immunologic disorders Flashcards
1
Q
HAE genetics
A
AD, C1 inhibitor gene SERPING1 on chromosome 11
2
Q
rash associated with HAE type 1 and 2
A
erythema marginatum
3
Q
HAE with low C4 and low C1INH function and level
A
type 1
4
Q
HAE with low C4 and C1INH function with normal to high C1INH level
A
type 2
5
Q
decreased in all acute HAE attacks
A
C2
6
Q
these complement components are only low in acquired C1-INH deficiency
A
C1q and C3
7
Q
how do attenuated androgens help HAE
A
induce hepatic synthesis of C1 INH
8
Q
HAE treatment increases PTT
A
plasma kalikrein ihnhibitors (ecallantide and lanadelumab0
9
Q
congenital neutropenia AD mutation
A
elastase
10
Q
XLA gene
A
BTK
11
Q
hyper IgM phenotype with no germinal centers
A
CD40L deficiency
12
Q
hyper IgM phenotype with no T cell defect, have germinal centers
A
AID deficiency
13
Q
SCID T- B- NK- (3 types)
A
ADA deficiency (deaf), activated Rac2 defect, reticular dysgenesis
14
Q
SCID T- B+ NK-
A
IL2RG gene (yc deficiency) and Jak3 deficiency; note B cells present but not functional
15
Q
SCID T-B+ NK+
A
IL7Ralpha, CD3 epsilon (no gamma delta T cells), CD45, coronoin-1A deficiency
16
Q
T-B- NK+
A
cernunnos/XLF deficiency (microcephaly, bird like face); Artemis/DCLRE1C deficiency (no microcephaly)
17
Q
has 13x more ADA than anywhere else in body
A
thymus
18
Q
ADA deficiency mechansim
A
excess dATP inhibits ribonucleotide reducatase
19
Q
missense mutations in RAG genes, erythroderma (T cells go to skin), FTT, protracted diarrhea, enlargement of spleen liver lymph nodes, Eosinophilia with lack of B cells but enlarged lymph nodes (proliferation of oligoclonal T cells)
A
Omenn syndrome
20
Q
STAT3 LOF
A
Hyper IgE type 1/Job
21
Q
AD phagocytic cell disorder with increased susceptibility to Mycobacteria, low B, NK and monocytes
A
GATA2 deficiency
22
Q
complement deficiency inherited X-linked (rest AD)
A
properdin deficiency
23
Q
2 diseases with normal CH50 but absent AH50
A
properdin deficiency and Factor D deficiency
24
Q
associated with HSV encephalitis
A
TLR3 deficiency (TLR3, TRAF3, TRIF, TBK1, UNC93B1)
25
TLR3,7,8,9 recognize -
viruses
26
TLR 1, 2, 4, 5, and 6 recognize
extracellular microbial components
27
mature T cells in absence of costimulation
anergy
28
T cell suppression mechanism
activated T cells express CTLA-4 and PD-1 after prolonged stimulation
29
T cells encounter that encounter self-antigen without costimulation, mitochondrial pathway
pro-apoptotic protein Bcl-2-like protein 11 (Bim) pathway, deleted
30
T cells encounter that encounter self-antigen without costimulation, death receptor pathway
epeated T cell stimulation increases the expression of the death receptor Fas and its ligand ‘Fas-ligand’ on T cells. When adjacent T cells have engagement of Fas to Fas-ligand, apoptotic cell death occur
31
CTLA4 on activated and regulatory T cells binds
CD80 and 86 B71 and 2 (suppresses further T cell activation)
32
LFA-1 (CD11a/18) expressed on
leukocytes
33
selectins expressed on
endothelium
34
sialyl-LewisX ligands (CD15a) expressed on
leukocytes
35
integrins
LFA-1 and Mac-1
36
LAD-1
delayed umbilical cord separation; omphalitis, no pus formation; LFA-1 (CD11a), Mac-1 (CD11b), LOW cd18
37
LAD-II
no delayed umbilical cord separation; pus impaired but not absent, Bombay (hh) blood group, mutation of FUCT1 (fucosylation), absence of CD15a (sialyl lewis), short stature, developmental delayed, facial dysmorphism
38
LAD III
delayed umbilical separation, no pus, severe bleeding disorder, NORMAL CD18, CalDAG-GEF-1 mutation
39
decrease B and NK cells with monocytopenia, susceptibility to mycobacteria
GATA2 deficiency
40
IgG long half life due to
FcRN (neonatal Fc receptor)
41
bare lymphocyte syndrome
TAP protein deficiency
42
receptor and ligand that activate and maintain memory and effector T cells
ICOS and ICOS-ligand
43
recptor and ligand to activate naive T cells
CD28 on T cells plus B71,2 (CD80,86) on APCs
44
p-i concept
medication directly interacts with either the major histocompatibility complex (MHC) molecule or the T-cell receptor (TCR) molecule to stimulate an immune response. These hypersensitivity responses are primarily T-cell mediated rather than antibody mediated reactions. In addition, they do not require a sensitization phase and therefore can occur with the first exposure to the drug.
