Immunodeficiencies II: Primary Deficiencies of Adaptive Immunity Flashcards
review pg 2
2
defect in x linked hyper IgM is not defect in B cell, defect is
CD40L mutation or deletion that compromises B cell/T cell interaction
humoral immunodeficiency can be caused by
b cell defect or t cell defect
intrinsic to b cell humora immunodeficiency:
XLA Selective IgA deficiency CVID Immunoglobulin IgG subclass deficiencies Transient hypogammaglobulinemia of infancy
X linked agammaglobulinemia (XLA0 is also known as
bruton’s agammaglobulinemia
CVID stands for
common variable immunodeficiency
intrinsic to t cell humoral immunodeficiency:
X-linked hyper-IgM syndrome
draw out antibodies and infants graph
pg 6
neonate is protected at birtha nd for 6 months by passively transferred
IgG from mother
what is the only isotype that can cross placenta
IgG
at time of birth baby has what levels of IgG
adult levels (of its moms IgG)
first immunoglobulin that the baby will make
IgM
at birth the baby starts to make its own
IgG
before birth baby makes what Ig?
M and A
features of pts with b cell deficiencies
recurrent respiratory infections and streptoccemia
organisms that predominate infections for b cell deficienceis:
Streptococci, Staphylococci and Haemophilus spp.
vast majority of viral infections are controlled how well through individuals with no b cell
pretty well - t cell will take care of on its own pretty well
infants with primary immunodeficiencies will not present with symptoms before
6-9 motnhs b/c they whave moms IgG
agammaglobulinema means
deficiency in ability to make antibodies
when does XLA present
6-8 months
common to have pneumonia by 2-3 yo. and recurrent upper respiratory tract infections that may never completely resolve and may have measles and be able to get rid of it, in what disease
XLA
why do XLA pts not have tonsils
tonsil are greater than 90% b cells, so no b cells, no tonsils
why does XLA not have lymphadenopathy
no folicles expanding into secondary and germinal centers, so no enlareged lymph nodes
serum levels for pt with XLA
IgM not detectable
IgA and IgG low
tonxilar node of pt with XLA
no b cells so just connective tissue
flow cytommetry of pt with XLA
no b cells so no CD19 marker pg 14
XHIGM is due to defect in
t cell
defect in XHIGM is in
CD40L
XHIGM stands for
X-linked Hyper-IgM
CD40L is also known as
CD154
MOI for XHIGM
x linked recessive
activation of macrophages will be defective in XHIGM why
b/c the Cd40/40L is needed for activation of macrophages
neutropenia is sign of
XHIGM
neutropenia is probably due to what in XHIGM
neutrophils exhausted, they are doing so much work b/c they don’t have IgG to help them out so they exhaust themselves faster
all fungal infections require
cell mediated response
pts with XHIGM are risk for getting
Recurrent upper and lower respiratory infections with bacteria, Pneumocystis jiroveci, CMV, Cryptococcus
fungi cannot be controlled
cluse to XHIGm
boy with hypogammaglobulinemia wit low or absent IgG and IgA with normal or elevated IgM
what is treatment for XHIGM
IGIV and anti-fungals
no live virus vaccines
bone marrow transplanation
why would somebody with deficiecny in CD40L not have follicels or germinal centers
consequence of first t cell b cell interaction - it will not happen without CD40/CD40L interaction so no proliferating b cells os no follicular follicles or germinal centers
what is whole purpose of germinal center reaction
somatic hypermutation to increase affinity of antibody
what would happen in CD40L deficiency in regards to somatic hypermutation
little to none, the first interaction depdent on CD40L is not going to happen
review pg 18
18
CD40L only expressed on T cells after
activation - and then transiently
t ells have to be ____ to express CD40L
activated
CD25 is a marker of
activated t cells
CD25 is
alpha chain of IL-2 receptor
it converts IL-2 to high affinity IL2
how do you know t cells are activated when you do flow cytometry
look for CD25 b/c it is marker of activated t cells
review pg 19
19
lymph node with hyper-IgM vs. not
no germinal centers in pt with hyper-IgM
autosomal form of hyper-IgM is usually caused by
AID deficiency
AID is required for
class switching
defect in function of AID causes
most common autosomal recessive form of hyper-IgM syndrom
HIGM2 is
autosomal recessive form of Hyper-IgM syndrom with lack of AID
AID satnds for
Activation-Induced Cytidine Deaminase
three major abnormalities characterized by AID deficiency:
- lack of immunoglobulin somatic hypermutations
- the absence of immunoglobulin class switch recombination
- lymph node hyperplasia caused by the presence of giant germinal centers.
