Immunodeficiencies II: Primary Deficiencies of Adaptive Immunity Flashcards Preview

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Flashcards in Immunodeficiencies II: Primary Deficiencies of Adaptive Immunity Deck (312)
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1
Q

review pg 2

A

2

2
Q

defect in x linked hyper IgM is not defect in B cell, defect is

A

CD40L mutation or deletion that compromises B cell/T cell interaction

3
Q

humoral immunodeficiency can be caused by

A

b cell defect or t cell defect

4
Q

intrinsic to b cell humora immunodeficiency:

A
XLA
Selective IgA deficiency
CVID
Immunoglobulin IgG subclass deficiencies
Transient hypogammaglobulinemia of infancy
5
Q

X linked agammaglobulinemia (XLA0 is also known as

A

bruton’s agammaglobulinemia

6
Q

CVID stands for

A

common variable immunodeficiency

7
Q

intrinsic to t cell humoral immunodeficiency:

A

X-linked hyper-IgM syndrome

8
Q

draw out antibodies and infants graph

A

pg 6

9
Q

neonate is protected at birtha nd for 6 months by passively transferred

A

IgG from mother

10
Q

what is the only isotype that can cross placenta

A

IgG

11
Q

at time of birth baby has what levels of IgG

A

adult levels (of its moms IgG)

12
Q

first immunoglobulin that the baby will make

A

IgM

13
Q

at birth the baby starts to make its own

A

IgG

14
Q

before birth baby makes what Ig?

A

M and A

15
Q

features of pts with b cell deficiencies

A

recurrent respiratory infections and streptoccemia

16
Q

organisms that predominate infections for b cell deficienceis:

A

Streptococci, Staphylococci and Haemophilus spp.

17
Q

vast majority of viral infections are controlled how well through individuals with no b cell

A

pretty well - t cell will take care of on its own pretty well

18
Q

infants with primary immunodeficiencies will not present with symptoms before

A

6-9 motnhs b/c they whave moms IgG

19
Q

agammaglobulinema means

A

deficiency in ability to make antibodies

20
Q

when does XLA present

A

6-8 months

21
Q

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

A

XLA

22
Q

why do XLA pts not have tonsils

A

tonsil are greater than 90% b cells, so no b cells, no tonsils

23
Q

why does XLA not have lymphadenopathy

A

no folicles expanding into secondary and germinal centers, so no enlareged lymph nodes

24
Q

serum levels for pt with XLA

A

IgM not detectable

IgA and IgG low

25
Q

tonxilar node of pt with XLA

A

no b cells so just connective tissue

26
Q

flow cytommetry of pt with XLA

A

no b cells so no CD19 marker pg 14

27
Q

XHIGM is due to defect in

A

t cell

28
Q

defect in XHIGM is in

A

CD40L

29
Q

XHIGM stands for

A

X-linked Hyper-IgM

30
Q

CD40L is also known as

A

CD154

31
Q

MOI for XHIGM

A

x linked recessive

32
Q

activation of macrophages will be defective in XHIGM why

A

b/c the Cd40/40L is needed for activation of macrophages

33
Q

neutropenia is sign of

A

XHIGM

34
Q

neutropenia is probably due to what in XHIGM

A

neutrophils exhausted, they are doing so much work b/c they don’t have IgG to help them out so they exhaust themselves faster

35
Q

all fungal infections require

A

cell mediated response

36
Q

pts with XHIGM are risk for getting

A

Recurrent upper and lower respiratory infections with bacteria, Pneumocystis jiroveci, CMV, Cryptococcus

fungi cannot be controlled

37
Q

cluse to XHIGm

A

boy with hypogammaglobulinemia wit low or absent IgG and IgA with normal or elevated IgM

38
Q

what is treatment for XHIGM

A

IGIV and anti-fungals
no live virus vaccines
bone marrow transplanation

39
Q

why would somebody with deficiecny in CD40L not have follicels or germinal centers

