality of NADPH oxidase
NBT test
| flow cytometry
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NBT test assess
assess function of NADPH oxidase
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negative NBT indictivei of
defective NADPH oxidase
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if neutrophils are functional they reudce
NBT and blue crystals of reduced NBT
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NBT stands for
Nitro Blue Tetrazolium
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DHR stands for
Dihydrorhodamine
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DHR test, describe
flow cytometry - resting neutrophils will not reduce the DHR
82
if you expose the neutrophils from healthy individuals to formil ester then the activated neutrophils will (IN DHR TEST)
reduce DHR - increased fluerescence
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individuals with CGD, when you expose them to formil ester they do not
reduce DHR - non-functional
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what woudl you see in carrier of CGD on DHR?
review pg 27
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CHS results from
mutation in lysosomal trafficking regulator gene, LYST
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lysosomal traficking is impaired in CHS so ther will be
giant granules in lysosomes
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what else is impaired besides lysosomal trafficking in CHS
impaired chemotaxis, and abnormal NK cell activity
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symptosm of CHS besides impaired chemotaxis, and abnormal NK cell activity
albinism, neurological abnormalities
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LAD1 deficient in
CD18
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LAD2 deficient in
CD15
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CGD defect in
NADPH oxidase
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most common form of CGD is
x linked
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CHS results in mutation f what gene
LYST
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LYST controls
trafficking of lysosomes
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A50 tests for
alternative pathway activity
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CH50 tests for
deficiencies in the classic pathway by measuring the ability of the patient's serum to lyse antibody-coated sheep erythrocytes.
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review my complement pathway thing
:D see also his pg 31
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can soluble be opsinized by complement
no
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deficiencies in components of early classical pathway lead to increase susceptibility of
immune-complex disease
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defects in alternative pathway
C3b which is required for opsinization of pathogens so susceptibility of
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why not imune compleex disease if you're not generating C3d
you still have c4b
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what is most serious deficieny oc fomplenet
C3
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deficiency of C3 leads to susceptibility of
encapsulated bacteria
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without C5-9 can't generate
MAC
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no C5-9 you are susceptible to
Neisseria
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Neisseria meningitidtis is
encapsulated
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Neisseria gonorrhoeae is
not encapsulated
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DAF and CD59 are anchored to
membrane
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neisseria species handeled by
MAC
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most people with neisseria disease have what form
encapsulated - so neisseria meningiditis
111
deficiency in enzyme PIGA means that
DAF and CD59 cannot be anchored to membrane
112
what does PIGA do
makes the GPi anchor to anchor DAF and CD59 to the membrane
113
what does DAF do
displaces c2a from c4b (dissociation of c3 convertase)
114
in absence of membrane associated DAF and CD59 we will get
complement activation on cell surface
115
if we have deficiency of DAF and CD59 what disease do we get
Paroxysmal Nocturnal Hemoglobinuria (hemoglobin in urine)
116
CD55 is
DAF
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DAF stands for
decay accelerating factor
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CD59 is
protectin & HRF
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C1 inhibitor deficiency gives rise to what disease
Hereditary Angioedema (HAE)
120
most people with HAE have what type
type I
121
HAE type I is classified by
low serum levels of normal C1-INH
| so C1 inhibitor is not defective but there isn't enough of it
122
HAE type II is classifeid by
normal level of C1 inhibitor but it is not functional
123
function of C1 inhibitor
displaces c1r and c1s from c1
displaces masp 1 and masp2 from MBL or ficolins
important in kinin and coagulation cascade
124
why do you have edema in HAE
c1 inhibitor isn't functioning well and it is important in kinin cascade, like braadykinin, so you get fluid into tissues