HIGM2 from x linked - what are they distinguished by
HIGM2 has giant germinal centers
why does HIGM2 have giant germinal centers?
it will have the first b cell t cell interaction and they proliferate like crazy. there is no defect in CD40L here so b cells will go into follicel and proliferate, but they can’t mtuate the rearranged VJ or VDJ so no b cell has advantage over the other, they won’t increase affinty so nobody is outcompeting, so you get giant follicles
in the x linked version they won’t proliferate
selective IgA deficiency is
The severe deficiency or total absence of IgA both serum and secretory IgA.
what is most common of primary immunodeficiency
selective IgA deficiency
majority of individuals with selective IgA deficiency defect is unknown but there are genes associated
:)
b lymphocytes appear normal in selective IgA deficiency but do not
mature into IgA producing plasma cells
selective IgA deficiency most common in indviiduals with
european descent
how does one get selective IgA deficiency
familial, can also be acquired by measles or viral infection
what is weak in selective IgA deficiency
Mucosal defenses weakened; infections in respiratory, GI, urogenital tracts common.
how do pts with selective IgA deficiency present
Asymptomatic to symptomatic: patients present with recurrent sinopulmonary infections and diarrhea
NOTECARD PG 23
23
CVID stands for
Common Variable Immunodeficiency
CVID is:
CVID is a disorder characterized by low levels of serum immunoglobulins and increased susceptibility to chronic, recurrent sinopulmonary infections. Relatively “common” and degree and type of deficiency is “variable” from patient to patient.
unlike other primary Ig deficiencies the presentation of CVID is frequently
much later in life - early adulthood (most others present as babies)
treatment of pts with CVID
antibiotics, intravenous IG
B cell numbers in CVID
normal
T cells in CVID
normal
B cells are normal in CVID but
they decrease with time
the genetic defects in CVID all involve
roles in b cell and plasma cell survival and isotype switch
individuals with CVID have decreased wht in b cells
decreased isotyped switching and decreased memory cells for b cells
why do you get IgG levels at all (or any Ig) with XLA?
depends on how bad the mutation is and how inactivating that mutation is
XLA is what MOI
x linked recessive
male or female more likely to get XLA
male
peripheral blood lymphocytes from female carriers show skewed, or non random x chromosome inactivation, why?
it’s not really non-random in the b cell lineage - any b cell that has inactivated the x chrom that has the functional BTK is not going to make it through b ccell development, so the only ones that make it htrough the periphery in carriers are the ones that have inactivated the x chrom that carriers the effective allele. so it looks like non-random x chrom activation - during b cell development it’s not random - its chosen b/c they are the only ones that will make it
if mutation is totally inactiativating in XLA what will youdetect in serum
no b cells and no Ig
what is the marker of B cells
CD19
CD19+ is a marker of
b cells
flow cytommetry to look for CD19+ cells in pts with XLA you won’t find them in individuals where:
tyrosine kinase mutation is totally inactivating
where is block in b cell maturation in XLA
pre-b cell stage
what are t cell levels in pt with XLA
normal
should pts with XLA receive live vaccines
no
when will pts with XLA show symptoms
once mothers igG is below protective threshold
draw out b cell maturation in bone marrow
pg 10
need stem cell factor binding to what in b cell maturation in bone marrow
ckit
what does IL-7 need to bind to in b cell maturation in bone marrow
IL-7R
what is required for rearrangement in b cell
RAG1 and RAG2
RSS
Tdt
what does Tdt add
N nucleotides
block in b cell development in XLA is at
pre b cell stage
pre B cell receptor is
IgM (mu heavy chain) with surrogate light chain
to get beyond pre b cell receptor you need to do what
tell the cell that the pre b cell receptor works
signaling through the pre b cell receptor is dependent on
BTK
BTK stands for
bruton’s tyrosine kinase (what is mutated in XLA)
why can the cell not go beyond pre b cell in XLA
the BTK is mutated and that is what is needed to tell the cell that the pre b cell receptor works
consequences of signaling through the pre b cell receptor
exclude further rearrangement at heavy chain - allelic exlcusion
proliferation to make most of heavy chain you have
generate light chain - initaite VJ to join
the signaling part associated with the b cell receptor is
Igbeta and Igalpha ad ITAM
what is the CD for Igbeta
CD79b
what is the CD for Igalpha
CD79a
what besdies Btk can be defective/mutated in autosomal recessive forms of agamaglobinemia
mutations in Igalpa or Igbeta
lambda 5 - component of surrogate light chain
review pg 12, female non random x chrom inactivation for XLA
12
in female carrier of XLA if you sample serum, the only b cells you will find have:
they are the ones that silenced the defective BTK so only the working BTK cells will be expressed in the periphery, the other ones wouldn’t make it out
deficiency in one or two IgG sublcasses where other immunoglobulin levels are normal and suffer recurrent infection is what deficiency
selective IgG subclass
Selective IgG Subclass Deficiency is less severe than
XLA & CVID
predominant IgG sublcass
IgG1
IgG2 deficiency is common in
children
IgG3 deficiency is common in
adults
ppl deffecicent in IgG4 often also deficient in
IgG2
deficiency of IgG1 comomon in
trick - not common, it is rare
family members with IgG subclass deficiency can also have
selective IgA deficiency or CVID
diagnosis of Selective IgG Subclass Deficiency
History of recurrent infections of ears, sinuses, bronchi and /or lungs.