A

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

40
Q

what is whole purpose of germinal center reaction

A

somatic hypermutation to increase affinity of antibody

41
Q

what would happen in CD40L deficiency in regards to somatic hypermutation

A

little to none, the first interaction depdent on CD40L is not going to happen

42
Q

review pg 18

A

18

43
Q

CD40L only expressed on T cells after

A

activation - and then transiently

44
Q

t ells have to be ____ to express CD40L

A

activated

45
Q

CD25 is a marker of

A

activated t cells

46
Q

CD25 is

A

alpha chain of IL-2 receptor

it converts IL-2 to high affinity IL2

47
Q

how do you know t cells are activated when you do flow cytometry

A

look for CD25 b/c it is marker of activated t cells

48
Q

review pg 19

A

19

49
Q

lymph node with hyper-IgM vs. not

A

no germinal centers in pt with hyper-IgM

50
Q

autosomal form of hyper-IgM is usually caused by

A

AID deficiency

51
Q

AID is required for

A

class switching

52
Q

defect in function of AID causes

A

most common autosomal recessive form of hyper-IgM syndrom

53
Q

HIGM2 is

A

autosomal recessive form of Hyper-IgM syndrom with lack of AID

54
Q

AID satnds for

A

Activation-Induced Cytidine Deaminase

55
Q

three major abnormalities characterized by AID deficiency:

A
  1. lack of immunoglobulin somatic hypermutations
  2. the absence of immunoglobulin class switch recombination
  3. lymph node hyperplasia caused by the presence of giant germinal centers.
56
Q

HIGM2 from x linked - what are they distinguished by

A

HIGM2 has giant germinal centers

57
Q

why does HIGM2 have giant germinal centers?

A

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

58
Q

selective IgA deficiency is

A

The severe deficiency or total absence of IgA both serum and secretory IgA.

59
Q

what is most common of primary immunodeficiency

A

selective IgA deficiency

60
Q

majority of individuals with selective IgA deficiency defect is unknown but there are genes associated

A

:)

61
Q

b lymphocytes appear normal in selective IgA deficiency but do not

A

mature into IgA producing plasma cells

62
Q

selective IgA deficiency most common in indviiduals with

A

european descent

63
Q

how does one get selective IgA deficiency

A

familial, can also be acquired by measles or viral infection

64
Q

what is weak in selective IgA deficiency

A

Mucosal defenses weakened; infections in respiratory, GI, urogenital tracts common.

65
Q

how do pts with selective IgA deficiency present

A

Asymptomatic to symptomatic: patients present with recurrent sinopulmonary infections and diarrhea

66
Q

NOTECARD PG 23

A

23

67
Q

CVID stands for

A

Common Variable Immunodeficiency

68
Q

CVID is:

A

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.

69
Q

unlike other primary Ig deficiencies the presentation of CVID is frequently

A

much later in life - early adulthood (most others present as babies)

70
Q

treatment of pts with CVID

A

antibiotics, intravenous IG

71
Q

B cell numbers in CVID

A

normal

72
Q

T cells in CVID

A

normal

73
Q

B cells are normal in CVID but

A

they decrease with time

74
Q

the genetic defects in CVID all involve

A

roles in b cell and plasma cell survival and isotype switch

75
Q

individuals with CVID have decreased wht in b cells

A

decreased isotyped switching and decreased memory cells for b cells

76
Q

why do you get IgG levels at all (or any Ig) with XLA?

A

depends on how bad the mutation is and how inactivating that mutation is

77
Q

XLA is what MOI

A

x linked recessive

78
Q

male or female more likely to get XLA

A

male

79
Q

peripheral blood lymphocytes from female carriers show skewed, or non random x chromosome inactivation, why?