45
aspirin exacerbated respiratory disease or vancomycin induced “red man syndrome” due to activation of Mas-related G-protein coupled receptor X2 (MTGPRX2) and subsequent mast-cell degranulation.
"pseudo allergic reaction"
46
FcγRIIIA
expressed on the NK cell which mediates antibody-dependent cell-mediated cytotoxicity
47
cytokines for class switching to IgE
IL-4 and IL-13 (IL-5 class switch to IgA)
48
generalized erythroderma, scaly rash, generalized lymphadenopathy, hepatosplenomegaly and chronic diarrhea, increased CD45RO+
Omenn's syndrome
49
functionally like Th2 cells but lack T cell antigen receptors. secrete IL-4, IL-5, IL-9, IL-13, and GM-CSF
ILC2 cells
50
ILC2s express
GATA3
51
coreceptor is expressed on B cells and facilitates the binding of the B cells to the microbe to enhance B-cell receptor (BCR) signaling that leads to proliferation and differentiation of B cells.
CR2/CD21 recognizes the complement breakdown products of C3b (iC3b, C3d, and C3dg) covalently bonded to the microbial antigen.
52
B cells engage with microbes through 2 receptors
CR2/CD21 and BCR
53
During an immune response, eosinophils are recruited to the site of tissue inflammation by
chemokine eotaxin-1 (CCL11) which binds to the chemokine receptor CCR3 expressed on the eosinophils
54
In T-dependent B-cell activation, which of the following receptor and ligand interactions induces B-cell proliferation and differentiation?
interaction of CD40 expressed on B cells and CD40L expressed on the T cells induces B-cell activation and differentiation
55
lipid mediators produced by mast cells
PGD2, LTB4,C4,D4,E4
56
lipid mediators produced by eosinophils
PGE2, LTC4,D4,E4
57
primary granules eosinophils
charcot leyden crystals
58
neutrophil chemokine that promotes migration
IL-8
59
gain of function mutation in CXCR4
WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, where patients develop peripheral neutropenia because of accumulation of mature neutrophils in the bone marrow (myelokathexis).
60
transcription factor is most associated with T helper type 2 (TH2) cells?
STAT6 and GATA3
61
transcription factor associated with Th1 cells
STAT4 and Tbet
62
transcription factor associated with th17 cells
RORgammaT, STAT3
63
Transcription factors Treg
FOXP3, STAT5
64
chemokine associated with mast cell, eosinophil and basophil recruitment
CCR3
65
IgG autoantibodies to desmoglein 1 and 3, nikolsky sign, flaccid>tense bullae,
pemphigus vulgaris
66
urticaria-like pruritic skin lesions that progress to tense blisters, IgG to BP180 and BP230
bullous pemphigoid
67
antigen sampling cells in the GALT
M (microfold) cells
68
chronic urticarial rash which may bruise or become purpuric and hypocomplementemia. Minor manifestations include a biopsy which demonstrates a leukocytoclastic vasculitis; arthralgia and/or arthritis; uveitis, episcleritis, and /or conjunctivitis; proteinuria, hematuria, renal insufficiency, and/or glomerulonephritis; abdominal pain, nausea, vomiting, and/or diarrhea; and positive Anti-C1q antibodies; COPD 50%
HUVS
69
hair stylist contact derm
Paraphenylenediamine
70
initial screening test to detect homozygous deficiencies in the classical complement pathway
CH50
71
any homozygous deficiency of one of the classical complement components results in an undetectable
CH50
72
slightly low CH50
heterozygous C2 deficiency
73
major criteria for SM
biopsy with multifocal dense infiltrates of mast cells (>15 mast cells in aggregate)
74
hyper IgE syndrome with low TRECs, lymphocytopenic
AR-DOCK8
75
hyper IgE with pneumatocele, coarse facial features, delayed teeth, connective tissue sequelae
STAT3 AD/JOb
76
periodic fevers lasting 12-72 hours associated with abdominal pain, chest pain, arthritis, or rash. main long-term concern is the development of amyloidosis in about 10% of patients
FMF- mutation of MEFV gene coding for pyrin, AR, colchicine treatment of choice
77
vaccine with egg
yellow fever
78
vaccine with gelatin
MMR, varicella zoster, rabies, yellow fever
79
vaccine with yeast
hep B
80
most common genetic abnormality in PCD
DNAH5 gene mutations on chromosome 5p15.2 cause approximately 50% of outer dynein arm defects
81
treatment for MCAS with elevated urinary 11B-PGF2alpha
aspirin
82
APS-1/APECED
AIRE gene mutation, lymphocytes not deleted or tolerized to endocrine self-antigen
83
IPEX syndrome
Fox p3 mutation
84
T reg CD m arkers
CD4, CD25
85
cytokines for T reg survival
IL-2 and TGF beta
86
intrinsic mitochondrial apoptosis
activated Bim binds Bax and Bak which oligermize and insert into outer mitochondrial membrance (used by B and T cells)
87
extrinsic apoptosis pathway