Low level for age of IgG subclass and normal levels of other immunoglobulins.
Normal numbers of B and T cells
Normal function: DTH and lymphocyte stimulation
IgG2 subclass deficiency: unable to produce antibodies when immunized with polysaccharide vaccines
Some children outgrow IgG subclass deficiency
treatment of selective IgG sublcass def.
antibiotics for infections or prophylactically
what is level of IgG sublcass for IgG subclass deficiency
low level for age
what is level of Ig besides IgG in IgG subclass deficeincy
normal
IgG2 dominates the response against
capsular polysaccharides
if there is IgG2 subclass deficiency, what is the major reason why this is bad
they can’t produce antibodies when immunized with polysaccharide vaccines
most dominant IgG
1
least dominant IgG
4
what IgG take longest to reach adult levels
IgG2 and 4
IgG1 and 3 are most efficeicnt to
activate complement - most efficient is 3
IgG2 can compensate for
1 and 3, can fill in for response to conjugate polysaccharide vaccine
x linked agammaglobulinemia - genotype? phenotyep?
bruton’s tyrosin kinase, no b cells
x linked hyper IgM, genotype and phenotype?
CD40L mutated no class switch, no germinal centers
AR hyper IgM genotype and phenotype?
AID, no class switch, giant germinal centers
x linked and AR hyper IgM feature
No somatic hypermutation
selective IgA deficiency, genotype and phenotype?
defect unknown, can have anti-IgA
CVID, genotype and phenotype?
various defects (unknown majority)_, adolescent and older onset (20-30s)
selective IgG sublass defieicny, genotype & phenotype?
defect unknown, usually discovered inadvertently
review pg 32
32
vast majority of cases of t cell defieincy, will also impact
b cell function
what is almost always imapcted by t cell deficiency
cell mediated and humoral
defects in CD4 T cell development can result in
severe combined immunodeficiencies b/c then they can’t help b cell, so impact antibody production. b cell non functional b/c no help from t cell
SCID - impact in purine salvage pathway results in
toxic metabolites
if you cannot signal from t cell receptor, t cells cannot become activated, so then they cannot
provide help to b cells
defects in antigen receptor gene rearrangemnt can result in
SCID
genetic defect in thymic function that block t cell development result in
seere immunodeficiencies
complete absence of thymus is very
rare - there is usually some thymic tissue
repeated viral or fungal infections suggests what disorder
t cell
JAk 3 deficiency results in failrue to signal through
interluekin receptors (2 & 7) interluekin signal through JAK STAT pathway
omenn syndrome results in mutations from
VDJ recombination - usually RAG 1 or RAG2
Omenn syndrome b cell and t cells tend to be
autoreactive
describe RAG1 and RAG2 ain omenn syndrome
usuallyk have some function
mutations in TAP1 and TAP2 give rise to what syndrome
MHC class I defieicny
why do mutation sin TAP1 & 2 result in MHC1 def.
don’t get peptide binding to class I
MHC1 deficiency is calls
bare lymphocyte syndrome 1
BLS stands for
Bare Lymphocyte Syndrome (BLS) Type I
in BLS there is no
MHC class I
most common mutations in BLS
TAP1 and TAP2
abnormality in BLS?