A

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

80
Q

if mutation is totally inactiativating in XLA what will youdetect in serum

A

no b cells and no Ig

81
Q

what is the marker of B cells

A

CD19

82
Q

CD19+ is a marker of

A

b cells

83
Q

flow cytommetry to look for CD19+ cells in pts with XLA you won’t find them in individuals where:

A

tyrosine kinase mutation is totally inactivating

84
Q

where is block in b cell maturation in XLA

A

pre-b cell stage

85
Q

what are t cell levels in pt with XLA

A

normal

86
Q

should pts with XLA receive live vaccines

A

no

87
Q

when will pts with XLA show symptoms

A

once mothers igG is below protective threshold

88
Q

draw out b cell maturation in bone marrow

A

pg 10

89
Q

need stem cell factor binding to what in b cell maturation in bone marrow

A

ckit

90
Q

what does IL-7 need to bind to in b cell maturation in bone marrow

A

IL-7R

91
Q

what is required for rearrangement in b cell

A

RAG1 and RAG2
RSS
Tdt

92
Q

what does Tdt add

A

N nucleotides

93
Q

block in b cell development in XLA is at

A

pre b cell stage

94
Q

pre B cell receptor is

A

IgM (mu heavy chain) with surrogate light chain

95
Q

to get beyond pre b cell receptor you need to do what

A

tell the cell that the pre b cell receptor works

96
Q

signaling through the pre b cell receptor is dependent on

A

BTK

97
Q

BTK stands for

A

bruton’s tyrosine kinase (what is mutated in XLA)

98
Q

why can the cell not go beyond pre b cell in XLA

A

the BTK is mutated and that is what is needed to tell the cell that the pre b cell receptor works

99
Q

consequences of signaling through the pre b cell receptor

A

exclude further rearrangement at heavy chain - allelic exlcusion
proliferation to make most of heavy chain you have
generate light chain - initaite VJ to join

100
Q

the signaling part associated with the b cell receptor is

A

Igbeta and Igalpha ad ITAM

101
Q

what is the CD for Igbeta

A

CD79b

102
Q

what is the CD for Igalpha

A

CD79a

103
Q

what besdies Btk can be defective/mutated in autosomal recessive forms of agamaglobinemia

A

mutations in Igalpa or Igbeta

lambda 5 - component of surrogate light chain

104
Q

review pg 12, female non random x chrom inactivation for XLA

A

12

105
Q

in female carrier of XLA if you sample serum, the only b cells you will find have:

A

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

106
Q

deficiency in one or two IgG sublcasses where other immunoglobulin levels are normal and suffer recurrent infection is what deficiency

A

selective IgG subclass

107
Q

Selective IgG Subclass Deficiency is less severe than

A

XLA & CVID

108
Q

predominant IgG sublcass

A

IgG1

109
Q

IgG2 deficiency is common in

A

children

110
Q

IgG3 deficiency is common in

A

adults

111
Q

ppl deffecicent in IgG4 often also deficient in

A

IgG2

112
Q

deficiency of IgG1 comomon in

A

trick - not common, it is rare

113
Q

family members with IgG subclass deficiency can also have

A

selective IgA deficiency or CVID

114
Q

diagnosis of Selective IgG Subclass Deficiency

A

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

115
Q

treatment of selective IgG sublcass def.

A

antibiotics for infections or prophylactically

116
Q

what is level of IgG sublcass for IgG subclass deficiency

A

low level for age

117
Q

what is level of Ig besides IgG in IgG subclass deficeincy

A

normal

118
Q

IgG2 dominates the response against

A

capsular polysaccharides

119
Q

if there is IgG2 subclass deficiency, what is the major reason why this is bad

A

they can’t produce antibodies when immunized with polysaccharide vaccines

120
Q

most dominant IgG

A

1

121
Q

least dominant IgG

A

4

122
Q

what IgG take longest to reach adult levels

A

IgG2 and 4

123
Q

IgG1 and 3 are most efficeicnt to

A

activate complement - most efficient is 3

124
Q

IgG2 can compensate for

A

1 and 3, can fill in for response to conjugate polysaccharide vaccine

125
Q

x linked agammaglobulinemia - genotype? phenotyep?

A

bruton’s tyrosin kinase, no b cells

126
Q

x linked hyper IgM, genotype and phenotype?

A
CD40L mutated
no class switch, no germinal centers
127
Q

AR hyper IgM genotype and phenotype?

A

AID, no class switch, giant germinal centers

128
Q

x linked and AR hyper IgM feature

A

No somatic hypermutation

129
Q

selective IgA deficiency, genotype and phenotype?

A

defect unknown, can have anti-IgA

130
Q

CVID, genotype and phenotype?