Fas:FasL signals through the caspase system
FasL(CD95) upregulated on repeatedly activated T cells
88
ALPS mutation
mutation in Fas or caspase 10, lymphocytes dont' know when to die LAD, spleomegaly, lymphoma, and lack of tolerance can produce autoimmunity (cytopenia) double nefative T cells
89
earliest B cell lineage the produces Ig
pre-B cell
90
most variable part of Ig molecule
CDR3
91
Ig subtype that fixes complement most effectively
IgM
92
shortest half life of all IgG subclasses
IgG3
93
IgE that binds with highest affinity
IgE
94
IG with highest total body concentration
IgA
95
ig wtih highest plasma concentration
IgG
96
changes Ig from transmembrane to secretory form (doesn't change antigen specificity)
alternative splicing
97
stimulates isotype switching to IgA
TGFbeta and IL-5
98
dominant antibody in breast milk
IgA
99
receptor that explains long half life of IgG
FcRn found on phocyte cellular membranes
100
VDJ recombination creates
TCR diversity
101
components of TCR complex
TCR, CD3, and two zeta chains , ITAMs required for signal transduction
102
T cells that are not HLA restricted
gamma delta T cells
103
antigen NKT cells recognize
lipids in context of CD1
104
T cell receptor that binds B71, 2 (CD80 and 86)
CD28
105
most important cytokine produced during T cell activation is
IL-2 and CD25
106
disorder where cannot organize immunologic synapse and polarize T cells
WAS
107
effector T cells CD marker
CD45RA
108
memory T cells CD marker
CD45RO
109
APC and T cell co stim receptors involved in class swtiching
ICOSL and ICOS (T) and CD40 and CD40L (T)
110
SCID with no CD8 cells and no T lymphocyte function but normal B and NK cells
Zap-70 deficiency (associated with CD3 zeta chains) and phosphorylates ITAMs
111
BCR components
Igalpha beta heterodimer, CD19, CR2 (CD21), CD81 (TAPA-1)
112
CCL11
eotaxin
113
inability to encode the beta subunit of LFA-1 and MAC-1. It is an autosomal recessive inherited deficiency in the CD18 gene
type 1 LAD
114
Lack of the Golgi GDP-fructose transporter needed to express the carbohydrate ligands for E- selectin and P-selectin
type 2 LAD
115
protein that binds S1PR1 and reduces its cell surface expression. This prevents the naïve T cell from migrating from the lymph node to the blood, where the concentration of S1P is higher.
CD69
116
promotes the movement of B cells into the white pulp in response to CXCL13
CXCR5
117
plays a critical role in dendritic cell migration into the lymph nodes and is expressed at high levels on naïve T-cells to promote their interaction?
CCR7
118
cellular membrane TLRs
1, 2, 4, 5, 6.
119
genetic deficincy in UNC93b results in
HSV encephalitis; NC-93B is a protein on the endoplasmic reticulum required for endosomal localization and proper function of TLR 3, 7, 8 and 9.
120
used to treat cryopyrin-associated periodic syndrome (CAPS)
Muckle-Wells, NOMID, FCAS are due to a mutation in NLRP3 (aka cryopyrin),
IL-1 and IL-1R antagonists, canakinumab and anakinra respectively, can be used to treat these disorders as IL-1 is generated from pro-IL-1β in the NLRP3 inflammasome.
121
flexibility of the antibody is mainly due to the hinge regions located between ***domains, which permit independent movement of antigen binding sites relative to the rest of the molecule.
CH1 and 2 domains
122
where in lymph node does affinity maturation occur
germinal center
123
increases expression of FcγRIIB and binds to this receptor. It delivers inhibitory signals to B lymphocytes and myeloid cells leading to decreased antibody production and dampened inflammation.
IVIG
124
Chemokines work through
GPCRs
125
increases eosinophil apoptosis
IL-4
126
eosinophil primary granule
Charcot Leyden crystal
127
used to detect presence of eosionophils in tissue even when not seen on biopsy
major basic protein
128
stimulates eosinophils
GMCSF, IL-3, IL-5
129
eosinophil transcription factor
GATA1
130
eosinophils migrate to tissue in response to
RANTES (CCL-5_ and eotaxin (CCL-11, CCL-24)
131
immune deficiency with eosinophilia
hyper IgE syndrome, Omenn syndrome, FoxP3, Zap70, Netherton syndrome
132
basopihl cytokine
IL3 receptor CD123
133
monocyte CD marker
CD14 (component of TLR4 and LPS receptor)
134
highly expressed CD marker on monocytes and macrophages
CD14
135
cytokines secreted by macrophages
TNF alpha, IL-1, and IL-6
136
plasmacytoid DC marker
CD123 (no CD11, all other types have), fight viral infections
137
dendritic cells with birbeck granules
langerhans
138
GM-CSF and IL-4 stimulate
dendritic cells
139
attracts neutrophils to tisseu
IL-8 (CXCL8) and LTB4
140
neutrophil primary granules enlarged
Chediak Higashi syndrome
141