no CD8 T cells
MHC I what won’t be able to respond
CD8 T cells
need mHC I in thymus to allow
cells to be selected that can bind to MHCI
review endogenous pathway, MHC I, positive selection< CD8 T cells
block 2 ppt 6 pg 39
BLS1 doesn’t really present with
increased susceptibility - they have cytotoxic t cell function - they are cytotoxic CD4 t cells
cytotoxic t cells kill
virlly infected cells
through release of performin & granzymes & slower fas ligand patway
how do cytotoxic t cells kill
release perforin & granzymes
in absence of CD4 t cell will get
SCID
increased susceptibility to what in CD4 deficiency
all pathogens
failure to express MHC II results in what disease
Bare Lymphocyte Syndrome Type II (BLS Type II)
where are most mutations in MHC II for BLS type II
class II transactivatory and regulatory factor X genes
failure to make MHC II results in failure to
failure to select CD4 t cells
without CD4 t cells, you are not going to have
Ig
BLS II is form of
SCID
review exogenous pathway, HC II, positive selection, CD4 t cell
previous blocks yay
CD4 t cells required for what kind of immunityt
cell mediated & humoral immunity
SCIDS stands for
Severe Combined Immunodeficiency Syndromes (SCIDS)
most common form of SCID
x linked recessive form
withotu common gamma chain cannot signal through
any interleukin receptor
what is really important receptor for t cell
IL-7 R
x linked SCID is caused by what deficiency
common gamma chain def.
CD45 gives rise to SCID, why?
need CD45 during t cell activation it activates SRC family kinases, it dephosphorylates them and activates them
IL-7 alpha gives rise to SCID, why?
IL-7 to IL-7R required for t cell development
artemis gene is component of gives rise to SCID, why?
VDJ recombinaze
RAG1 or 2 mutation gives rise to SCID, why?
don’t have RAG1 or 2 can’t rearrange antien receptors, no b or t cells
CD3 delta chain def. gives rise to SCID, why?
can’t signal through t cell receptor
CD3 mutations will impact what
T cell with phenotype similar to XLA in b cell compartment -b/c CD3 is not just signaling of t cell, ,it is also of pre-TCR so no functional CD3 will not make it past pre-T stage
Jak3 def. gives rise to SCID, why?
phenotype similar to def. of IL-7R alpha chain b/c JAK3 associated with IL receptors
most common form of autosomal forms of SCID is
def. in ADA (adneosine deaminase)
autosomal recessive SCID are due to
ADA or PNP deficiencies
ADA is
Adenosine deaminase
PNP is
Purine Nucleoside Phosphorylase
what do all SCID have in common
impact more than one leukcyte lineage b/c they impact function of CD4 T cells rare and often fatal often have a rash lymphopenia (reduced lymphocytes) no cell mediated immune response no humoral immune response lymph node hypoplasia (few or small lymphocytes) treatment: bone marrow transplant
review pg 46
46
you do have b cells in x linked SCID but they are
non functional in absence of t cell help
ADA is required for converstion of
pg 50
ADA def. is what form of SCID
AR
what causes SCID in ADA def.
Accumulation of adenosine, deoxyadenosine, and dATP is toxic for lymphocytes.
T -, B -, NK - , ALL NEGATIVE
what cells do you have in ADA def. form of SCID
T -, B -, NK - , ALL NEGATIVE
what is phenotype of ADA def. form of SCID
T -, B -, NK - , ALL NEGATIVE
PNP def. not as severe as
ADA
PNP def. not as severe as ADA why
it is not as toxic
ataxia is
unstable gait/difficulty walking
mutation in JAK3, what is phenotype
T-, B+ SCID
CD45 def what is phenotype
T-, B+ SCID
IL-7Ralpha def. what is phenotype
T-, B+ SCID
CD3 gamma or CD3 epsiolon def. what is phenotype
T-, B+ SCID
IL-7 is required for
VDJ joining
CD45 is expressed on what
all WBC (leukocytes)
without common gama chain you cannot signal through
IL-4, IL-7, IL-9, IL-15 and IL-21 receptors.