A

various defects (unknown majority)_, adolescent and older onset (20-30s)

131
Q

selective IgG sublass defieicny, genotype & phenotype?

A

defect unknown, usually discovered inadvertently

132
Q

review pg 32

A

32

133
Q

vast majority of cases of t cell defieincy, will also impact

A

b cell function

134
Q

what is almost always imapcted by t cell deficiency

A

cell mediated and humoral

135
Q

defects in CD4 T cell development can result in

A

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

136
Q

SCID - impact in purine salvage pathway results in

A

toxic metabolites

137
Q

if you cannot signal from t cell receptor, t cells cannot become activated, so then they cannot

A

provide help to b cells

138
Q

defects in antigen receptor gene rearrangemnt can result in

A

SCID

139
Q

genetic defect in thymic function that block t cell development result in

A

seere immunodeficiencies

140
Q

complete absence of thymus is very

A

rare - there is usually some thymic tissue

141
Q

repeated viral or fungal infections suggests what disorder

A

t cell

142
Q

JAk 3 deficiency results in failrue to signal through

A
interluekin receptors (2 & 7)
interluekin signal through JAK STAT pathway
143
Q

omenn syndrome results in mutations from

A

VDJ recombination - usually RAG 1 or RAG2

144
Q

Omenn syndrome b cell and t cells tend to be

A

autoreactive

145
Q

describe RAG1 and RAG2 ain omenn syndrome

A

usuallyk have some function

146
Q

mutations in TAP1 and TAP2 give rise to what syndrome

A

MHC class I defieicny

147
Q

why do mutation sin TAP1 & 2 result in MHC1 def.

A

don’t get peptide binding to class I

148
Q

MHC1 deficiency is calls

A

bare lymphocyte syndrome 1

149
Q

BLS stands for

A

Bare Lymphocyte Syndrome (BLS) Type I

150
Q

in BLS there is no

A

MHC class I

151
Q

most common mutations in BLS

A

TAP1 and TAP2

152
Q

abnormality in BLS?

A

no CD8 T cells

153
Q

MHC I what won’t be able to respond

A

CD8 T cells

154
Q

need mHC I in thymus to allow

A

cells to be selected that can bind to MHCI

155
Q

review endogenous pathway, MHC I, positive selection< CD8 T cells

A

block 2 ppt 6 pg 39

156
Q

BLS1 doesn’t really present with

A

increased susceptibility - they have cytotoxic t cell function - they are cytotoxic CD4 t cells

157
Q

cytotoxic t cells kill

A

virlly infected cells

through release of performin & granzymes & slower fas ligand patway

158
Q

how do cytotoxic t cells kill

A

release perforin & granzymes

159
Q

in absence of CD4 t cell will get

A

SCID

160
Q

increased susceptibility to what in CD4 deficiency

A

all pathogens

161
Q

failure to express MHC II results in what disease

A

Bare Lymphocyte Syndrome Type II (BLS Type II)

162
Q

where are most mutations in MHC II for BLS type II

A

class II transactivatory and regulatory factor X genes

163
Q

failure to make MHC II results in failure to

A

failure to select CD4 t cells

164
Q

without CD4 t cells, you are not going to have

A

Ig

165
Q

BLS II is form of

A

SCID

166
Q

review exogenous pathway, HC II, positive selection, CD4 t cell

A

previous blocks yay

167
Q

CD4 t cells required for what kind of immunityt

A

cell mediated & humoral immunity

168
Q

SCIDS stands for

A

Severe Combined Immunodeficiency Syndromes (SCIDS)

169
Q

most common form of SCID

A

x linked recessive form

170
Q

withotu common gamma chain cannot signal through

A

any interleukin receptor

171
Q

what is really important receptor for t cell

A

IL-7 R

172
Q

x linked SCID is caused by what deficiency

A

common gamma chain def.

173
Q

CD45 gives rise to SCID, why?

A

need CD45 during t cell activation it activates SRC family kinases, it dephosphorylates them and activates them

174
Q

IL-7 alpha gives rise to SCID, why?

A

IL-7 to IL-7R required for t cell development

175
Q

artemis gene is component of gives rise to SCID, why?

A

VDJ recombinaze

176
Q

RAG1 or 2 mutation gives rise to SCID, why?

A

don’t have RAG1 or 2 can’t rearrange antien receptors, no b or t cells

177
Q

CD3 delta chain def. gives rise to SCID, why?

A

can’t signal through t cell receptor

178
Q

CD3 mutations will impact what

A

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

179
Q

Jak3 def. gives rise to SCID, why?

A

phenotype similar to def. of IL-7R alpha chain b/c JAK3 associated with IL receptors

180
Q

most common form of autosomal forms of SCID is

A

def. in ADA (adneosine deaminase)

181
Q

autosomal recessive SCID are due to

A

ADA or PNP deficiencies

182
Q

ADA is

A

Adenosine deaminase

183
Q

PNP is

A

Purine Nucleoside Phosphorylase

184
Q

what do all SCID have in common

A
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
185
Q

review pg 46

A

46

186
Q

you do have b cells in x linked SCID but they are

A

non functional in absence of t cell help

187
Q

ADA is required for converstion of

A

pg 50

188
Q

ADA def. is what form of SCID

A

AR

189
Q

what causes SCID in ADA def.

A

Accumulation of adenosine, deoxyadenosine, and dATP is toxic for lymphocytes.

T -, B -, NK - , ALL NEGATIVE
190
Q

what cells do you have in ADA def. form of SCID

A

T -, B -, NK - , ALL NEGATIVE

191
Q

what is phenotype of ADA def. form of SCID

A

T -, B -, NK - , ALL NEGATIVE

192
Q

PNP def. not as severe as

A

ADA

193
Q

PNP def. not as severe as ADA why

A

it is not as toxic

194
Q

ataxia is

A

unstable gait/difficulty walking

195
Q

mutation in JAK3, what is phenotype

A

T-, B+ SCID

196
Q

CD45 def what is phenotype

A

T-, B+ SCID

197
Q

IL-7Ralpha def. what is phenotype

A

T-, B+ SCID

198
Q

CD3 gamma or CD3 epsiolon def. what is phenotype

A

T-, B+ SCID

199
Q

IL-7 is required for

A

VDJ joining

200
Q

CD45 is expressed on what

A

all WBC (leukocytes)

201
Q

without common gama chain you cannot signal through

A

IL-4, IL-7, IL-9, IL-15 and IL-21 receptors.

202
Q

x linked scid phenotype

A

T-, B+, NK-

203
Q

review pg 56, describe x linked SCID

A

56

204
Q

why can you not look at T cells on X linked SCID

A

there are none

205
Q

IL-2 induces proliferation of

A

B cells

206
Q

Th1 induces what IL

A

IL-2

207
Q

non-random inactivatio nof x chrom in carrier’s b/c

A

only t cells that have inactivated non fxl one will get to periphery

208
Q

all SCID will present with what opportunistic infection

A

thrush (candida alibcans)

209
Q

XHIGM does not arise due to mutation intrinsic to b cell lineage, mutation is in

A

t cell lineage - CD40L

210
Q

defects in CD4 T cell development can result in

A

SCID

211
Q

mutations that impact CD4T will present as

A

SCID

212
Q

BLS2 due to mutations in

A

TF required for expression of MHC II alpha dn beta chains - so not class II on surface so no selection for CD4 T cells

213
Q

most common form of SCID

A

x-SCID

214
Q

XSCID due to mutation of

A

signaling chain of IL-2 - common gamma

215
Q

individuals with x linked scid fail to develop

A

t cells

they do develop b cells but they are non functional

216
Q

IL-2Ralpha chain deletion will inhibit

A

T cell development in thymus

217
Q

ADA-SCID and PNP-SCID if they are deficienct can lead to buildup of

A

adoxyadenosine in ADA and guanine in PNP

218
Q

ADA and PNP normally expressed in

A

other cells that can detoxify them. lymphocytes can’t detoxify them. the metabolic bi-products are toxic to lymphocytes