x linked scid phenotype
T-, B+, NK-
review pg 56, describe x linked SCID
56
why can you not look at T cells on X linked SCID
there are none
IL-2 induces proliferation of
B cells
Th1 induces what IL
IL-2
non-random inactivatio nof x chrom in carrier’s b/c
only t cells that have inactivated non fxl one will get to periphery
all SCID will present with what opportunistic infection
thrush (candida alibcans)
XHIGM does not arise due to mutation intrinsic to b cell lineage, mutation is in
t cell lineage - CD40L
defects in CD4 T cell development can result in
SCID
mutations that impact CD4T will present as
SCID
BLS2 due to mutations in
TF required for expression of MHC II alpha dn beta chains - so not class II on surface so no selection for CD4 T cells
most common form of SCID
x-SCID
XSCID due to mutation of
signaling chain of IL-2 - common gamma
individuals with x linked scid fail to develop
t cells
they do develop b cells but they are non functional
IL-2Ralpha chain deletion will inhibit
T cell development in thymus
ADA-SCID and PNP-SCID if they are deficienct can lead to buildup of
adoxyadenosine in ADA and guanine in PNP
ADA and PNP normally expressed in
other cells that can detoxify them. lymphocytes can’t detoxify them. the metabolic bi-products are toxic to lymphocytes
ADA scid differes from x linked scid b/c the individuas are
t cell - and b cell -
no t or b cells
if there are defects in signaling in t cell antigen receptor it will cause
SCID
CD3 required for signaling from
pre t cell receptor and t cell receptor
if CD3 non functional will not pass
pre t cell stage
mutation of CD3 is kind of like equivalent of
XLA, b/c you are stuck in pre b cell in XLA and stuck in pre t cell in CD3 mutation
how does defect of CD45 impact TCR transduction
enzymes needed for phosphorylation of ITAMs are maintained by phosphate, the phosphate is removed by CD45. so can’t get to next step without active CD45
JAK3 more associated with signaling through what receptors
cytokine receptors
alpha chain of IL-2R also known as
CD25
JAK3 kinase is associated with
IL-2R gamma o the common gamma chain
if common gamam chain is ther but can’t signal through it might have what deficiency
JAK3
what is phenotype of JAK defeciency
T-, B+, NK – same phenotype as X-linked SCID
IL 7 binding to IL-7R in thymus does what
opens up t cell thymus receptor loci for rearrangemnt
without signaling through IL-7 won’t get
T cell rearrangement
common gamma chain what is CD
cD132
phenotype of X linked scid and jak scid, what isi the difference in presentation
presentation similar but x linked only males
jak is AR males and females
mutations in RAG-1, RAG-2, artemis could be what syndrome
omenn syndrome
RAG-1, RAG-2 and artemis usually don’t knowck out function of genes, there is usually
still some t cells and b cells developing
mutation sin RAG1, RAG2, artemis are components of
VDJ recominase
omenn syndrom eresults from mutations where
rag1, rag2, artemis
omenn syndrome is also sometimes referred to as
Familial reticuloendotheliosis with eosinophilia
or SCID with hypereosinophilia
omenn has high levels of
eosinophils
what is hallmark of omenn syndrome
high levels of eosinohpils
in indivudlas with omenn, defect in t cell devlopment in thymus leads to
abnormal development of medllary thymis epithelial cells and low expression of AIRE (don’t know why it happens)
don’t get enough presentation of antigens in thymic medulla
poore negative selection in omenn b/c
low expression of AIRE
why do omenn syndrom also rpesent with autoimmune disease
/c of low aire expression so t cells that get through can be autoreactive
in add’n to poor negative selection, aire is also required for
t reg
omenn has less t reg b/c of lack of aire, which also contributes to
autoimmune disease
VDJ recombinase require
RAG-1, RAG-2, Tdt, Artemis
RAG1 and RAG2 determine
what will recombne together - 12 23 rule
what does artemis do
opens the hairpin
withotu functional RAG1 and RAG2 will not get
VDJ recombination
without functional artemis will not get
VDJ recombination
2% of lymphocytes are in blood the rest are in
secondary lymphoid tissue
more t cells or b cells in peripheral blood
t cells
how does omenn syndrome present
rash due to type 1 hypersensitivity response b/c of elevated IGE
what will you find in blood test for omenn syndrome
elevated eosinophils and IgE (so there has to be b cells)
low lymphocytes and neutrophils
decreased t cells
No b clls detected in peripheral bloood (But they are there just not detected)
mostly oligoclonal CD4+ cells (small number of t cell clones)
no thymic shadow
failure to develop thymus give rse to
SCID
Classic thymic function defect
DiGeorge syndrome
complete DiGeorge is extremely
rare
definition f DiGeorge syndrome
Definition: a primary immunodeficiency caused by abnormal development of fetal cells and tissues of the neck (parts of face, brain, thymus, parathyroid glands, heart and aorta).
immune defiict of DiGeorge is due to
hypoplasia or aplasia of thymus
due to effects on parathyroid pts with DiGeorge syndrome pts will often have
neonatal hypocalcemia
if there is thymic aplasia increased susceptiblity to
infection due to deficit of t cells
what beside thymus is affected by digeorge syndrome
cardiac defects
what is MOI for digeorge syndrome
AD
most digeroge resuts from what deletion
22q11
depending on deletion in digeorge determiens
severity of disease - might have just a little hypoplasia of thymus
how can digeorge syndrome present
Highly variable expression of the following:
Chest x-ray may reveal lack of thymic shadow.