219
Q

ADA scid differes from x linked scid b/c the individuas are

A

t cell - and b cell -

no t or b cells

220
Q

if there are defects in signaling in t cell antigen receptor it will cause

A

SCID

221
Q

CD3 required for signaling from

A

pre t cell receptor and t cell receptor

222
Q

if CD3 non functional will not pass

A

pre t cell stage

223
Q

mutation of CD3 is kind of like equivalent of

A

XLA, b/c you are stuck in pre b cell in XLA and stuck in pre t cell in CD3 mutation

224
Q

how does defect of CD45 impact TCR transduction

A

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

225
Q

JAK3 more associated with signaling through what receptors

A

cytokine receptors

226
Q

alpha chain of IL-2R also known as

A

CD25

227
Q

JAK3 kinase is associated with

A

IL-2R gamma o the common gamma chain

228
Q

if common gamam chain is ther but can’t signal through it might have what deficiency

A

JAK3

229
Q

what is phenotype of JAK defeciency

A

T-, B+, NK – same phenotype as X-linked SCID

230
Q

IL 7 binding to IL-7R in thymus does what

A

opens up t cell thymus receptor loci for rearrangemnt

231
Q

without signaling through IL-7 won’t get

A

T cell rearrangement

232
Q

common gamma chain what is CD

A

cD132

233
Q

phenotype of X linked scid and jak scid, what isi the difference in presentation

A

presentation similar but x linked only males

jak is AR males and females

234
Q

mutations in RAG-1, RAG-2, artemis could be what syndrome

A

omenn syndrome

235
Q

RAG-1, RAG-2 and artemis usually don’t knowck out function of genes, there is usually

A

still some t cells and b cells developing

236
Q

mutation sin RAG1, RAG2, artemis are components of

A

VDJ recominase

237
Q

omenn syndrom eresults from mutations where

A

rag1, rag2, artemis

238
Q

omenn syndrome is also sometimes referred to as

A

Familial reticuloendotheliosis with eosinophilia

or SCID with hypereosinophilia

239
Q

omenn has high levels of

A

eosinophils

240
Q

what is hallmark of omenn syndrome

A

high levels of eosinohpils

241
Q

in indivudlas with omenn, defect in t cell devlopment in thymus leads to

A

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

242
Q

poore negative selection in omenn b/c

A

low expression of AIRE

243
Q

why do omenn syndrom also rpesent with autoimmune disease

A

/c of low aire expression so t cells that get through can be autoreactive

244
Q

in add’n to poor negative selection, aire is also required for

A

t reg

245
Q

omenn has less t reg b/c of lack of aire, which also contributes to

A

autoimmune disease

246
Q

VDJ recombinase require

A

RAG-1, RAG-2, Tdt, Artemis

247
Q

RAG1 and RAG2 determine

A

what will recombne together - 12 23 rule

248
Q

what does artemis do

A

opens the hairpin

249
Q

withotu functional RAG1 and RAG2 will not get

A

VDJ recombination

250
Q

without functional artemis will not get

A

VDJ recombination

251
Q

2% of lymphocytes are in blood the rest are in

A

secondary lymphoid tissue

252
Q

more t cells or b cells in peripheral blood

A

t cells

253
Q

how does omenn syndrome present

A

rash due to type 1 hypersensitivity response b/c of elevated IGE

254
Q

what will you find in blood test for omenn syndrome

A

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

255
Q

failure to develop thymus give rse to

A

SCID

256
Q

Classic thymic function defect

A

DiGeorge syndrome

257
Q

complete DiGeorge is extremely

A

rare

258
Q

definition f DiGeorge syndrome

A

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).

259
Q

immune defiict of DiGeorge is due to

A

hypoplasia or aplasia of thymus

260
Q

due to effects on parathyroid pts with DiGeorge syndrome pts will often have

A

neonatal hypocalcemia

261
Q

if there is thymic aplasia increased susceptiblity to

A

infection due to deficit of t cells

262
Q

what beside thymus is affected by digeorge syndrome

A

cardiac defects

263
Q

what is MOI for digeorge syndrome

A

AD

264
Q

most digeroge resuts from what deletion

A

22q11

265
Q

depending on deletion in digeorge determiens

A

severity of disease - might have just a little hypoplasia of thymus

266
Q

how can digeorge syndrome present

A

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)