T cell responses absent or severely diminished.
Low numbers of circulating T cells (CD3+).
Recurrent or chronic infection with viral, bacterial fungal or protozoal organisms (chronic runny nose, recurrent pneumonia including PCP, thrush, and diarrhea).
Most have normal B-cell immunity, but some have low immunoglobulin levels and fail to make specific antibodies following vaccination.
Treatment: thymic transplant for patients with ‘complete DiGeorge Syndrome’
(pg 70)
if there is impact on t cel development in digeorge there will be
chronic infection with what t cells are involved with:viral, bacterial, fungal or protozoal organisms
if t cell development severly impacted pts with digeorge will present with
opportunistic infections like thrush, pneumonia
thymic aplasia what is treatment for digeorge
thymic transplant
look at thymic shadow vs. non in digeorge
pg 71
review pg 73
73
deficiency in IFN gamma receptor
The normal pathways for host defense against intracellular bacteria are pinpointed by genetic deficiencies of IFN- and IL-12 and their receptors.
IFN gamma important for
controlling intracellular bacterial infections (like TB and leprae)
defects in IFN gamma receptor or one chain of IL-12 are susceptible to what
intracellular bacterial infections & fungal infections
XLP stands for
X-linked lymphoproliferative syndrome
XLP what is impacted?
secretory killing phathway of lymphocytes.
stimulated to proliferate in unctorlled manner so proliferative aspect of disease, susceptiblity to increased viral infections b/c they can’t effectively kill virally infected cells
Hemophagocytic lymphohistiocytosis is characterized by? (part of XLP)
activated macrophages engulfing RBC
what kind of virus often causes problems with XLP
epstein-barr virus
where is defect in XLP
SH2D1A
in absence of SLAM associated protein do not get efficient
differentiatoin into cytotoxic t cells - which are main cells that control EBV infection
what are main cells to control EBV infection
cytotoxic t cells
WAS stands for
Wiskott-Aldrich Syndrome
AT stands for
Ataxia-Telangiectasia
gene mtuated in WAS
WASP
WASP important for
reorganization of cytoskeleton, esp for t cells b/c they have to reorganize their cytoskeleton to help other cells
cytoskeletal reoganization required for
migration
impaired chemotaxis of phagocytes in
WAS
AT mutation that impact
double stranded DNA repair
enzymes of double stranded DNA repair in AT are invovled in
VDJ recombination
WAS classically presents with “classic triad”:
thrombocytopenia
severe eczema (by one year of age)
recurrent pyogenic infections, bloody diarrhea
recurrent pyogenic infections due to what in WAS
inability o ft cell to provide help to b cell to opsonize bacteria
severe eczema in WAS due to
hypersensitivity response - they ahve elevated levels of IgE
why do pts with WAS have high IgE
do’nt know :(
b/c t cells cannot provide help to b cells in WAS suseptibility to infections by
encapsulated bacteria
treatment for WAS
BMT
what is mOI for WASP
x linked recessive
female carriers of WAS exhibit
skewe or non-random x chrom. inactivation
Where is WASp expressed
all white blood cells and megakaryocytes
what is the HSR in excema for WAS
tyep I HSR
gene impacted in AT
ATM gene
main features of AT
unstable gait (ataxia) dilation of vessels in eye recurrent infections (respiratory and sinus)
unusual feature of AT is:
strongly associated with IgA deficiency
what kind of deficiency is very common in pts with AT
IgA def.
high rate of what disease in pts with AT
leukemia & lymphoma
what is MOI for AT
AR
most individuals with AT have elevated serum levels of
alpha fetoprotein
what is serum test tosee if pt has AT
alpha fetoprotein
what is often test to see if pt has AT
radiation - they are very suseptible to breaks in chrom. due to radiation
BLS 1 impacts class I expression where
all cells on body (MHC 1 is everywhere)
review pg 84
84
review pg 85
85
review pg 86
86