267
Q

if there is impact on t cel development in digeorge there will be

A

chronic infection with what t cells are involved with:viral, bacterial, fungal or protozoal organisms

268
Q

if t cell development severly impacted pts with digeorge will present with

A

opportunistic infections like thrush, pneumonia

269
Q

thymic aplasia what is treatment for digeorge

A

thymic transplant

270
Q

look at thymic shadow vs. non in digeorge

A

pg 71

271
Q

review pg 73

A

73

272
Q

deficiency in IFN gamma receptor

A

The normal pathways for host defense against intracellular bacteria are pinpointed by genetic deficiencies of IFN- and IL-12 and their receptors.

273
Q

IFN gamma important for

A

controlling intracellular bacterial infections (like TB and leprae)

274
Q

defects in IFN gamma receptor or one chain of IL-12 are susceptible to what

A

intracellular bacterial infections & fungal infections

275
Q

XLP stands for

A

X-linked lymphoproliferative syndrome

276
Q

XLP what is impacted?

A

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

277
Q

Hemophagocytic lymphohistiocytosis is characterized by? (part of XLP)

A

activated macrophages engulfing RBC

278
Q

what kind of virus often causes problems with XLP

A

epstein-barr virus

279
Q

where is defect in XLP

A

SH2D1A

280
Q

in absence of SLAM associated protein do not get efficient

A

differentiatoin into cytotoxic t cells - which are main cells that control EBV infection

281
Q

what are main cells to control EBV infection

A

cytotoxic t cells

282
Q

WAS stands for

A

Wiskott-Aldrich Syndrome

283
Q

AT stands for

A

Ataxia-Telangiectasia

284
Q

gene mtuated in WAS

A

WASP

285
Q

WASP important for

A

reorganization of cytoskeleton, esp for t cells b/c they have to reorganize their cytoskeleton to help other cells

286
Q

cytoskeletal reoganization required for

A

migration

287
Q

impaired chemotaxis of phagocytes in

A

WAS

288
Q

AT mutation that impact

A

double stranded DNA repair

289
Q

enzymes of double stranded DNA repair in AT are invovled in

A

VDJ recombination

290
Q

WAS classically presents with “classic triad”:

A

thrombocytopenia
severe eczema (by one year of age)
recurrent pyogenic infections, bloody diarrhea

291
Q

recurrent pyogenic infections due to what in WAS

A

inability o ft cell to provide help to b cell to opsonize bacteria

292
Q

severe eczema in WAS due to

A

hypersensitivity response - they ahve elevated levels of IgE

293
Q

why do pts with WAS have high IgE

A

do’nt know :(

294
Q

b/c t cells cannot provide help to b cells in WAS suseptibility to infections by

A

encapsulated bacteria

295
Q

treatment for WAS

A

BMT

296
Q

what is mOI for WASP

A

x linked recessive

297
Q

female carriers of WAS exhibit

A

skewe or non-random x chrom. inactivation

298
Q

Where is WASp expressed

A

all white blood cells and megakaryocytes

299
Q

what is the HSR in excema for WAS

A

tyep I HSR

300
Q

gene impacted in AT

A

ATM gene

301
Q

main features of AT

A
unstable gait (ataxia)
dilation of vessels in eye
recurrent infections (respiratory and sinus)
302
Q

unusual feature of AT is:

A

strongly associated with IgA deficiency

303
Q

what kind of deficiency is very common in pts with AT

A

IgA def.

304
Q

high rate of what disease in pts with AT

A

leukemia & lymphoma

305
Q

what is MOI for AT

A

AR

306
Q

most individuals with AT have elevated serum levels of

A

alpha fetoprotein

307
Q

what is serum test tosee if pt has AT

A

alpha fetoprotein

308
Q

what is often test to see if pt has AT

A

radiation - they are very suseptible to breaks in chrom. due to radiation

309
Q

BLS 1 impacts class I expression where

A

all cells on body (MHC 1 is everywhere)

310
Q

review pg 84

A

84

311
Q

review pg 85

A

85

312
Q

review pg 86

A

86